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ISO 14644 Complete

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ISO 14644 Cleanrooms and Associated Controlled Environments (Parts 1, 5, 7): Classification, Operations, and Separative Devices

Source: ISO 14644-1 Version 2015.pdf Pages: 44

--- PAGE 1 --- © ISO 2015 Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration Salles propres et environnements maîtrisés apparentés — Partie 1: Classification de la propreté particulaire de l’air INTERNATIONAL STANDARD ISO 14644-1 Second edition 2015-12-15 Reference number ISO 14644-1:2015(E) Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 2 ---  ISO 14644-1:2015(E)  ii © ISO 2015 – All rights reserved COPYRIGHT PROTECTED DOCUMENT © ISO 2015, Published in Switzerland All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of the requester. ISO copyright office Ch. de Blandonnet 8 • CP 401 CH-1214 Vernier, Geneva, Switzerland Tel. +41 22 749 01 11 Fax +41 22 749 09 47 copyright@iso.org www.iso.org Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 3 ---  ISO 14644-1:2015(E)  Foreword.........................................................................................................................................................................................................................................iv Introduction..................................................................................................................................................................................................................................v Scope..................................................................................................................................................................................................................................1 Normative references.......................................................................................................................................................................................1 Terms and definitions......................................................................................................................................................................................1 3.1 General........................................................................................................................................................................................................... 1 3.2 Airborne particles................................................................................................................................................................................. 2 3.3 Occupancy states................................................................................................................................................................................... 3 3.4 Testing instrumentation (see Annex F).............................................................................................................................. 3 3.5 Instrument specifications.............................................................................................................................................................. 4 Classification.............................................................................................................................................................................................................4 4.1 Occupancy state(s)............................................................................................................................................................................... 4 4.2 Particle size(s)......................................................................................................................................................................................... 4 4.3 ISO Class number................................................................................................................................................................................... 4 4.4 Designation................................................................................................................................................................................................. 5 4.5 Intermediate decimal cleanliness classes and particle size thresholds.................................................5 Demonstration of compliance.................................................................................................................................................................6 5.1 Principle........................................................................................................................................................................................................ 6 5.2 Testing............................................................................................................................................................................................................. 6 5.3 Airborne particle concentration evaluation................................................................................................................... 6 5.4 Test report................................................................................................................................................................................................... 6 Annex A (normative) Reference method for classification of air cleanliness by particle concentration.....................................................................................................................................................................................8 Annex B (informative) Examples of classification calculations.............................................................................................13 Annex C (informative) Counting and sizing of airborne macroparticles......................................................................22 Annex D (informative) Sequential sampling procedure................................................................................................................27 Annex E (informative) Specification of intermediate decimal cleanliness classes and particle size thresholds...............................................................................................................................................................................34 Annex F (informative) Test instruments........................................................................................................................................................36 Bibliography..............................................................................................................................................................................................................................37 © ISO 2015 – All rights reserved iii Contents Page Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 4 ---  ISO 14644-1:2015(E) Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives). Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of any patent rights identified during the development of the document will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents). Any trade name used in this document is information given for the convenience of users and does not constitute an endorsement. For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information The committee responsible for this document is ISO/TC  209, Cleanrooms and associated controlled environments. This second edition cancels and replaces the first edition (ISO  14644-1:1999), which has been technically revised throughout. ISO 14644 consists of the following parts, under the general title Cleanrooms and associated controlled environments: — Part 1: Classification of air cleanliness by particle concentration — Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration — Part 3: Test methods — Part 4: Design, construction and start-up — Part 5: Operations — Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) — Part 8: Classification of air cleanliness by chemical concentration (ACC) — Part 9: Classification of surface cleanliness by particle concentration — Part 10: Classification of surface cleanliness by chemical concentration Attention is also drawn to ISO  14698, Cleanrooms and associated controlled environments  — Biocontamination control: — Part 1: General principles and methods — Part 2: Evaluation and interpretation of biocontamination data  iv © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 5 ---  ISO 14644-1:2015(E) Introduction Cleanrooms and associated controlled environments provide for the control of contamination of air and, if appropriate, surfaces, to levels appropriate for accomplishing contamination-sensitive activities. Contamination control can be beneficial for protection of product or process integrity in applications in industries such as aerospace, microelectronics, pharmaceuticals, medical devices, healthcare and food. This part of ISO 14644 specifies classes of air cleanliness in terms of the number of particles expressed as a concentration in air volume. It also specifies the standard method of testing to determine cleanliness class, including selection of sampling locations. This edition is the result of a response to an ISO Systematic Review and includes changes in response to user and expert feedback validated by international enquiry. The title has been revised to “Classification of air cleanliness by particle concentration” to be consistent with other parts of ISO 14644. The nine ISO cleanliness classes are retained with minor revisions. Table 1 defines the particle concentration at various particle sizes for the nine integer classes. Table E.1 defines the maximum particle concentration at various particle sizes for intermediate classes. The use of these tables ensures better definition of the appropriate particle-size ranges for the different classes. This part of ISO  14644 retains the macroparticle descriptor concept; however, consideration of nano-scale particles (formerly defined as ultrafine particles) will be addressed in a separate standard. The most significant change is the adoption of a more consistent statistical approach to the selection and the number of sampling locations; and the evaluation of the data collected. The statistical model is based on adaptation of the hypergeometric sampling model technique, where samples are drawn randomly without replacement from a finite population. The new approach allows each location to be treated independently with at least a 95 % level of confidence that at least 90 % of the cleanroom or clean zone areas will comply with the maximum particle concentration limit for the target class of air cleanliness. No assumptions are made regarding the distribution of the actual particle counts over the area of the cleanroom or clean zone; while in ISO  14644-1:1999 an underlying assumption was that the particle counts follow the same normal distribution across the room, this assumption has now been discarded to allow the sampling to be used in rooms where the particle counts vary in a more complex manner. In the process of revision it has been recognized that the 95 % UCL was neither appropriate nor was applied consistently in ISO 14644-1:1999. The minimum number of sampling locations required has been changed, compared with ISO 14644-1:1999. A reference table, Table A.1, is provided to define the minimum number of sampling locations required based on a practical adaptation of the sampling model technique. An assumption is made that the area immediately surrounding each sampling location has a homogeneous particle concentration. The cleanroom or clean zone area is divided up into a grid of sections of near equal area, whose number is equal to the number of sampling locations derived from Table A.1. A sampling location is placed within each grid section, so as to be representative of that grid section. It is assumed for practical purposes that the locations are chosen representatively; a “representative” location (see A.4.2) means that features such as cleanroom or clean zone layout, equipment disposition and airflow systems should be considered when selecting sampling locations. Additional sampling locations may be added to the minimum number of sampling locations. Finally, the annexes have been reordered to improve the logic of this part of ISO 14644 and portions of the content of certain annexes concerning testing and test instruments have been included from ISO 14644-3:2005. The revised version of this part of ISO  14644 addresses the ≥  5  µm particle limits for ISO Class 5 in the sterile products annexes of the EU, PIC/S and WHO GMPs by way of an adaptation of the macroparticle concept. The revised version of this part of ISO 14644 now includes all matters related to classification of air cleanliness by particle concentration. The revised version of ISO 14644-2:2015 now deals exclusively with the monitoring of air cleanliness by particle concentration. Cleanrooms may also be characterized by attributes in addition to the classification of air cleanliness by particle concentration. Other attributes, such as air cleanliness in terms of chemical concentration, may  © ISO 2015 – All rights reserved v Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 6 ---  ISO 14644-1:2015(E) be monitored and the attribute’s grade or level may be designated along with the classification of the ISO Class of cleanliness. These additional attributes do not suffice alone to classify a cleanroom or clean zone.  vi © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 7 ---  INTERNATIONAL STANDARD ISO 14644-1:2015(E) Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration 1 Scope This part of ISO 14644 specifies the classification of air cleanliness in terms of concentration of airborne particles in cleanrooms and clean zones; and separative devices as defined in ISO 14644-7. Only particle populations having cumulative distributions based on threshold (lower limit) particle sizes ranging from 0,1 µm to 5 µm are considered for classification purposes. The use of light scattering (discrete) airborne particle counters (LSAPC) is the basis for determination of the concentration of airborne particles, equal to and greater than the specified sizes, at designated sampling locations. This part of ISO 14644 does not provide for classification of particle populations that are outside the specified lower threshold particle-size range, 0,1  µm to 5  µm. Concentrations of ultrafine particles (particles smaller than 0,1  µm) will be addressed in a separate standard to specify air cleanliness by nano-scale particles. An M descriptor (see Annex  C) may be used to quantify populations of macroparticles (particles larger than 5 µm). This part of ISO 14644 cannot be used to characterize the physical, chemical, radiological, viable or other nature of airborne particles. 2 Normative references The following documents, in whole or in part, are normatively referenced in this document and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 14644-2:2015, Cleanrooms and associated controlled environments — Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration ISO 14644-7, Cleanrooms and associated controlled environments — Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) 3 Terms and definitions For the purposes of this document, the following terms and definitions apply.

3.1 General

3.1.1 cleanroom room within which the number concentration of airborne particles is controlled and classified, and which is designed, constructed and operated in a manner to control the introduction, generation and retention of particles inside the room Note 1 to entry: The class of airborne particle concentration is specified. © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 8 ---  ISO 14644-1:2015(E) Note 2 to entry: Levels of other cleanliness attributes such as chemical, viable or nanoscale concentrations in the air, and also surface cleanliness in terms of particle, nanoscale, chemical and viable concentrations might also be specified and controlled. Note  3  to entry:  Other relevant physical parameters might also be controlled as required, e.g. temperature, humidity, pressure, vibration and electrostatic. 3.1.2 clean zone defined space within which the number concentration of airborne particles is controlled and classified, and which is constructed and operated in a manner to control the introduction, generation and retention of contaminants inside the space Note 1 to entry: The class of airborne particle concentration is specified. Note 2 to entry: Levels of other cleanliness attributes such as chemical, viable or nanoscale concentrations in the air, and also surface cleanliness in terms of particle, nanoscale, chemical and viable concentrations might also be specified and controlled. Note 3 to entry: A clean zone(s) can be a defined space within a cleanroom or might be achieved by a separative device. Such a device can be located inside or outside a cleanroom. Note  4  to entry:  Other relevant physical parameters might also be controlled as required, e.g. temperature, humidity, pressure, vibration and electrostatic. 3.1.3 installation cleanroom or one or more clean zones, together with all associated structures, air-treatment systems, services and utilities 3.1.4 classification method of assessing level of cleanliness against a specification for a cleanroom or clean zone Note 1 to entry: Levels should be expressed in terms of an ISO Class, which represents maximum allowable concentrations of particles in a unit volume of air.

3.2 Airborne particles

3.2.1 particle minute piece of matter with defined physical boundaries 3.2.2 particle size diameter of a sphere that produces a response, by a given particle-sizing instrument, that is equivalent to the response produced by the particle being measured Note 1 to entry: For discrete-particle light-scattering instruments, the equivalent optical diameter is used. 3.2.3 particle concentration number of individual particles per unit volume of air 3.2.4 particle size distribution cumulative distribution of particle concentration as a function of particle size 3.2.5 macroparticle particle with an equivalent diameter greater than 5 µm  2 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 9 ---  ISO 14644-1:2015(E)

3.2.6 M descriptor

designation for measured or specified concentration of macroparticles per cubic metre of air, expressed in terms of the equivalent diameter that is characteristic of the measurement method used Note 1 to entry: The M descriptor can be regarded as an upper limit for the averages at sampling locations. M descriptors cannot be used to define ISO Classes, but the M descriptor may be quoted independently or in conjunction with ISO Classes. 3.2.7 unidirectional airflow controlled airflow through the entire cross-section of a cleanroom or a clean zone with a steady velocity and airstreams that are considered to be parallel 3.2.8 non-undirectional airflow air distribution where the supply air entering the cleanroom or clean zone mixes with the internal air by means of induction

3.3 Occupancy states

3.3.1 as-built condition where the cleanroom or clean zone is complete with all services connected and functioning but with no equipment, furniture, materials or personnel present 3.3.2 at-rest condition where the cleanroom or clean zone is complete with equipment installed and operating in a manner agreed upon, but with no personnel present 3.3.3 operational agreed condition where the cleanroom or clean zone is functioning in the specified manner, with equipment operating and with the specified number of personnel present 3.4 Testing instrumentation (see Annex F) 3.4.1 resolution smallest change in a quantity being measured that causes a perceptible change in the corresponding indication Note 1 to entry: Resolution can depend on, for example, noise (internal or external) or friction. It may also depend on the value of a quantity being measured. [SOURCE: ISO/IEC Guide 99:2007, 4.14] 3.4.2 maximum permissible measurement error extreme value of measurement error, with respect to a known reference quantity value, permitted by specifications or regulations for a given measurement, measuring instrument, or measuring system Note 1 to entry: Usually, the term “maximum permissible errors” or “limits of error” is used where there are two extreme values. Note 2 to entry: The term “tolerance” should not be used to designate “maximum permissible error”. [SOURCE: ISO/IEC Guide 99:2007, 4.26]  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 10 ---  ISO 14644-1:2015(E)

3.5 Instrument specifications

3.5.1 LSAPC

light scattering airborne particle counter light scattering discrete airborne particle counter instrument capable of counting and sizing single airborne particles and reporting size data in terms of equivalent optical diameter Note 1 to entry: The specifications for the LSAPC are given in ISO 21501-4:2007. 3.5.2 discrete-macroparticle counter instrument capable of counting and sizing single airborne macroparticles Note 1 to entry: See Table F.1 for specifications. 3.5.3 time-of-flight particle sizing apparatus discrete-particle counting and sizing apparatus that defines the aerodynamic diameter of particles by measuring the time for a particle to accommodate to a change in air velocity Note  1  to entry:  This is usually done by measuring the particle transit time optically after a fluid stream velocity change. Note 2 to entry: See Table F.2 for specifications. 4 Classification 4.1 Occupancy state(s) The air cleanliness class by particle concentration of air in a cleanroom or clean zone shall be defined in one or more of three occupancy states, viz. “as-built,” “at-rest” or “operational” (see 3.3). 4.2 Particle size(s) One, or more than one, threshold (lower limit) particle sizes situated within the range from ≥0,1 µm to ≥5 µm are to be used to determine air cleanliness particle concentration for classification.

4.3 ISO Class number

Air cleanliness class by particle concentration shall be designated by an ISO Class number, N. The maximum permitted concentration of particles for each considered particle size is determined from Table 1. Particle number concentrations for different threshold sizes in Table 1 do not reflect actual particle size and number distribution in the air and serve as criteria for classification only. Examples of classification calculations are included in Annex B.  4 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 11 ---  ISO 14644-1:2015(E) Table 1 — ISO Classes of air cleanliness by particle concentration ISO Class number (N) Maximum allowable concentrations (particles/m3) for particles equal to and greater than the considered sizes, shown belowa 0,1 µm 0,2 µm 0,3 µm 0,5 µm 1 µm 5 µm 10b d d d d e 24b 10b d d e 1 000 35b d e 10 000 2 370 1 020 83b e 100 000 23 700 10 200 3 520 d, e, f 1 000 000 237 000 102 000 35 200 8 320 c c c 352 000 83 200 2 930 c c c 3 520 000 832 000 29 300 9g c c c 35 200 000 8 320 000 293 000 a All concentrations in the table are cumulative, e.g. for ISO Class 5, the 10 200 particles shown at 0,3 µm include all particles equal to and greater than this size. b These concentrations will lead to large air sample volumes for classification. Sequential sampling procedure may be applied; see Annex D. c Concentration limits are not applicable in this region of the table due to very high particle concentration. d Sampling and statistical limitations for particles in low concentrations make classification inappropriate. e Sample collection limitations for both particles in low concentrations and sizes greater than 1 μm make classification at this particle size inappropriate, due to potential particle losses in the sampling system. f In order to specify this particle size in association with ISO Class 5, the macroparticle descriptor M may be adapted and used in conjunction with at least one other particle size. (See C.7.) g This class is only applicable for the in-operation state.

4.4 Designation

The designation of airborne particle concentration for cleanrooms and clean zones shall include a) the ISO Class number, expressed as “ISO Class N”, b) the occupancy state to which the classification applies, and c) the considered particle size(s). If measurements are to be made at more than one considered particle size, each larger particle diameter (e.g. D2) shall be at least 1,5 times the next smaller particle diameter (e.g. D1), i.e. D2 ≥ 1,5 × D1. EXAMPLE ISO Class number; occupancy state; considered particle size(s) ISO Class 4; at rest; 0,2 µm, 0,5 µm

4.5 Intermediate decimal cleanliness classes and particle size thresholds

Where intermediate classes, or intermediate particle size thresholds for integer and intermediate classes are required, refer to informative Annex E.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 12 ---  ISO 14644-1:2015(E) 5 Demonstration of compliance

5.1 Principle

Compliance with air cleanliness (ISO Class) requirements specified by the customer is verified by performing specified testing procedures and by providing documentation of the results and conditions of testing. At-rest or operational classification may be performed periodically based upon risk assessment of the application, typically on an annual basis. For monitoring cleanrooms, clean zones and separative devices, ISO 14644-2:2015 shall be used. NOTE Where the installation is equipped with instrumentation for continuous or frequent monitoring of air cleanliness by particle concentration and other parameters of performance as applicable, the time intervals between classification may be extended provided that the results of the monitoring remain within the specified limits.

5.2 Testing

The reference test method for demonstrating compliance is given in Annex A (normative). Alternative methods or instrumentation (or both), having at least comparable performance, may be specified. If no alternative is specified or agreed upon, the reference method shall be used. Tests performed to demonstrate compliance shall be conducted using instruments which are in compliance with calibration requirements at the time of testing.

5.3 Airborne particle concentration evaluation

Upon completion of testing in accordance with Annex A, the concentration of particles (expressed as number of particles per cubic metre) in a single sample volume at each sampling location shall not exceed the concentration limit(s) given in Table 1 or Table E.1 for intermediate decimal classes for the considered size(s). If multiple single sample volumes are taken at a sampling location, the concentrations shall be averaged and the average concentration must not exceed the concentration limits given in Table 1 or Table E 1. Intermediate particle sizes shall be derived from Formula (E.1). Particle concentrations used for determination of compliance with ISO Classes shall be measured by the same method for all considered particle sizes.

5.4 Test report

The results from testing each cleanroom or clean zone shall be recorded and submitted as a comprehensive report, along with a statement of compliance or non-compliance with the specified designation of air cleanliness class by particle concentration. The test report shall include a) the name and address of the testing organization, and the date on which the test was performed, b) the number and year of publication of this part of ISO 14644, i.e. ISO 14644-1:2015, c) a clear identification of the physical location of the cleanroom or clean zone tested (including reference to adjacent areas if necessary), and specific designations for coordinates of all sampling locations (a diagrammatic representation can be helpful), d) the specified designation criteria for the cleanroom or clean zone, including the ISO Class number, the relevant occupancy state(s), and the considered particle size(s), e) details of the test method used, with any special conditions relating to the test, or departures from the test method, and identification of the test instrument and its current calibration certificate, and  6 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 13 ---  ISO 14644-1:2015(E) f) the test results, including particle concentration data for all sampling locations. If concentrations of macroparticles are quantified, as described in Annex C, the relevant information should be included with the test report.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 14 ---  ISO 14644-1:2015(E) Annex A (normative)

Reference method for classification of air cleanliness by particle concentration A.1 Principle A discrete-particle-counting instrument is used to determine the concentration of airborne particles, equal to and greater than the specified sizes, at designated sampling locations. A.2 Apparatus requirements A.2.1 Particle-counting instrument The instrument shall have a means of displaying or recording the count and size of discrete particles in air with a size discrimination capability to detect the total particle concentration in the appropriate particle size ranges for the class under consideration. NOTE Light scattering (discrete) airborne particle counters (LSAPC) are commonly used for undertaking air cleanliness classification. A.2.2 Instrument calibration The particle counter shall have a valid calibration certificate: the frequency and method of calibration should be based upon current accepted practice as specified in ISO 21501-4.[1] NOTE Some particle counters cannot be calibrated to all of the required tests in ISO 21501-4. If this is the case, record the decision to use the counter in the test report. A.3 Preparation for particle count testing Prior to testing, verify that all relevant aspects of the cleanroom or clean zone that contribute to its integrity are complete and functioning in accordance with its performance specification. Care should be taken when determining the sequence for performing supporting tests for cleanroom performance. ISO 14644-3, Annex A provides a checklist. A.4 Establishment of sampling locations A.4.1 Deriving the number of sampling locations Derive the minimum number of sampling locations, NL, from Table A.1. Table A.1 provides the number of sampling locations related to the area of each cleanroom or clean zone to be classified and provides at least 95 % confidence that at least 90 % of the cleanroom or clean zone area does not exceed the class limits.  8 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 15 ---  ISO 14644-1:2015(E) Table A.1 — Sampling locations related to cleanroom area Area of cleanroom (m2) less than or equal to Minimum number of sampling locations to be tested (NL) 1 000

 1 000 See Formula (A.1) NOTE 1 If the considered area falls between two values in the table, the greater of the two should be selected. NOTE 2 In the case of unidirectional airflow, the area may be considered as the cross section of the moving air perpendicular to the direction of the airflow. In all other cases the area may be considered as the horizontal plan area of the cleanroom or clean zone. A.4.2 Positioning the sampling locations In order to position the sampling locations a) use the minimum number of sampling locations NL derived from Table A.1, b) then divide the whole cleanroom or clean zone into NL sections of equal area, c) select within each section a sampling location considered to be representative of the characteristics of the section, and  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 16 ---  ISO 14644-1:2015(E) d) at each location, position the particle counter probe in the plane of the work activity or another specified point. Additional sampling locations may be selected for locations considered critical. Their number and positions shall also be agreed and specified. Additional sections and associated sampling locations may be included to facilitate subdivision into equal sections. For non-unidirectional airflow cleanrooms or clean zones, locations may not be representative if they are located directly beneath non-diffused supply air sources. A.4.3 Sampling locations for large cleanrooms or clean zones When the area of the cleanroom or clean zone is greater than 1 000 m2, apply Formula (A.1) to determine the minimum number of sampling locations required. N A L = ×       1 000 (A.1) where NL is the minimum number of sampling locations to be evaluated, rounded up to the next whole number; A is the area of the cleanroom in m2. A.4.4 Establishment of single sample volume and sampling time per location At each sampling location, sample a volume of air sufficient to detect a minimum of 20 particles if the particle concentration for the largest selected particle size were at the class limit for the designated ISO Class. The single sample volume, Vs, per sampling location is determined by using Formula (A.2): V n m s =       × 1000 C ,

(A.2) where  Vs is the minimum single sample volume per location, expressed in litres (except see Annex D); Cn,m is the class limit (number of particles per cubic metre) for the largest considered particle size specified for the relevant class; is the number of particles that could be counted if the particle concentration were at the class limit. The volume sampled at each location shall be at least 2 l, with a minimum sampling time of 1 min for each sample at each location. Each single sample volume at each sampling location shall be the same. When Vs is very large, the time required for sampling can be substantial. By using the optional sequential sampling procedure (see Annex D), both the required sample volume and the time required to obtain samples may be reduced. A.5 Sampling procedure A.5.1 Set up the particle counter (see A.2) in accordance with the manufacturer’s instructions including performing a zero count check.  10 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 17 ---  ISO 14644-1:2015(E) A.5.2 The sampling probe shall be positioned pointing into the airflow. If the direction of the airflow being sampled is not controlled or predictable (e.g. non-unidirectional airflow), the inlet of the sampling probe shall be directed vertically upward. A.5.3 Ensure normal conditions for the selected occupancy state are established before sampling. A.5.4 Sample the volume of air determined in A.4.4, as a minimum, for each sample at each sampling location. A.5.5 If an out-of-specification count is found at a location due to an identified abnormal occurrence, then that count can be discarded and noted as such on the test report and a new sample taken. A.5.6 If an out-of-specification count found at a location is attributed to a technical failure of the cleanroom or equipment, then the cause should be identified, remedial action taken and retesting performed of the failed sampling location, the immediate surrounding locations and any other locations affected. The choice shall be clearly documented and justified. A.6 Processing of results A.6.1 Recording of results Record the result of each sample measurement as the number of particles in each single sample volume at each of the considered particle size(s) appropriate to the relevant ISO Class of air cleanliness. NOTE For particle counters with a concentration calculation mode, the manual evaluation may not be necessary. A.6.1.1 Average concentration of particles at each sampling location When two or more single sample volumes are taken at a location, calculate and record the average number of particles per location at each considered particle size from the individual sample particle concentrations, according to Formula (A.3). x x x x n i i i i n

(A.3) where xi is the average number of particles at location i, representing any location; xi.1 to xi.n are the number of particles in individual samples; n is the number of samples taken at location i. A.6.1.2 Calculate the concentration per cubic metre C x V i i t

×1000

(A.4) where Ci is the concentration of particles per cubic metre; xi is the average number of particles at location i, representing each location;  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 18 ---  ISO 14644-1:2015(E) Vt is the selected single sample volume in litres. A.6.2 Interpretation of results A.6.2.1 Classification requirements The cleanroom or clean zone is deemed to have met the specified air cleanliness classification requirements if the average of the particle concentrations (expressed as number of particles per cubic metre) measured at each of the sampling locations does not exceed the concentration limits determined from Table 1. If intermediate classes or particle sizes are used, as defined in Annex E, appropriate limits derived from Table E.1 or Formula (E.1) should be used. A.6.2.2 Out-of-specification result In the event of an out-of-specification count, an investigation shall be undertaken. The result of the investigation and remedial action shall be noted in the test report (see 5.4).  12 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 19 ---  ISO 14644-1:2015(E) Annex B (informative)

Examples of classification calculations B.1 Example 1 B.1.1 A cleanroom has a floor area of 18  m2 and is specified to be ISO Class 5 in operation. The classification is to be performed using a discrete-particle counter having a flow rate of 28,3 l per minute. Two particle sizes are considered: D ≥ 0,3 µm and D ≥ 0,5 µm. The number of sampling locations, NL, is determined to be six, based on Table A.1. B.1.2 The particle concentration limits for ISO Class 5 are taken from Table 1: Cn (≥ 0,3 µm) = 10 200 particles/m3 Cn (≥ 0,5 µm) = 3 520 particles/m3 B.1.3 The required single sample volume can be calculated from Formula (A.2) as follows: V n m s =       × 1000 C , Vs =       × 1000 3520 Vs = ( )× 0 00568 1000 , Vs litres = 5 68 ,

The single sample volume has been calculated to be 5,68 l. As the LSAPC being used for this test had a flow rate of 28,3 litres per minute, a 1-min single sample count would be required (see A.4.4) and therefore 28,3 l would be sampled for each single sample volume. NOTE In A.4.4, the minimum sample volume for the procedure is set by calculating the minimum sample volume as shown above and then determining the sample volume obtained for the operation of the particle counter in the time period of 1 min. The sampling at each position must occur for at least 1 min; if the minimum sample volume as calculated is satisfied within the 1-min period, then the sampling process can be stopped at the end of 1 min. If the calculated minimum volume cannot be obtained within the 1-min period with the flow rate of the instrument to be used, then the sampling must continue for a longer time period until at least the minimum sample volume has been obtained. Because there are several possible flow rates for particle counters, users are cautioned to verify the flow rate of the specific instrument(s) to be used when determining the sampling time needed to satisfy both the 1-min requirement and the calculated minimum sample volume. B.1.4 At each sampling location only one sample volume is taken. The number of particles per cubic metre, xi, is calculated for each location and each particle size as shown in Tables B.1 and B.2.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 20 ---  ISO 14644-1:2015(E) Table B.1 — Sampling data for particles ≥ 0,3 µm Sampling location Sample 1 xi ≥ 0,3 µm (counts per 28,3 l) Location sample average (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 5 limit for 0,3 µm particle size Pass/fail 8 649 10 200 Pass 6 531 10 200 Pass 2 083 10 200 Pass 3 742 10 200 Pass 5 789 10 200 Pass 6 919 10 200 Pass Table B.2 — Sampling data for particles ≥ 0,5 µm Sampling location Sample 1 xi ≥ 0,5 µm (counts per 28,3 l) Location sample average (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 5 limit for 0,5 µm particle size Pass/fail 3 520 Pass 3 520 Pass 3 520 Pass 3 520 Pass 3 520 Pass 3 520 Pass B.1.5 Each value of the concentration for D ≥ 0,3 µm is less than the limit of 10 200 particles/m3 and D ≥ 0,5 µm is less than the limit of 3 520 particles/m3 as established in B.1.2; therefore, the air cleanliness by particle concentration of the cleanroom meets the required ISO Class. B.2 Example 2 B.2.1 A cleanroom has a floor area of 9  m2 and is specified to be ISO Class 3 in operation. The classification is to be performed using a discrete-particle counter having a flow rate of 50,0 l per minute. Only one particle size (D ≥ 0,1 µm) is considered. The number of sampling locations, NL, is determined to be five, based on Table A.1. B.2.2 The particle concentration limit for ISO Class 3 at ≥ 0,1 µm is taken from Table 1: Cn (≥ 0,1 µm) = 1 000 particles/m3 B.2.3 The required single sample volume can be calculated from Formula (A.2) as follows: V n m s =       × 1000 C , Vs =       × 1000  14 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 21 ---  ISO 14644-1:2015(E) Vs = ( )× 0 02 1000 , Vs litres = 20 0 ,

The single sample volume has been calculated to be 20,0 l. As the discrete-particle counter being used for this test had a flow rate of 50,0 l per minute, a 1-min single sample count would be required (see A.4.4) and therefore 50,0 l would be sampled for each single sample volume. B.2.4 At each sampling location only one sample volume is taken. The number of particles per cubic metre, xi, is calculated for each location and recorded in Table B.3. Table B.3 — Sampling data for particles ≥ 0,1 μm Sampling location Sample 1 xi ≥ 0,1 µm (counts per 50,0 l) Location sample average (counts per 50,0 l) Location concentration average (counts per m3 = location average × 20) ISO Class 3 limit for ≥ 0,1 µm particle size Pass/fail 1 000 Pass 1 000 Pass 1 000 Pass 1 000 Pass 1 000 Pass B.2.5 Each value of the concentration for D  ≥  0,1  µm is less than the limit of 1  000 particles/m3 established in Table 1; therefore, the air cleanliness by particle concentration of the cleanroom meets the required ISO Class. B.3 Example 3 B.3.1 A cleanroom has a floor area of 64 m2 and is specified ISO Class 5 in operation. The classification is to be performed using a discrete-particle counter having a flow rate of 28,3 l per minute. Only one particle size (D ≥ 0,5 µm) is considered. The number of sampling locations, NL, is determined to be 12, based on Table A.1. B.3.2 The particle concentration limit for ISO Class 5 at ≥ 0,5 µm is taken from Table 1: Cn (≥ 0,5 µm) = 3 520 particles/m3 B.3.3 The required single sample volume can be calculated from Formula (A.2) as follows: V n m s =       × 1000 C , Vs =       × 1000 3520 Vs = ( )× 0 00568 1000 ,  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 22 ---  ISO 14644-1:2015(E) Vs litres = 5 68 ,

The single sample volume has been calculated to be 5,68 l. As the discrete-particle counter used for this test had a flow rate of 28,3 l per minute, a 1-min single sample count would be required (see A.4.4) and therefore 28,3 l would be sampled for each single sample volume. B.3.4 At each sampling location only one sample volume is taken. The number of particles per cubic metre, xi, is calculated for each location and recorded in Table B.4. Table B.4 — Sampling data for particles ≥ 0,5 μm Sampling location Sample 1 xi ≥ 0,5 µm Location sample average concentration (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 5 limit for 0,5 µm particle size Pass/fail 1 236 3 520 Pass 3 520 Pass 3 142 3 520 Pass 1 730 3 520 Pass 3 520 Pass 2 118 3 520 Pass 3 520 Pass 1 553 3 520 Pass 2 083 3 520 Pass 1 800 3 520 Pass 3 520 Pass 1 094 3 520 Pass B.3.5 Each value of the concentration for D  =  0,5  µm is less than the limit of 3  520 particles/m3 established in Table 1; therefore, the air cleanliness by particle concentration of the cleanroom meets the required ISO Class. B.4 Example 4 B.4.1 A cleanroom has a floor area of 25  m2 and is specified to be ISO  Class 5 in operation. The classification is to be performed using a discrete-particle counter having a flow rate of 28,3 l per minute. Only one particle size (D ≥ 0,5 µm) is considered. The minimum number of sampling locations from Table A.1 is 7. B.4.2 The particle concentration limit for ISO Class 5 at ≥ 0,5 µm is obtained from Table 1 as follows: Cn (≥ 0,5 µm) = 3 520 particles/m3 B.4.3 The required single sample volume can be calculated from Formula (A.2) as follows: V n m s =       × 1000 C ,  16 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 23 ---  ISO 14644-1:2015(E) Vs =       × 1000 3520 Vs = ( )× 0 00568 1000 , Vs litres = 5 68 ,

The single sample volume has been calculated to be 5,68 l. As the discrete-particle counter being used for this test had a flow rate of 28,3 l per minute, a 1-min single sample count would be required (see A.4.4) and therefore 28,3 l would be sampled for each single sample volume. B.4.4 The number of sampling locations required from Table A.1 is 7, however, this example shows that the customer and supplier have agreed to add an additional 3 locations, making 10 in total. At each sampling location the number of single sample volumes varies from 1 to 3. B.4.5 For recording purposes, the number of particles (concentration) per cubic metre, xi, is calculated from the average count per unit volume (28,3 l) at each location (28,3 × 35,3) as in Table B.5. Table B.5 — Sampling data for particles ≥ 0.5 μm Sampling location Sample 1 xi ≥ 0,5 µm (counts per 28,3 l) Sample 2 xi ≥ 0,5 µm (counts per 28,3 l) Sample 3 xi ≥ 0,5 µm (counts per 28,3 l) Location sample average (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 5 limit for ≥ 0,5 µm particle size Pass/fail 1 836 3 520 Pass 3 520 Pass 3 201 3 520 Pass 4 165 3 520 Fail 0,5 3 520 Pass 3 520 Pass 3 520 Pass 1 041 3 520 Pass 3 424 3 520 Pass 1 918 3 520 Pass B.4.6 At sampling location 4, the average sample volume concentration of 4 165 does not meet ISO Class 5 maximum particle count criteria of 3 520. At location 3 and location 9, one of the individual particle count concentrations does not meet the limit established in Table 1; however, the average particle concentration for location 3 and the average particle concentration for location 9 do meet the limit established in Table 1. Because location 4 does not meet the air cleanliness by particle concentration, the cleanroom does not meet the required ISO Class. B.5 Example 5 B.5.1 A cleanroom has a floor area of 10,7 m2 and is specified to be ISO Class 7,5 in operation. The classification is to be performed using a discrete-particle counter having a flow rate of 28,3 litres per minute. Only one particle size (D ≥ 0,5 µm) is considered. The number of sampling locations is determined to be 6, based on Table A.1.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 24 ---  ISO 14644-1:2015(E) B.5.2 The particle concentration limit for ISO Class 7,5 at ≥ 0,5 µm is obtained from Table E.1. C D N D n N ≥ ( ) = ×      

= 0 5 0 1 7 5 0 5 2 08 , , , , , µ µ m where and m Cn ≥ ( ) = ×       0 5 0 1 0 5 7 5 2 08 , , , , , µm Cn ≥ ( ) = × 0 5 31622777 0 03516757 , , µm Cn ≥ ( ) =

0 5 1112096 1110000 , µm rounded to three significant digits particles/m3 B.5.3 The required single sample volume can be calculated from Formula (A.2) as follows: V n m s =       × 1000 C , Vs =       ×

1112000 1000 0 01799 , litres The single sample volume has been calculated to be 0,01799 l. As the discrete-particle counter being used for this test had a flow rate of 28,3 l per minute, a 1-min single sample count would be required (see A.4.4) and therefore 28,3 l would be sampled for each single sample volume. B.5.4 At each sampling location the number of single sample volumes varies from 1 to 3. The number of particles per cubic metre, xi, is calculated for each location and recorded in Table B.6. Table B.6 — Sampling data for particles ≥ 0,5 μm Sampling location Sample 1 xi ≥ 0,5 µm (counts per 28,3 l) Sample 2 xi ≥ 0,5 µm (counts per 28,3 l) Sample 3 xi ≥ 0,5 µm (counts per 28,3 l) Location sample average (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 7,5 limit for 0,5 µm particle size Pass/ fail 11 679 11 679 412 269 1 110 000 Pass 9 045 9 045 319 289 1 110 000 Pass 12 699 12 699 448 275 1 110 000 Pass 26 232 27 555 34 632 29 473 1 040 397 1 110 000 Pass 7 839 7 839 276 717 1 110 000 Pass 13 669 13 669 482 516 1 110 000 Pass B.5.5 At sampling location 4, the third sample volume concentration of 1 222 507 (34 632 × 35,3) did not meet the ISO Class 7,5 maximum particle count criteria of 1 110 000. The concentration of each single sample volume does not meet the limit established by using Table  E.1; however, the average particle concentration for each of the sampling locations does meet the limit established by application of Table E.1. Therefore, the air cleanliness by particle concentration of the cleanroom meets the required ISO Class.  18 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 25 ---  ISO 14644-1:2015(E) B.6 Example 6 B.6.1 A cleanroom has a floor area of 2 100 m2 and is specified to be ISO Class 7 in operation. The classification is to be performed using a discrete-particle counter having a flow rate of 28,3 litres per minute. Only one particle size (D ≥ 0,5 µm) is considered. The number of sampling locations, NL, given by Table A.1 is limited to cleanrooms of 1 000 m2 area. For a cleanroom of 2 100 m2, the number of sampling locations, NL, is derived from Formula (A.1): 2100 1000 56 7 ×      

, rounded to B.6.2 The particle concentration limit for ISO Class 7 at ≥ 0,5 µm is taken from Table 1: Cn (≥ 0,5 µm) = 352 000 particles/m3 B.6.3 The required single sample volume can be calculated from Formula (A.2) as follows: V n m s =       × 1000 C , Vs =       × 352000 1000 Vs = ( )× 0 0000568 1000 , Vs litres = 0 0568 ,

The single sample volume has been calculated to be 0,0568 l. As the discrete-particle counter being used for this test had a flow rate of 28,3 l per minute, a 1-min single sample count would be required (see A.4.4) and therefore 28,3 l would be sampled for each single sample volume. B.6.4 At each sampling location only one sample volume is taken. The number of particles per cubic metre, xi, is calculated for each location and recorded in Table B.7.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 26 ---  ISO 14644-1:2015(E) Table B.7 — Sampling data for particles ≥ 0,5 μm Sampling location Sample 1 xi ≥ 0,5 µm (counts per 28,3 l) Location sample average (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 7 limit for 0,5 µm particle size Pass/fail 5 678 5 678 200 434 352 000 Pass 7 654 7 654 270 187 352 000 Pass 2 398 2 398 84 650 352 000 Pass 4 578 4 578 161 604 352 000 Pass 8 765 8 765 309 405 352 000 Pass 4 877 4 877 172 159 352 000 Pass 8 723 8 723 307 922 352 000 Pass 7 632 7 632 269 410 352 000 Pass 7 643 7 643 269 798 352 000 Pass 6 756 6 756 238 487 352 000 Pass 5 678 5 678 200 434 352 000 Pass 5 476 5 476 193 303 352 000 Pass 8 576 8 576 302 733 352 000 Pass 7 765 7 765 274 105 352 000 Pass 3 456 3 456 121 997 352 000 Pass 5 888 5 888 207 847 352 000 Pass 3 459 3 459 122 103 352 000 Pass 7 666 7 666 270 610 352 000 Pass 8 567 8 567 302 416 352 000 Pass 8 345 8 345 294 579 352 000 Pass 7 998 7 998 282 330 352 000 Pass 7 665 7 665 270 575 352 000 Pass 7 789 7 789 274 952 352 000 Pass 8 446 8 446 298 144 352 000 Pass 8 335 8 335 294 226 352 000 Pass 7 988 7 988 281 977 352 000 Pass 7 823 7 823 276 152 352 000 Pass 7 911 7 911 279 259 352 000 Pass 7 683 7 683 271 210 352 000 Pass 7 935 7 935 280 106 352 000 Pass 6 534 6 534 230 651 352 000 Pass 4 667 4 667 164 746 352 000 Pass 6 565 6 565 231 745 352 000 Pass 8 771 8 771 309 617 352 000 Pass 5 076 5 076 179 183 352 000 Pass 6 678 6 678 235 734 352 000 Pass 7 100 7 100 250 630 352 000 Pass 8 603 8 603 303 686 352 000 Pass  20 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 27 ---  ISO 14644-1:2015(E) Sampling location Sample 1 xi ≥ 0,5 µm (counts per 28,3 l) Location sample average (counts per 28,3 l) Location concentration average (counts per m3 = location average × 35,3) ISO Class 7 limit for 0,5 µm particle size Pass/fail 7 609 7 609 268 598 352 000 Pass 7 956 7 956 280 847 352 000 Pass 7 477 7 477 263 939 352 000 Pass 7 145 7 145 252 219 352 000 Pass 6 998 6 998 247 030 352 000 Pass 7 653 7 653 270 151 352 000 Pass 6 538 6 538 230 792 352 000 Pass 3 679 3 679 129 869 352 000 Pass 4 887 4 887 172 512 352 000 Pass 7 648 7 648 269 975 352 000 Pass 8 748 8 748 308 805 352 000 Pass 7 689 7 689 271 422 352 000 Pass 7 345 7 345 259 279 352 000 Pass 7 888 7 888 278 447 352 000 Pass 7 765 7 765 274 105 352 000 Pass 6 997 6 997 246 995 352 000 Pass 6 913 6 913 244 029 352 000 Pass 7 474 7 474 263 833 352 000 Pass 8 776 8 776 309 793 352 000 Pass B.6.5 Each value of the concentration for D ≥ 0,5 µm is less than the limit of 352 000 particles/m3 established in Table 1; therefore, the air cleanliness by particle concentration of the cleanroom meets the required ISO Class.  Table B.7 (continued) © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 28 ---  ISO 14644-1:2015(E) Annex C (informative)

Counting and sizing of airborne macroparticles C.1 Principle In some situations, typically those related to specific process requirements, alternative levels of air cleanliness may be specified on the basis of particle populations that are not within the size range applicable to classification. The maximum permitted concentration of such particles and the choice of test method to verify compliance are matters for agreement between the customer and the supplier. Considerations for test methods and prescribed formats for specification are given in C.2. C.2 Consideration of particles larger than 5 µm (macroparticles) — M descriptor C.2.1 Application If contamination risks caused by particles larger than 5 µm are to be assessed, sampling devices and measurement procedures appropriate to the specific characteristics of such particles should be employed. The measurement of airborne particle concentrations with size distributions having a threshold size between 5 µm and 20 µm can be made in any of three defined occupancy states: as-built, at-rest and operational. As particle liberation within the process environment normally dominates the macroparticle fraction of the airborne particle population, the identification of an appropriate sampling device and measurement procedure should be addressed on an application-specific basis. Factors such as density, shape, volume and aerodynamic behaviour of the particles need to be taken into account. Also, it may be necessary to put special emphasis on specific components of the total airborne population, such as fibres. C.2.2 M descriptor format The M descriptor may be specified as a complement to the air cleanliness class by particle concentration. The M descriptor is expressed in the format “ISO M (a; b); c” where a is the maximum permitted concentration of macroparticles (expressed as macroparticles per cubic metre of air); b is the equivalent diameter (or diameters) associated with the specified method for measuring macroparticles (expressed in micrometres); c is the specified measurement method. EXAMPLE 1 To express an airborne concentration of 29 particles/m3 in the particle size range ≥ 5 µm based on the use of an LSAPC, the designation would be: “ISO M (29; ≥ 5 µm); LSAPC”. EXAMPLE 2 To express an airborne particle concentration of 2 500 particles/m3 in the particle size range of > 10 µm based on the use of a time-of-flight aerosol particle counter to determine the aerodynamic diameter of the particles, the designation would be: “ISO M (2 500; ≥ 10 µm); time-of-flight aerosol particle counter”.  22 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 29 ---  ISO 14644-1:2015(E) EXAMPLE 3 To express an airborne particle concentration of 1 000 particles/m3 in the particle size range of 10 to 20 µm, based on the use of a cascade impactor followed by microscopic sizing and counting, the designation would be: “ISO M (1 000; 10 to 20 µm); cascade impactor followed by microscopic sizing and counting”. NOTE 1 If the population of airborne particles being sampled contains fibres, they can be accounted for by supplementing the M descriptor with a separate descriptor for fibres, which has the format “Mfibre (a; b); c”. NOTE 2 Suitable methods of test for concentrations of airborne particles larger than 5  µm are given in IEST-G-CC1003.[2] C.3 Airborne particle count for macroparticles C.3.1 Principle This test method describes the measurement of airborne particles with a threshold size larger than 5 µm in diameter (macroparticles). The procedure given in C.3 has been adapted from IEST-G- CC1003:1999.[2] Measurements can be made in a cleanroom or clean zone installation in any of the three designated occupancy states: as-built, at-rest or operational. The measurements are made to define the concentration of macroparticles, and the principles in 5.1, 5.2 and 5.4 may be applied. The need for proper sample acquisition and handling to minimize losses of macroparticles in the sample handling operations is emphasized. C.3.2 General The number of sampling locations, location selection and quantity of data required should be in accordance with A.4. The customer and supplier should agree upon the maximum permitted concentration of macro-particles, the equivalent diameter of the particles and the specified measurement method. Other appropriate methods of equivalent accuracy and which provide equivalent data may be used by agreement between customer and supplier. If no other method has been agreed upon, or in case of dispute, the reference method in Annex C should be used. C.3.3 Sample handling considerations Careful sample collection and handling is required when working with macroparticles. A complete discussion of the requirements for systems, which can be used for isokinetic or anisokinetic sampling and particle transport to the point of measurement, is provided in IEST-G-CC1003:1999.[2] C.3.4 Measurement methods for macroparticles There are two general categories of macroparticle measurement methods. Comparable results may not be produced if different measurement methods are used. Correlation between different methods may not be possible for this reason. The methods and particle size information produced by the various methods is summarized in C.3.4.1 and C.3.4.2. C.3.4.1 In situ measurement Using in situ measurement of the concentration and size of macroparticles with a time-of-flight particle counter or an LSAPC: a) LSAPC measurement (C.4.1.2) will report macroparticles using particle size based upon an equivalent optical diameter; b) time-of-flight particle size measurement (C.4.1.3) will report macroparticles using particle size based upon an aerodynamic diameter.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 30 ---  ISO 14644-1:2015(E) C.3.4.2 Collection Collection by filtration or inertial effects, followed by microscopic measurement of the number and size of collected particles: a) filter collection and microscopic measurement (C.4.2.2) will report macroparticles using particle size based upon the agreed diameter; b) cascade impactor collection and microscopic measurement (C.4.2.3) will report macroparticles using particle size based upon the choice of reported particle diameter. C.4 Methods for macroparticle measurement C.4.1 Macroparticle measurement without particle collection C.4.1.1 General Macroparticles can be measured without collecting particles from the air. The process involves optical measurement of the particles suspended in the air. An air sample is moved at a specific flow rate through a LSAPC, which reports either the equivalent optical diameter or the aerodynamic diameter of the particles. C.4.1.2 Light-scattering particle counter (LSAPC) measurement Procedures for macroparticle measurement using an LSAPC are the same as those in Annex  A for airborne particle count with one exception. The exception is that the LSAPC in this case does not require sensitivity for detection of particles less than 1  µm since data are required only for macroparticle counting. Care is required to ensure that the LSAPC samples directly from the air at the sampling location. The LSAPC should have a sample flow rate of at least 28,3 l/min and should be fitted with an inlet probe sized for isokinetic sampling in unidirectional flow zones. In areas where non-unidirectional flow exists, the LSAPC should be located with the sample inlet facing vertically upward. A sampling probe should be selected to permit close to isokinetic sampling in areas with unidirectional flow. If this is not possible, set the sampling probe inlet facing into the predominant direction of the airflow; in locations where the airflow being sampled is not controlled or predictable (e.g. non- unidirectional airflow), the inlet of the sampling probe shall be directed vertically upward. The transit tube from the sampling probe inlet to the LSAPC sensor should be as short as possible. For sampling of particles larger than and equal to 1 µm, the transit tube length should not exceed the manufacturer’s recommended length and diameter, and will typically be no longer than 1 m in length. Sampling errors due to large particle loss in sampling systems should be minimised. The LSAPC size range settings are established so that only macroparticles are detected. The data from one size below 5 µm should be recorded to ensure that the concentration of detected particles below the macroparticle size is not sufficiently high to cause coincidence error in the LSAPC measurement. The particle concentration in that lower size range, when added to the macroparticle concentration, should not exceed 50 % of the maximum recommended particle concentration specified for the LSAPC being used. C.4.1.3 Time-of-flight particle size measurement Macroparticle dimensions can be measured with time-of-flight apparatus. An air sample is drawn into the apparatus and accelerated by expansion through a nozzle into a partial vacuum, where the measurement region is located. Any particle in that air sample will accelerate to match the air velocity in the measurement region. The particles’ acceleration rate will vary inversely with mass of particle. The relationship between the air velocity and the particle velocity at the point of measurement can be used to determine the aerodynamic diameter of the particle. With knowledge of the pressure difference between the ambient air and the pressure at the measurement region, the air velocity can be calculated directly. The particle velocity is measured by the time of flight between two laser beams. The time-of-  24 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 31 ---  ISO 14644-1:2015(E) flight apparatus should measure aerodynamic diameters of particles up to 20 µm. Sample acquisition procedures are the same as those required when using a LSAPC to measure macroparticles. In addition, the same procedures as for the LSAPC are used with this apparatus in order to establish the particle size ranges to be reported. C.4.2 Macroparticle measurement with particle collection C.4.2.1 General Macroparticles can be measured by collecting particles from the air. An air sample is transported at a specific flow rate through a collection device. Microscopic analysis is used to count the collected particles. NOTE The mass of the collected particles can also be determined but since the air cleanliness is determined by number concentration this is not addressed in this part of ISO 14644. C.4.2.2 Filter collection and microscopic measurement Select a membrane filter and a holder or a pre-assembled aerosol monitor; a membrane with pore size of 2 µm or fewer should be used. Label the filter holder to identify the filter holder location and installation. Connect the outlet to a vacuum source that will draw air at the required flow rate. If the sampling location in which macroparticle concentration is to be determined is a unidirectional flow area, the flow rate should be established to permit isokinetic sampling into the filter holder or aerosol monitor inlet and the inlet should face into the unidirectional flow. Determine the sample volume required by using Formula (C.1). Remove the cover from the membrane filter holder or aerosol monitor and store in a clean location. Sample the air at the sampling locations as determined by agreement between the customer and supplier. If a portable vacuum pump is used to draw air through the membrane filter, the exhaust from that pump should be vented outside the clean installation or through a suitable filter. After the sample collection has been completed, replace the cover on the filter holder or aerosol monitor. The sample holder should be transported in such a manner that the filter membrane is maintained in a horizontal position at all times and is not subjected to vibration or shock between the time the sample is captured and when it is analysed. Count the particles on the filter surface (see ASTM F312-08).[3] C.4.2.3 Cascade impactor collection and measurement In a cascade impactor particle separation is carried out by inertial impaction of particles. The sampled airflow passes through a series of jets of decreasing orifice size. The larger particles are deposited directly below the largest orifices and smaller particles are deposited at each successive stage of the impactor. The aerodynamic diameter correlates directly with the regional collection of particles in the impactor flow path. For the measurement of the air cleanliness by particle concentration a type of cascade impactor meant for collection and counting of macroparticles can be used. In this one the particles are deposited upon the surfaces of removable plates that are removed for subsequent microscopic examination. Sampling flow rates of 0, 47 litres/sec or more are typically used for this type of cascade impactor. C.5 Procedure for macroparticle count Determine the “ISO M (a; b); c” descriptor concentration in the selected particle size range(s), as agreed between customer and supplier, and report the data. At each sampling location, sample a volume of air sufficient to detect a minimum of 20 particles for the selected particle size at the determined concentration limit.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 32 ---  ISO 14644-1:2015(E) The single sample volume, Vs, per sampling location is determined by using Formula (C.1): Vs n m

      × 1000 C ,

(C.1) where Vs is the minimum single sample volume per location, expressed in litres (except see D.4.2); Cn,m is the class limit (number of particles per cubic metre) for the largest considered particle size specified for the relevant class; is the number of particles that could be counted if the particle concentration were at the class limit. Where information on the stability of macroparticle concentration is required, make three or more measurements at selected locations at time intervals agreed between customer and supplier. Set up the sample inlet probe of the selected apparatus and undertake the test. C.6 Test reports for macroparticle sampling The following test information and data should be recorded: a) definition of the particle sizes to which the apparatus responds; b) measurement method; c) method of measurement of M descriptor level or limit as an adjunct to the ISO Class; d) type designations of each measurement instrument and apparatus used and its calibration status; e) ISO Class of the installation; f) macroparticle size range(s) and the counts for each size range reported; g) apparatus inlet sample flow rate and flow rate through sensing volume; h) sampling location(s); i) sampling schedule plan for classification or sampling protocol plan for testing; j) occupancy state(s); k) other relevant data for measurement such as stability of macroparticle concentration. C.7 Adaptation of the macroparticle descriptor to accommodate consideration of ≥ 5 µm particle size for ISO Class 5 cleanrooms In order to express an airborne concentration of 29 particles/m3 in the particle size range ≥ 5 µm based on the use of an LSAPC, the designation would be “ISO M (29; ≥ 5 µm); LSAPC” and for 20 particle/m3 the designation would be “ISO M (20; ≥ 5 µm); LSAPC” (see Table 1, Note f).  26 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 33 ---  ISO 14644-1:2015(E) Annex D (informative)

Sequential sampling procedure D.1 Background and limitations D.1.1 Background In some circumstances where it is necessary or required to classify a clean controlled environment with a very low particle concentration at the class limit, sequential sampling is a useful technique that allows reduction of the sample volume and sampling time. The sequential sampling technique measures the rate of counting and predicts the likelihood of passing or failing to meet the requirements of the ISO Class. If the air being sampled is significantly more or significantly less contaminated than the specified class concentration limit for the considered particle size, use of the sequential sampling procedure can reduce sample volumes and sampling times, often dramatically. Some savings may also to be realized when the concentration is near the specified limit. Sequential sampling is most appropriate for air cleanliness of ISO Class 4 or cleaner. It may also be used for other classes when the limit for the chosen particle size is low. In that case, the required sample volume may be too high for detecting 20 expected counts. NOTE For further information on sequential sampling, see IEST-G-CC1004[4] or JIS B 9920:2002.[5] D.1.2 Limitations The principal limitations of sequential sampling are a) the procedure is only applicable when expected counts from a single sample are < 20 for the largest particle size (see A.4.4), b) each sample measurement requires supplementary monitoring and data analysis, which can be facilitated through computerised automation, and c) particle concentrations are not determined as precisely as with conventional sampling procedures due to the reduced sample volume. D.2 Basis for the procedure The procedure is based on comparison of real-time cumulative particle counts to reference count values. Reference values are derived from formulae for upper- and lower-limit boundaries: upper limit: Cfail = 3,96 + 1,03 E (D.1) lower limit: Cpass = −3,96 + 1,03 E (D.2) where Cfail is the upper limit for the observed count; Cpass is the lower limit for the observed count; E is the expected count (shown by Formula (D.5), the class limit).  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 34 ---  ISO 14644-1:2015(E) According to Formula (A.2), the single sample volume, Vs, is calculated as follows: V n m s =       × 1000 C ,

(D.3) where Vs is the minimum single sample volume per location, expressed in litres; Cn,m is the class limit (number of particles per cubic metre) for the considered particle size speci- fied for the relevant class; is the defined number of particles that could be counted if the particle concentration were at the class limit. The total sampling time tt is calculated as follows: t V Q t = s (D.4) where Vs is the accumulative sample volume (litres); Q is the sampling flow rate of the particle counter (litres/s). The expected count is defined as follows: E Q t Cn m

× × , 1000

(D.5) where t is sampling time (in seconds). To aid in understanding, a graphical illustration of the sequential sampling procedure is provided in Figure D.1. As air is being sampled at each designated sampling location, the running total particle count is continuously compared to the expected count for the proportion of the prescribed total volume that has been sampled. If the running total count is less than the lower limit Cpass corresponding to the expected count, the air being sampled is found to meet the specified class or concentration limit, and sampling is halted. If the running count exceeds the upper limit Cfail corresponding to the expected count, the air being sampled fails to meet the specified class or concentration limit, and sampling is halted. As long as the running count remains between the upper and lower limits, sampling continues until the observed count becomes 20 or the cumulative sample volume, V, becomes equal to the minimum single sample volume, Vs, where the expected count becomes 20. In Figure D.1, the number of observed counts, C, is plotted versus the expected count, E, until either the sampling is halted or the count reaches 20. D.3 Procedure for sampling Figure  D.1 illustrates the boundaries established in Formulae  (D.1) and (D.2), as truncated by the limitations of E = 20, representing the time required to collect a full sample, and C = 20, the maximum observed count allowed.  28 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 35 ---  ISO 14644-1:2015(E) Key x expected count, E y observed count, C stop counting, FAIL (C ≥ 3,96 + 1,03E) continuous counting stop counting, PASS (C ≤ −3,96 + 1,03E) Figure D.1 — Boundaries for pass or fail by the sequential sampling procedure The observed count is plotted versus the expected count for air having a particle concentration precisely at the specified class level. The passage of time corresponds to increasing numbers of expected counts, with E = 20 representing the time required to accumulate a full sample volume if the particle concentration were at the class limit. The procedure for sequential sampling using Figure D.1 is as follows:

  1. record the total number of particles counted as a function of time;
  2. calculate the expected count following the procedure described in D.2, Formula (D.5);
  3. plot the total count versus the expected count as in Figure D.1;
  4. compare the count with the upper and lower limit lines of Figure D.1;
  5. if the cumulative observed count crosses the upper line, sampling at the location is stopped and the air is reported to have failed compliance with the specified class limit;
  6. if the cumulative observed count crosses the lower line, sampling is stopped and the air passes compliance with the specified class limit;
  7. if the cumulative observed count remains between the upper and lower lines, sampling will continue. If the total count is 20 or fewer at the end of the prescribed sampling period and has not crossed the upper line, the air is judged to have complied with the class limit. D.4 Examples of sequential sampling D.4.1 Example 1 a) Evaluation of a cleanroom with a target air cleanliness of ISO Class 3 (0,1 μm, 1 000 particles/m3) by the sequential sampling procedure. This procedure looks at the rate of count and seeks to predict likely pass or fail.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 36 ---  ISO 14644-1:2015(E) NOTE The sampling flow rate of particle counter is 0,0283 m3/min (28,3 l/min or 0,47 l/s). b) Preparation before measurement — method for calculation of limit values. Table D.1 shows the calculation result. First, the expected count is calculated based on sampling time. Next, the upper reference count and the lower reference count are calculated by using Formulae (D.1) and (D.2), or Figure D.1. Table D.1 — Calculation tabulation of the upper and lower reference count Measurement period Sampling time (s) Total sampled air volume Expected count Upper limit for the observed count Lower limit for the observed count t litre According to Formula (D.5) Cfail = 3,96 + 1,03 E Cpass = −3,96 + 1,03 E 1st 2,4 2,4 7 (6,4) N.A. (−1,5) 2nd 4,7 4,7 9 (8,8) 0 (0,9) 3rd 7,1 7,1 12 (11,2) 3 (3,3) 4th 9,4 9,4 14 (13,7) 5 (5,8) 5th 11,8 11,8 17 (16,1) 8 (8,2) 6th 14,2 14,1 19 (18,5) 10 (10,6) 7th 16,5 16,5 20 (21,0) 13 (13,0) 8th 18,9 18,9 20 (23,4) 15 (15,5) 9th 21,2 21,2 NOTE The numeric value in parentheses shows the result of calculation of the upper and lower limits for the observed count to one decimal place. However, as the actual data are integer values, each calculated value is handled at the time of evaluation as the integer value shown. The upper limit for the observed count is rounded up to the first decimal place of calculated value. The lower limit for the observed count is rounded down to the first decimal place of calculated value. When Cpass calculated according to Formula (D.2) is negative, it is denoted by ‘N.A.’ (not applicable). In this case, we cannot conclude that the air cleanliness satisfies the target ISO Class, even if the observed count is zero. c) Evaluation using sequential sampling procedure. The expected count provided in the first measurement is 2,4; it is judged to “FAIL” when the observed count is greater or equal to 7. However, when the observed count during this sampling period is between 0 and 6, the result cannot be judged. In this case, sampling is continued. When sampling is continued, the cumulative observed count may increase. Sampling is continued until either the prescribed single sample volume is achieved or the observed count has crossed one of the lines for Cpass or Cfail, respectively. If the cumulative observed count is 20 or fewer at the end of the prescribed sampling period and has not crossed the upper line, the air cleanliness classification is judged to “PASS”. If the cumulative observed count is less than or equal to the rounded down values for Cpass before achieving the full sampling period, the sampling is stopped and the classification is judged to “PASS”. D.4.2 Example 2 Evaluation of a cleanroom with a target air cleanliness of ISO Class 3 (0,5  µm, 35 particles/m3) by the sequential sampling procedure. The sampling flow rate of the particle counter (Q) is 0,0283 m3/min = 0,47 l/s.  30 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 37 ---  ISO 14644-1:2015(E) Calculate the single sample volume, VS, according to Formula (D.3). V n m s =       ×

×

1000 1000 571 429 C , , litres (D.6) Calculate the total sampling time, tt, according to Formula (D.4). This is the longest time necessary to evaluate the sampling location. The sequential sampling procedure should shorten this time. t V Q t =

= s 1211 5 20 19 , , s min (D.7) Calculate the result table:

  1. calculate the expected count, E, according to Formula (D.5); E Q t Cn m

    × × , 1000

(D.8) 2) calculate the upper and lower limit for the observed count according to Formulae (D.1) and (D.2); 3) the calculation result is shown in Table D.2 and Figure D.2. Table D.2 — Calculation result of the total sample air volume, expected count, upper limit and lower limit t (min) t (s) Total sampled air volume, Q × t Expected count, E Limits Upper, Cfail Lower, Cpass 28,3 1,0 5 (5,0) N.A. (−2,9) 56,6 2,0 7 (6,0) N.A. (−1,9) 84,9 3,0 8 (7,0) N.A. (−0,9) 113,2 4,0 9 (8,0) 0 (0,1) 141,5 5,0 10 (9,1) 1 (1,1) 169,8 5,9 11 (10,1) 2 (2,2) 198,1 6,9 12 (11,1) 3 (3,2) 226,4 7,9 13 (12,1) 4 (4,2) 254,7 8,9 14 (13,1) 5 (5,2) 283,0 9,9 15 (14,2) 6 (6,2) 311,3 10,9 16 (15,2) 7 (7,3) 339,6 11,9 17 (16,2) 8 (8,3) 367,9 12,9 18 (17,2) 9 (9,3) 396,2 13,9 19 (18,2) 10 (10,3) 424,5 14,9 20 (19,3) 11 (11,3) 452,8 15,8 20 (20,3) 12 (12,4) 1 020 481,1 16,8 20 (21,3) 13 (13,4) 1 080 509,4 17,8 20 (22,3) 14 (14,4) 1 140 537,7 18,8 20 (23,3) 15 (15,4) 1 200 566,0 19,8 20 (24,4) 16 (16,4) 20,19 = tt 1 211,5 571,429 = Vs In Figure D.2, the upper and lower limits for the observed count are plotted versus the count acquisition time. Each vertical bar shows the limits (upper and lower) at 1-min intervals.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 38 ---  ISO 14644-1:2015(E) Key x count time (min) y count limits (particles) upper limit for the observed count lower limit for the observed count Figure D.2 — Graphical representation of the pass or fail boundaries for sequential sampling Compare the cumulative observed count and the upper and lower limits and apply the procedure described in D.3. a) Fail situation, see Table D.3. Table D.3 — Example sequential sampling particle counts t (min) t (s) Expected count, E Limit for the cumulative ob- served count Observed count during interval Cumulative observed count, C Result Upper, Cfail Lower, Cpass 1,0 N.A. Continue 2,0 N.A. Continue 3,0 N.A. Continue 4,0 Continue 5,0 FAIL The expected count provided in the first measurement is 1,0; the cumulative observed count is judged to “FAIL” when it is greater than or equal to 5. However, when the cumulative observed count is between 0 and 5, it cannot be judged. In the present example, the sampling has to be continued. When the sampling is continued, the cumulative observed count increases. However, it is easy to judge because both the expected count and the reference count increase. In the 5th measurement (t = 300 s), the cumulative observed count is 11 and exceeds the upper limit (10). Then it is judged to “FAIL.”  32 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 39 ---  ISO 14644-1:2015(E) b) Pass situation see Table D.4. Table D.4 — Example sequential sampling particle counts t (min) t (s) Expected count, E Limits for the cumulative observed count Observed count during interval Cumulative observed count, C Result Upper, Cfail Lower, Cpass 1.0 N.A. Continue 2.0 N.A. Continue 3.0 N.A. Continue 4.0 PASS The expected count provided in the first measurement is 1,0, the cumulative observed count is judged to “FAIL” when it is greater than or equal to 5. However, when the observed count is between 0 and 5, it cannot be judged. In the present example, the sampling is continued, but the cumulative observed count does not increase. In the 4th measurement (t = 240 s), the cumulative observed count is 0 and is equal to the lower limit (0). Then it is judged to “PASS.”  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 40 ---  ISO 14644-1:2015(E) Annex E (informative)

Specification of intermediate decimal cleanliness classes and particle size thresholds E.1 Intermediate decimal cleanliness classes If intermediate decimal cleanliness classes are required, Table E.1 should be used. Table E.1 provides the permitted intermediate decimal air cleanliness classes. Uncertainties associated with particle measurement make increments of less than 0,5 inappropriate, and the notes beneath the table identify restrictions due to sampling and particle collection limitations. Table E.1 — Intermediate decimal air cleanliness classes by particle concentration Concentration of particles (particles/m3)a ISO Class number (N) 0,1 0,2 0,3 0,5 1,0 5,0 ISO Class 1,5 [32]b d d d d e ISO Class 2,5 [75]b [32]b d d e ISO Class 3,5 3 160 d e ISO Class 4,5 31 600 7 480 3 220 1 110 e ISO Class 5,5 316 000 74 800 32 200 11 100 2 630 e ISO Class 6,5 3 160 000 748 000 322 000 111 000 26 300 ISO Class 7,5 c c c 1 110 000 263 000 9 250 ISO Class 8,5f c c c 11 100 000 2 630 000 92 500 a All concentrations in the table are cumulative, e.g. for ISO Class 5,5, the 11 100 particles shown at 0,5 µm include all particles equal to and greater than this size. b These concentrations will lead to large air sample volumes for classification. See Annex  D, Sequential sampling procedure. c Concentration limits are not applicable in this region of the table due to very high particle concentration. d Sampling and statistical limitations for particles in low concentrations make classification inappropriate. e Sample collection limitations for both particles in low concentrations and sizes greater than 1 µm make classification inappropriate, due to potential particle losses in the sampling system. f This class is only applicable for the in-operation state.  34 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 41 ---  ISO 14644-1:2015(E) E.2 Intermediate particle sizes If intermediate particle sizes are required for any integer or decimal class, Formula (E.1) may be used to determine the maximum particle concentration at the considered particle size: C D n N

×       2 08 K ,

(E.1) where Cn is the maximum permitted concentration (particles per cubic metre) of airborne particles that are equal to and greater than the considered particle size. Cn is rounded to the nearest whole number, using no more than three significant figures; N is the ISO Class number, which shall not exceed a value of 9 or be less than 1; D is the considered particle size, in micrometres, that is not listed in Table 1; K is a constant, 0,1, expressed in micrometres.  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 42 ---  ISO 14644-1:2015(E) Annex F (informative)

Test instruments F.1 Introduction This annex describes the measuring apparatus that should be used for the recommended tests given in Annexes A, C and D. In this annex, data given in Tables F.1 and F.2 indicate the minimum necessary requirements for each item of apparatus. Measuring apparatus should be chosen subject to agreement between the customer and supplier. This annex is informative, and should not prevent the use of improved apparatus as it becomes available. Alternative test apparatus may be appropriate and may be used subject to agreement between customer and supplier. F.2 Instrument specifications The following instruments should be used for the recommended tests given in Annexes A, C and D: a) light scattering (discrete) airborne particle counter (LSAPC); NOTE The specifications for the LSAPC are given in ISO 21501-4:2007.[1] b) discrete-macroparticle counter; c) time-of-flight particle sizing apparatus; d) microscopic measurement of particles collected on filter paper. See ASTM F312-8.[3] The terms and definitions for these instruments are given in Clause 3. Table F.1 — Specifications for discrete-macroparticle counter Item Specification Measuring limits The minimum detectable size should be in the range 5 to 80 µm and be appropriate for the particle size under consideration and the instrument capability. The maximum particle number concentration of the LSAPC should be equal to or higher than maximum expected concentration for the particles under consideration Resolution 20 % for calibration particles of a size specified by the manufacturer Maximum permissible error 20 % for particle count at a specified size setting Table F.2 — Specifications for time-of-flight particle sizing apparatus Item Specification Measuring limits Particle size 0,5 to 20 µm; Particle concentration 1,0 × 103/m3 to 1,0 × 108/m3 Resolution aerodynamic diameter: 0,02 µm at 1,0 µm; 0,03 µm at 10 µm Maximum permissible error 10 % of full reading  36 © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 43 ---  ISO 14644-1:2015(E) Bibliography [1] ISO 21501-4:2007, Determination of particle size distribution — Single particle light interaction methods — Part 4: Light scattering airborne particle counter for clean spaces [2] ASTM  F312-08, Standard Test Methods for Microscopical Sizing and Counting Particles from Aerospace Fluids on Membrane Filters. ASTM International [3] IEST-G-CC1003. Measurement of Airborne Macroparticles. Institute of Environmental Sciences and Technology, Arlington Heights, Illinois, 1999 [4] IEST-G-CC1004. Sequential-Sampling Plan for Use in Classification of the Particulate Cleanliness of Air in Cleanrooms and Clean Zones. Institute of Environmental Sciences and Technology, Arlington Heights, Illinois, 1999 [5] JIS B 9920:2002, Classification of air cleanliness for cleanrooms. Japanese Standards Association  © ISO 2015 – All rights reserved Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

--- PAGE 44 ---  ISO 14644-1:2015(E)  © ISO 2015 – All rights reserved ICS 13.040.35 Price based on 37 pages Este documento ha sido adquirido por CVTEC el 3 de Febrero de 2016. Para poder utilizarlo en un sistema de red interno, deberá disponer de la correspondiente licencia de AENOR

Source: ISO 14644-5.pdf Pages: 52

--- PAGE 1 ---

Reference number ISO 14644-5:2004(E) © ISO 2004

INTERNATIONAL STANDARD ISO 14644-5 First edition 2004-08-15 Cleanrooms and associated controlled environments — Part 5: Operations Salles propres et environnements maîtrisés apparentés — Partie 5: Exploitation

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--- PAGE 2 --- ISO 14644-5:2004(E) PDF disclaimer This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat accepts no liability in this area. Adobe is a trademark of Adobe Systems Incorporated. Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.

© ISO 2004 All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISO's member body in the country of the requester. ISO copyright office Case postale 56 • CH-1211 Geneva 20 Tel. + 41 22 749 01 11 Fax + 41 22 749 09 47 E-mail copyright@iso.org Web www.iso.org Published in Switzerland

ii © ISO 2004 – All rights reserved

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--- PAGE 3 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved iii

Contents Page Foreword............................................................................................................................................................ iv Introduction ........................................................................................................................................................ v Scope...................................................................................................................................................... 1 Normative references ........................................................................................................................... 1 Terms and definitions........................................................................................................................... 2 Specification of requirements ............................................................................................................. 3 Annex A (informative) Operational systems.................................................................................................... 7 Annex B (informative) Cleanroom clothing.................................................................................................... 13 Annex C (informative) Personnel .................................................................................................................... 18 Annex D (informative) Stationary equipment................................................................................................. 22 Annex E (informative) Materials and portable equipment............................................................................ 26 Annex F (informative) Cleanroom cleaning ................................................................................................... 33 Bibliography ..................................................................................................................................................... 43

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--- PAGE 4 --- ISO 14644-5:2004(E) iv © ISO 2004 – All rights reserved

Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2. The main task of technical committees is to prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 14644-5 was prepared by Technical Committee ISO/TC 209, Cleanrooms and associated controlled environments. ISO 14644 consists of the following parts, under the general title Cleanrooms and associated controlled environments:  Part 1: Classification of air cleanliness  Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1  Part 3: Test methods  Part 4: Design, construction and start-up  Part 5: Operations  Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments)  Part 8: Classification of airborne molecular contamination The following part is under preparation:  Part 6: Terms and definitions

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--- PAGE 5 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved v

Introduction Industries and organizations of all kinds utilize cleanrooms. Operational procedures have a profound effect on the cleanliness levels achieved during the operation of the cleanroom and equipment. Consistent quality is cleanliness dependent. Operational cleanliness can only be attained and maintained through a deliberate programme established to specify, measure and enforce defined operational procedures. Regulatory agencies that have authority over processes and products produced in the cleanroom may require additional procedures and measures of cleanliness not covered in this general operating standard. This part of ISO 14644 addresses normative and informative operational requirements related to: a) providing a system that defines policies and operational procedures; b) clothing used to isolate human-generated contamination from the cleanroom environment; c) training of personnel inside the cleanroom and monitoring their compliance to specified procedures and disciplines; d) transfer, installation and maintenance of stationary equipment (selection criteria is not discussed); e) selection and use of materials and portable equipment in the cleanroom; f) maintaining the cleanliness of the cleanroom through systematic cleaning and monitoring procedures.

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--- PAGE 7 --- INTERNATIONAL STANDARD ISO 14644-5:2004(E)

© ISO 2004 – All rights reserved

Cleanrooms and associated controlled environments — Part 5: Operations Scope This part of ISO 14644 specifies basic requirements for cleanroom operations. It is intended for those planning to use and operate a cleanroom. Aspects of safety that have no direct bearing on contamination control are not considered in this part of ISO 14644 and national and local safety regulations must be observed. This document considers all classes of cleanrooms used to produce all types of products. Therefore, it is broad in application and does not address specific requirements for individual industries. Methods and programmes for routine monitoring within cleanrooms are not covered in detail in this part of ISO 14644 but reference is made to ISO 14644-2 and ISO 14644-3 for monitoring particles and ISO 14698-1 and ISO 14698-2 for monitoring micro-organisms. Normative references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 14644-1:1999, Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness ISO 14644-2:2000, Cleanrooms and associated controlled environments — Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1 ISO 14644-3:—1), Cleanrooms and associated controlled environments — Part 3: Test methods ISO 14644-4:2001, Cleanrooms and associated controlled environments — Part 4: Design, construction and start-up ISO 14698-1:2003, Cleanrooms and associated controlled environments — Biocontamination control — Part 1: General principles and methods ISO 14698-2:2003, Cleanrooms and associated controlled environments — Biocontamination control — Part 2: Evaluation and interpretation of biocontamination data

  1. To be published. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 8 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

Terms and definitions For the purposes of this part of ISO 14644, the following terms and definitions apply.

3.1 General Terms

3.1.1 biocleanroom cleanroom used for products and processes that are sensitive to microbiological contamination 3.1.2 changing room room where people entering or leaving a cleanroom put on or take off cleanroom clothing NOTE Adapted from ISO 14644-4:2001, 3.1. 3.1.3 cross-over bench bench that is used as an aid to changing of cleanroom clothing and which provides a barrier to the tracking of floor contamination 3.1.4 disinfection removal, destruction or de-activation of micro-organisms on objects or surfaces 3.1.5 fibre particle having an aspect (length-to-width) ratio of 10 or more [ISO 14644-1:1999, 2.2.7] 3.1.6 operator person working in the cleanroom performing production work or carrying out process procedures 3.1.7 particle minute piece of matter with defined physical boundaries NOTE For classification purposes refer to ISO 14644-1:1999. 3.1.8 personnel persons entering the cleanroom for any purpose 3.1.9 separative device equipment utilizing constructional and dynamic means to create assured levels of separation between the inside and the outside of a defined volume EXAMPLES Some industry-specific examples of separative devices are clean air hoods, containment enclosures, gloveboxes, isolators and minienvironments. 3.1.10 unidirectional airflow controlled airflow through the entire cross-section of a clean zone with a steady velocity and approximately parallel airstreams NOTE This type of airflow results in a directed transport of particles from the clean zone. [ISO 14644-4:2001, 3.11] Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 9 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

3.2 Occupancy states

3.2.1 as-built condition where the installation is complete with all services connected and functioning but with no production equipment, materials or personnel present [ISO 14644-4:2001, 2.4.1] 3.2.2 at-rest condition where the installation is complete with equipment installed and operating in a manner agreed upon by the customer and supplier, but with no personnel present [ISO 14644-4:2001, 2.4.2] 3.2.3 operational condition where the installation is functioning in the specified manner, with the specified number of personnel present and working in the manner agreed upon [ISO 14644-4:2001, 2.4.3] Specification of requirements

4.1 Operational systems

4.1.1 A system of operational procedures shall be established and documented that will provide a

framework for producing the quality products and processes for which the cleanroom was designed. 4.1.2 A set of risk factors, appropriate for the use of the cleanroom, shall identify the areas where there is a risk of contamination to the process. A method for monitoring these risks shall be instituted so that action can be taken when conditions violate the contamination limits for the cleanroom classification. NOTE Although not covered in detail in this part of ISO 14644, it is important to routinely monitor the operation of a cleanroom. Guidance for monitoring particles is given in ISO 14644-2 and ISO 14644-3. Guidance for monitoring biocontamination is given in ISO 14698-1 and ISO 14698-2. 4.1.3 A system for training personnel in cleanroom procedures shall be instituted. A method for monitoring compliance to those training procedures shall be specified.

4.1.4 A documentation system shall be maintained to provide evidence that all personnel have received

suitable levels of training for their assignments.

4.1.5 A set of procedures shall be documented to describe how the cleanroom mechanical systems are to

be operated, maintained, repaired and monitored (see ISO 14644-4).

4.1.6 All activities that modify, supplement or enlarge the cleanroom shall be planned and include all

relevant personnel. Any significant change of operational use may be subject to re-qualification of the installation in compliance with ISO 14644-2.

4.1.7 A system shall be documented that encourages and enforces safety for personnel in the cleanroom

that may influence aspects of contamination control. NOTE Informative guidance concerning the operational systems requirements listed in 4.1.1 to 4.1.7 can be found in Annex A. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 10 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

4.2 Cleanroom clothing

4.2.1 Cleanroom clothing shall protect the environment and products from contamination generated by the

personnel and their everyday clothing. To maximize this containment, the choice of barrier fabric, the clothing style and extent of coverage of personnel by the cleanroom clothing shall be established. 4.2.2 Cleanroom clothing shall be made of fabrics and materials that will resist breakdown (minimal linting) and therefore not shed contamination.

4.2.3 The frequency of changing into fresh cleanroom clothing before entering the cleanroom shall be

determined in accordance with the product and process cleanliness requirements. 4.2.4 Reusable cleanroom clothing shall be processed at regular intervals to remove contamination.

4.2.5 The necessary cleaning, processing (including sterilization or disinfection where required) and

packaging of clothing shall be defined. 4.2.6 Cleanroom clothing shall be transported and stored in a specified manner to minimize contamination. 4.2.7 Cleanroom clothing (clean packaged or dirty) shall not be removed beyond the confines of the storage area and cleanroom except for laundering, repair or exchange purposes.

4.2.8 Cleanroom clothing shall be put on and taken off in such a way that the spread of contamination is

avoided or minimized. 4.2.9 If clothing is to be reused, it shall be removed and stored to ensure that contamination is minimized.

4.2.10 Cleanroom clothing shall be checked at regular intervals to ensure that it retains acceptable

contamination control characteristics. 4.2.11 Consideration shall be given for the comfort of personnel wearing the cleanroom clothing. 4.2.12 Consideration shall be given to special (e.g. chemical, physical or microbiological) properties of the clothing that may be necessary for specific applications.

4.2.13 Consideration shall be given to special concerns for cleanroom clothing during and after emergency

evacuations. NOTE Informative guidance concerning cleanroom clothing requirements listed in 4.2.1 to 4.2.13 can be found in Annex B.

4.3 Personnel

4.3.1 Personal and other items not intended for cleanroom use shall not be allowed inside the cleanroom,

unless approved. 4.3.2 Personnel shall be instructed in hygiene-related issues that will prepare them for properly working in the cleanroom environment. 4.3.3 A policy concerning jewellery, cosmetics and similar materials that can cause contamination problems shall be determined.

4.3.4 Cleanroom personnel shall be trained to conduct themselves in a manner that minimizes generation

of contamination which can be transferred or deposited on or into the product.

4.3.5 Personnel shall be protected against hazards. Personnel shall receive safety training for all known

health and safety risks associated with their work. NOTE Informative guidance concerning personnel requirements listed in 4.3.1 to 4.3.5 can be found in Annex C. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 11 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

4.4 Stationary equipment

4.4.1 All equipment, with its associated moving and rigging equipment, shall be thoroughly cleaned or

decontaminated, or both, before being transported into the cleanroom environment.

4.4.2 Procedures relating to the entry of equipment into a controlled environment shall be specified to

ensure that all equipment undergoes the necessary cleaning and decontaminating.

4.4.3 Installation of equipment shall be planned and carried out to minimize the impact on the cleanroom

environment.

4.4.4 Equipment maintenance, repairs and calibration procedures shall be performed in such a way as to

control and minimize contamination of the cleanroom.

4.4.5 Documented procedures relating to maintenance work and repairs shall be specified to control

contamination.

4.4.6 Preventive maintenance schedules shall be established and timed to renew and replace components

before the components become contamination sources. NOTE Informative guidance concerning stationary equipment requirements listed in 4.4.1 to 4.4.6 can be found in Annex D.

4.5 Materials and portable and mobile equipment

4.5.1 All materials, as well as portable and mobile equipment, shall be appropriate for the level of

cleanroom cleanliness, and in use, shall not compromise the product and process.

4.5.2 Procedures shall be established to ensure materials and portable and mobile equipment entering the

cleanroom are not contaminated. 4.5.3 Procedures shall be established to minimize the quantities of materials stored in the cleanroom. Consideration shall be given to shelf-life limitations, if applicable. 4.5.4 Materials stored in the cleanroom shall be subject to defined procedures and, where necessary, shall be held in protective storage or isolation. The risk of contamination arising from the storage and subsequent use of materials and portable and mobile equipment in the cleanroom shall be considered.

4.5.5 All used and waste materials shall be collected, identified and removed in accordance with defined

procedures. Waste materials shall be removed frequently and in a manner that does not compromise the cleanliness of the product or process. Procedures for hazardous materials must conform to statutory requirements set by local and other regulatory agencies. NOTE Informative guidance concerning materials and portable equipment requirements listed in 4.5.1 to 4.5.5 can be found in Annex E.

4.6 Cleanroom cleaning

4.6.1 Cleaning methods and procedures shall be specified and routinely followed to maintain cleanroom

surfaces at acceptable cleanliness levels. 4.6.2 Personnel responsible for the cleaning operation shall be designated and receive specific training for accomplishing the task. 4.6.3 Cleaning schedules shall be defined and carried out at effective frequencies to ensure that specified cleanliness levels are maintained.

4.6.4 Appropriate contamination checks shall be carried out on a routine basis to ensure the cleanroom is

maintained at specified levels. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 12 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

4.6.5 An assessment shall be made to identify any cleaning procedures that will place products or

processes at risk during the performance of such cleaning tasks. Preparations should be made to remove or cover work-in-process before cleaning begins.

4.6.6 Special cleaning procedures and techniques shall be defined for unavoidable accidents or system

failures that create contamination that places the cleanroom, products, processes or personnel at risk. NOTE Informative guidance concerning cleaning requirements listed in 4.6.1 to 4.6.6 can be found in Annex F. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 13 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

Annex A (informative)

Operational systems A.1 General It is essential that management provides leadership that will focus the attention of its staff on generating and maintaining systems that will encourage good cleanroom practices. A management structure should be defined and published to ensure all parties are aware of their responsibilities. Good cleanroom practices will have a significant impact on the quality of products being produced and the processes performed in the cleanroom. This annex is provided to assist management in identifying those systems. A.2 Assessing contamination risks A.2.1 Methods for assessing risks A risk assessment should be made to determine any relevant contamination control factors that may affect the products or processes performed in the cleanroom. Some examples of methods used for determining and managing these factors include: a) HACCP (Hazard Analysis Critical Control Point)[1]; b) FMEA (Failure Mode Effects Analysis)[2][3]; c) FTA (Fault Tree Analysis)[4]. A.2.2 Determining operational risks A.2.2.1 General Improper control of the critical elements of an operational cleanroom can pose a risk to the cleanliness of the cleanroom and the quality of the product. A list of these critical elements and some of the associated risks can be found beginning in A.2.2.2 to A.2.2.6. An assessment of these risks should be carried out and plans formulated by each organization to remedy non-compliant situations. In this assessment, it is especially important to consider the following: a) concentration of contamination in or on the risk factor; b) distance from the risk to the product; c) importance of the method used to protect product from the risk[5]. Information concerning cleanroom support parameters and factors including heating, ventilation and air conditioning functions, pressure, temperature, humidity, air change failure and filter failure are discussed in ISO 14644-2, ISO 14644-3 and ISO 14644-4. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 14 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

A.2.2.2 Cleanroom clothing Risk factors that may influence the operation or environmental quality of the cleanroom include: a) required human containment (coveralls, frocks, hoods, gloves, boots, masks, etc); b) material performance (weave characteristics, filament types, sterility, antistatic, calendering, etc); c) design and construction (special tailoring requirements); d) comfort; e) usage (launderable versus disposable); f) choice of personal clothing worn under cleanroom clothing; g) time interval or number of wearings before laundering is required; h) choice of cleanroom clothing laundry; i) renewing, packaging, storage and distribution. A.2.2.3 Personnel Risk factors that may influence the operation or environmental quality of the cleanroom include: a) selection of personnel; b) education and training; c) safety (including emergency procedure); d) personal attire, hygiene and behaviour, (including behaviour prior to entering the cleanroom); e) chronic and acute medical conditions; f) personnel who shed significantly more contamination than other personnel; g) who is allowed to enter; h) special procedures for visitors; i) maximum occupancy; j) entry and exit procedures; k) movement and activity of personnel within the cleanroom. A.2.2.4 Stationary equipment Risk factors that may influence the operation or environmental quality of the cleanroom include: a) entry and exit procedures; b) installation; c) cleaning techniques; d) contamination generation; Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 15 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

e) generation of heat, humidity and electrostatic charge; f) maintenance and repair; g) cleanliness of process material and utilities delivery systems; h) potential equipment failures. A.2.2.5 Materials and portable and mobile equipment Risk factors that may influence the operation or environmental quality of the cleanroom include: a) compatibility and selection; b) entry, exit and movement procedures; c) storage factors while in the cleanroom; d) contamination factors during use; e) generation of electrostatic charges; f) liquid and gas purity supplied by delivery systems; g) waste disposal; h) packaging. A.2.2.6 Cleanroom cleaning Risk factors that influence the operation or environmental quality of the cleanroom may include: a) routine environmental contaminating factors (airflows, airborne particles, out-gassing, hazardous gas, micro-organisms, vibration, electrostatic charges, molecular contamination, etc.); b) personnel and material flow; c) service, maintenance and repair; d) cleaning methodology; e) emergency and planned shutdown; f) facility expansion and modification; g) frequency for monitoring the results of cleaning. A.3 Monitoring and corrective action A routine monitoring programme should be followed that encompasses personnel, cleaning and other operational systems. Monitoring should be sufficiently frequent and comprehensive to detect actual or emerging unacceptable conditions in a timely manner. Exceeding specified action levels should result in a prompt response, including investigative and corrective action. Investigative and corrective action should include the effect on product quality as a potential result of the non-compliant condition. Further information can be found in ISO 14644-2 and ISO 14644-3 for particle monitoring. Information on microbiological monitoring can be found in ISO 14698-1 and ISO 14698-2. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 16 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

A.4 Education and training A.4.1 Involvement General personnel activity within the cleanroom has a profound effect on the integrity of the clean environment. Failure to properly train anyone entering, using or maintaining the facility will compromise the effectiveness of the cleanroom. Management is therefore responsible for implementing a comprehensive programme to train all personnel with regard to their responsibilities and how those responsibilities interact with the clean environment. Certification should be based on successful completion of testing to demonstrate understanding and compliance. The programme should ensure each of the following groups of personnel is educated and trained appropriately: a) operators; b) technicians; c) engineers and scientists; d) quality assurance personnel; e) supervisors and managers; f) facilities personnel; g) contractors; h) field service personnel; i) visitors. A.4.2 Training course contents Subjects that can be included in the training course include: a) how the cleanroom works (design, airflow and air filtration); b) cleanroom standards; c) sources of contamination; d) personal hygiene; e) cleaning; f) cleanroom clothing procedures; g) maintenance procedures; h) how a cleanroom is tested and monitored; i) how to act in a cleanroom; j) explanation of the work process, technologies or sciences employed and how the process can become contaminated; k) safety and emergency response. A.4.3 Monitoring of cleanroom personnel and corrective action The cleanroom training programme provides an explanation of requirements and actions that minimize the risk factors important to the cleanroom, identified in A.2.2.3. The ability of personnel to incorporate all elements of Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 17 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

cleanroom training into practice is essential to the continuous, effective operation of the cleanroom. Personnel, although properly trained, may not fully comprehend all requirements or may lapse into poor procedural habits. Therefore, actions of personnel listed in A.4.1 should be monitored to ensure personnel carefully comply with correct cleanroom disciplines. Consideration should be given to a system that will monitor cleanroom personnel. Monitoring programmes can be formal or informal depending on the level of empowerment given to each person that is part of the cleanroom staff. Internal auditors can monitor the actions of those in the cleanroom based upon the written procedures. Reports can be issued to management on a regular basis detailing unsatisfactory behaviour and can be used for determining corrective action[6]. An effective programme should be a positive influence on all personnel to follow proper cleanroom procedures. A.4.4 Training documentation A concise, comprehensive system that documents the training progression and level of each individual associated with cleanroom operation and maintenance should be used. The management team should identify each job and set of jobs or responsibilities. This documentation system should be easily accessible to management and periodically reviewed. Basic documentation should include course contents, personnel identification information, training and certification dates, and schedules for retraining that may be required at future intervals. A.5 Cleanroom support services A.5.1 General overview Management is responsible for ensuring cleanroom support services consistently function as designed on a day-to-day basis. Support services may include clean and conditioned air systems, compressed air and gasses, water and other utilities, and other aspects required for standard cleanroom operation. Failure of any mechanical support system can seriously affect the cleanliness and operation of the cleanroom. Records and procedures documenting the operation of the systems that provide and maintain the cleanroom should be readily available. Some of the information required to establish such systems is given in A.5.1 to A.5.6. More thorough coverage of the subjects listed in A.5.2 to A.5.6 is found in ISO 14644-4. A.5.2 Record of the installation This record should contain installation drawings, cleanroom classification including acceptance test results to original specifications, and recommended spare parts lists. A.5.3 Operating and maintenance instructions Operating and maintenance instructions should include an explanation of how the systems work and their influence on room cleanliness. The mechanical and electrical systems within the installation should have a clear set of operating and maintenance instructions. These instructions should describe procedures used to check and inspect all critical components prior to start-up. Emergency shutdown procedures and start-up procedures after unplanned shutdowns should be documented. A.5.4 Performance monitoring Performance monitoring of the installation is essential to demonstrate satisfactory operation. Documented schedules and procedures that specify the required tests and the frequency of testing are needed to demonstrate specified cleanroom classifications. Action plans for non-compliant situations should be defined. A.5.5 Maintenance procedures Unplanned downtime can adversely affect productivity and introduce contamination to the cleanroom. Ongoing performance checks and preventive maintenance should be performed to minimize contamination Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 18 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

that may be caused by unanticipated equipment failures. Repair and maintenance procedures should contain precautions that will help minimize and contain contamination. Tests may also be necessary to ensure that reactivated equipment is clean and in specification before being accepted for reuse. A.5.6 Maintenance records Evidence of effective maintenance requires a documented record involving all maintenance activities. Problem diagnoses, parts replaced, dates, times and personnel performing the maintenance should be documented. Preventive maintenance schedules and charts should be updated as required. Periodic analysis of such records may help in making improvements to the programme and help optimize preventive maintenance schedules. A.6 Upgrading and modifying the cleanroom All upgrades or modifications, including the addition of stationary equipment and changes to floor plans, can affect the cleanliness of the cleanroom. Management should make certain these changes are planned and carried out in a controlled and thorough manner and that requalification of the installation is in compliance with ISO 14644-2 and ISO 14644-4. A record of all changes or modifications should be documented after requalification. All appropriate personnel with responsibilities affected by these changes should be involved and kept informed of progress. Such personnel may include but are not limited to: a) facility engineers; b) manufacturing engineers; c) equipment engineers; d) contamination control engineers; e) process engineers and scientists; f) quality assurance engineers and scientists; g) manufacturing managers; h) contractors. A.7 Safety Normal operation of cleanroom facilities often includes the use of hazardous, toxic or infectious materials. Preventive measures required by statutory regulations must be observed to protect personnel from exposure to these agents. Management should implement and monitor effective systems for protecting the health and welfare of personnel. Good programmes should include the following: a) centralized, readily-available safety data sheets that describe hazardous materials; b) evacuation plans and practice evacuations; c) accident reporting system; d) feedback suggestion systems for personnel; e) appropriate monitoring of potentially hazardous conditions or materials; f) rapid response to emergencies by trained personnel; g) documentation that supports improvements and corrections to safety-related issues. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Annex B (informative)

Cleanroom clothing B.1 Function of cleanroom clothing Personnel disperse fragments from their skin and particles from their indoor, non-cleanroom clothing. This airborne dispersion will vary from person to person and from time to time but can be several million particles per minute and several hundred bacteria-carrying particles per minute. The prime function of cleanroom clothing is to act as a barrier filter that protects product and process from human contamination. Therefore, cleanroom clothing should be made from a fabric that filters the dispersed contamination. Cleanroom clothing should also be designed to envelop a person and not allow significant amounts of unfiltered body emissions to be dispersed into the cleanroom. An effective cleanroom undergarment in combination with cleanroom clothing can provide an additional reduction in dispersion. Although the majority of contamination originates from the skin and non-cleanroom clothing, contamination is also dispersed from the surface of cleanroom clothing fabrics. The fabric used to manufacture cleanroom clothing should not add to the contamination burden. Personnel also emit inert and microbe-carrying particles from the mouth through sneezing, coughing and talking. Therefore, cleanroom clothing should be made from a fabric that filters the contamination dispersed. Touching will transmit contamination from the hands to surfaces in the cleanroom. Depending on the cleanroom function and class, it may be necessary to wear face masks, helmets and gloves to minimize transmission of these types of contamination. The choice of cleanroom clothing will vary according to the product cleanliness and process requirements but will normally, but not exclusively, consist of hoods, caps, helmets, coveralls, overboots, face masks and goggles or safety glasses. B.2 General choice of cleanroom clothing The best design of cleanroom clothing will completely envelop the person and have good closures at the wrist, neck and ankle. The choice will depend on the class of cleanroom but cleanrooms with higher cleanliness requirements are typified by a one-piece coverall, overboots and a hood with yoke or skirt that tucks under the neck of the garment.[8] Increasing technical requirements on cleanroom clothing may result in increasing personal restrictions or discomfort. Therefore, consideration should be given to what is necessary for the standard of room cleanliness. Where cleanliness and process requirements permit, clothing of lesser coverage may be acceptable[7] [8] [9] [10]. Certain separative devices with built-in clean air systems (e.g mini- environments or isolators) may allow for the simplification of required cleanroom clothing. There are two broad categories of clothing used in cleanrooms: 1) disposable (or limited use) and 2) reusable. In general, disposable or limited use clothing usually is made from a non-woven materials and is used either once or a few times, and then discarded. Reusable cleanroom clothing is processed at regular intervals and usually made from tightly woven synthetic fabrics, constructed with lint-free, continuous filament materials (such as polyester or polyamide). Natural fabrics made from fibres, such as cotton, would not normally be used in cleanrooms as they easily break up and disperse contamination. More critical applications may require the use of membrane barrier technology, which may be either disposable or reusable. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 20 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

B.3 Properties of fabric B.3.1 Barrier properties The fabric used in cleanroom clothing should prevent personnel-generated contamination from being dispersed into the cleanroom. Woven fabric acts as a filter; effectiveness is related to the tightness of the weave of the fabric. In the case of barrier-type fabrics such as non-wovens and laminate membranes, the effectiveness to contain contamination is a function of the barrier characteristics. Fabric effectiveness can be assessed by a measurement of air permeability, particle retention and pore size [8] [10] [11] [12]. As air permeability decreases, there is a corresponding increase in pressure within the garment as personnel move about. This can result in an outward pumping action of unfiltered air through the closures of the cleanroom clothing. B.3.2 Durability Cleanroom clothing should be resistant to breakdown and tearing. The fabric should disperse the minimum of particles. Information is available on tests used to assess these types of fabric properties [7] [10] [13] [14]. B.3.3 Electrostatic properties In some types of cleanrooms (e.g. microelectronics or rooms with flammable or explosive chemicals), the electrostatic charges that build up on the surface of clothing will be harmful to the components being manufactured or hazardous to operators. Fabrics are available with woven-in, static-dissipative threads to discharge any induced voltage potentials on the fabric surface. The effectiveness of a fabric to dissipate an electrostatic charge can be indirectly measured by checking the fabric’s surface resistivity. Such methods are described in other sources [10] [15] [16]. In a more effective test, a static charge of known voltage level is applied to the fabric. Static dissipative performance can then be determined by the time it takes for the voltage to decrease by a given percentage of the original voltage. Such methods are described in other sources [10] [15] [16]. B.3.4 Other physical properties The effectiveness of a fabric will deteriorate due to aging, wear, washing, drying, sterilization, etc. This deterioration should be monitored. Another physical property that should be considered is the resistance of the fabric to chemicals, such as those used during the manufacturing process and in the cleaning and disinfection of the cleanroom and clothing. NOTE The tests referenced in B.3.1 to B.3.4 will help to verify that the clothing remains effective. B.4 Design and construction of cleanroom clothing B.4.1 Construction of clothing Cleanroom clothing should be constructed to minimize contamination in the cleanroom. Cutting the fabric prior to sewing produces raw edges that will generate particles if left unfinished. Methods used to finish these edges are as follows: all raw edges of the fabric should be covered, interlocked and heat seared or laser cut to prevent fraying. Seams should be double-needle stitched, bound or taped to provide a good barrier and not produce fibres. Threads should be synthetic continuous filament. Zippers, clips and fasteners, and shoe soles should not shed, chip or corrode, and should stand up to multiple launderings and where necessary, sterilization [8]. B.4.2 General design The selection of the design of clothing should be considered with respect to the type of cleanroom [8] [9] [10]. Cleanroom clothing should incorporate a large selection of sizes to provide comfort and fit. To minimize the retention of contamination, pockets, pleats, darts, hook and pile fasteners, and action backs should not be Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 21 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

used. Elasticized or knitted cuffs should not trap or shed contaminants and should not build up electrostatic charges. Cleanroom clothing closures should provide a tight yet comfortable closure. Other design parameters that should be considered are: a) zipper material (e.g. covered plastic zip-fasteners), type and location; b) placement and effectiveness of snap adjusters and stays; c) sleeve construction (set-in or raglan); d) cuff closures (elasticized, knit or snap) e) collar style; f) ability to put cleanroom clothing on over various shoe or boot styles; g) hood style (open or closed face, snap or pull-over); h) passive or active adjustment and fit of hoods; i) type and placement of straps on boots. B.4.3 Dispersal chamber (body box) This simulation procedure can be used to demonstrate the combined effect of fabric, construction and design of clothing. A person will enter the box, which is ventilated at a known flow rate of filtered air, and exercise to a given routine. The number of particles or bacteria dispersed can be measured. Different types of clothing that have to be assessed can be compared. A description of this test is available [8]. B.5 Thermal comfort Whenever possible, the comfort of people working in the cleanroom should be considered when choosing cleanroom clothing materials [17]. Air and water vapour permeability specifications of the fabrics under consideration can help in this determination [8] [18] [19]. A simple but effective approach is to obtain a selection of suitable clothing of different fabrics and try them in the cleanroom. Feedback, solicited from personnel who will be expected to wear the clothing, may provide valuable information that will aid in the selection process. The use of relevant personnel parameters and environmental parameters (air temperature, velocity, turbulence, mean radiant temperature, and humidity within the cleanroom) can be used to derive theoretical clothing comfort level according to ISO 7730 [20] which provides guidance and tables that will assist in making this determination. B.6 Cleanroom clothing cleaning process and frequency of change During use, cleanroom clothing will become contaminated. If it is to be reused it should be cleaned. Suggestions as to how this cleaning process should be carried out are available in other sources [8] [21]. Final treatment and packaging operations for cleanroom clothing should be carried out in cleanroom conditions that are compatible with the standards of the cleanroom in which they will be used. Clothing similarly becomes contaminated with bacteria. In cleanrooms where bacteria are an important consideration, the processing cycle in the cleanroom laundry should include, as appropriate: a) disinfection; b) hot water cycles; c) sterilization. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 22 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

Cleaning procedures should include sample testing at the laundry for the appropriate type and level of contamination. The frequency of clothing change will vary according to the intended use of the cleanroom. The more sensitive the process is to contamination, the more frequently the clothing should be changed and cleaned. However, increasing the cleaning frequency will cause additional stress to the cleanroom clothing, contributing to premature breakdown of the fabrics. Guidance is also available to help in the decision-making process [8]. B.7 Gloves Cleanroom gloves are required in most cleanrooms. They cover that part of the human body that is often closest to the product and critical surfaces. Consideration should therefore be given to whether gloves are necessary. If they are used, consideration should be given to what properties are best suited, as well as how often they should be changed or cleaned (and where appropriate, disinfected). Properties of cleanroom gloves that should be considered with respect to the type of cleanroom in which they will be used are as follows: surface contamination, outgassing, sterility, tactility, strength, comfort, fit as well as the method of packaging. Various tests can be performed to help in selecting the proper gloves for each particular cleanroom application.[22] Gloves can be constructed of latex, vinyl, polyurethane, or other materials such as nitrile rubber. The choice of construction should be considered with respect to the required properties and application of the glove, and the cost. Undergloves, made from non-linting materials, may also be needed by some employees to provide a level of comfort or isolation from inner glove surfaces that can cause or aggravate contact dermatitis. The cleanliness of outer surfaces of cleanroom is extremely important. A method should be devised for storing and removing gloves from their packaging and putting them on so as to minimize contaminating the outer glove surfaces. B.8 Face masks and other headgear Face masks and exhaust headgear provide a barrier against saliva and contamination dispersed from the mouth, nose, face and, in the case of headgear, the head. Masks and veils are passive barrier elements commonly used in cleanrooms. The masks can be surgical-style masks with tie straps, elasticized straps or loops. Face veils have headbands or snaps or can be permanently sewn into cleanroom hoods at manufacture. Materials used are washable and disposable fabrics. Care should be taken to select the proper material and style that is appropriate to the risk from emissions from the mouth. This selection should also consider the acceptability of the face mask to the personnel. Headgear is available that provides an active barrier to contamination from the mouth and head. A helmet with hood and clear face-shield encloses the head and is provided with a filtered exhaust system that prevents contamination from escaping into the cleanroom. Glasses or goggles can help provide an additional barrier to help retain skin flakes and eyelashes and keep them from falling onto critical surfaces. Glasses or goggles should be constructed from materials that are cleanroom compatible and should conform to accepted personal safety standards. B.9 Storage of clothing B.9.1 If the cleanroom clothing is to be reused, it should be stored or hung using appropriate techniques that will maintain the cleanliness of the clothing. Clothing elements may require physical separation when stored. Launderable or disposable bags can be used to help avoid cross-contamination. Several methods are effective for storing clothing. These may include: Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 23 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

a) clothing racks with high-efficiency, self-contained, filtered air supply; b) fixed and portable racks utilizing hangers; c) locking and non-locking hooks mounted to walls or frames in the changing area or room (either in a locker or in the room); d) bins or storage slots. B.9.2 The space required to temporarily store cleanroom clothing used by personnel currently working in the cleanroom is dependent upon the number of people working in the cleanroom and the frequency at which the cleanroom clothing is changed. B.9.3 An area large enough to contain the total inventory of packaged cleanroom clothing should be set aside for storage purposes. Lockers can be obtained for this purpose. These lockers should be placed on the cleaning schedule to ensure that they do not contribute to contamination. B.9.4 Cleaned clothing should be packaged in clean, non-shedding bags to avoid contamination during handling, storage and distribution.[8] The shelf life for sterilized products should be defined. It is recommended that storage should be in a controlled environment that is adjacent to or in the changing area. This allows better control of the inventory and reduces the risk of clothing being removed from the cleanroom environment and becoming soiled. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 24 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

Annex C (informative)

Personnel C.1 Training Only trained personnel should be allowed to enter and work in a cleanroom. All personnel should be given an introductory course when initiated into the cleanroom and further periodic retraining (see A.2). C.2 Access by personnel People generate contamination. Therefore, only essential personnel should enter the cleanroom. If the total number of people allowed in the cleanroom is controlled, access should be documented and enforced. Visitors and maintenance people can be allowed into the room by permission and under supervision. They should be given an appropriate level of training. C.3 Clothing and personal items The type of clothing worn under cleanroom clothing will affect the dispersion of airborne particles and fibres. Personal indoor clothing manufactured from natural fibres such as wool or cotton and worn underneath cleanroom clothing will shed contamination. The provision for special cleanroom undergarments should be considered. If underclothing is provided, they should be made from closely woven, artificial fibres such as polyester for effective filtration of body contaminants. Personal items should be left outside the cleanroom in a secure area. Jewellery, such as rings, watches, and chains, can puncture cleanroom gloves or dangle outside face masks, hoods or sleeves of the clothing, and should be avoided. Cosmetics, talcum powder, hair sprays, nail polish or similar materials are undesirable in a cleanroom. An assessment should be made of the risk to the product or process from these types of items. Cosmetics can generate particles that contaminate cleanroom clothing, the cleanroom and products being produced and may be prohibited. C.4 Hygiene Cleanroom personnel are expected to have good personal hygiene. Personnel should keep dandruff controlled, and, as necessary, use specially formulated skin lotion to replace skin oils after washing and showering. Personnel arriving for work should report problems that might increase contamination in the cleanroom, including the following: a) conditions such as flaking skin, dermatitis, sunburn or bad dandruff; b) cold, flu or chronic coughing; c) allergic conditions that cause sneezing, itching or scratching; d) in a biocleanroom — high microbial bioburden on personnel. Depending on the seriousness of the condition with respect to the process or product being produced, it may be necessary to reassign personnel with such conditions to work outside the cleanroom until the condition is in abeyance. In some cleanrooms, it may be required that personnel refrain from smoking for a defined period of time before entering. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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C.5 Cleanroom clothing changing procedures Cleanroom personnel will change into cleanroom clothing before proceeding into a cleanroom. A method should be adopted to put on and remove clothing to minimize contamination of the outside of the cleanroom clothing and to ensure contamination is not spread from the changing area. Several methods are acceptable depending on the design of the changing area and the standard of cleanliness of the cleanroom. Further information is described in other sources. [5] [6] [23] Usually the process begins at the head and proceeds downward to the feet:

  1. Remove contamination from shoes by use of a shoe cleaner, cleanroom mat or cleanroom flooring.
  2. Remove unnecessary street clothing.

  3. Remove jewellery, etc. if required.

  4. Remove cosmetics and put on moisturizer, if required.

  5. Put on hair cover, if applicable.

  6. Wash hands and put on suitable moisturizer, if applicable.

  7. Put on cleanroom underclothing, if applicable.

  8. Put on cleanroom-dedicated under-shoes, or shoe covers.

  9. Select cleanroom clothing.

  10. If required, put on gloves for handling cleanroom clothing.
  11. Put on face and head covering.
  12. Put on coverall or gown.
  13. Put on shoe coverings or special cleanroom shoes, using a crossover bench.
  14. Using a full-length mirror, ensure that all items of clothing are properly adjusted.
  15. Gloves used for putting on cleanroom clothing can now either be removed, or left on, so that process gloves can be put on.
  16. Enter the cleanroom. NOTE The previous list of steps outlines one typical procedure that is commonly used, but many variations exist to comply with contamination control needs for certain types of cleanrooms. The way cleanroom clothing should be taken off when leaving the cleanroom will depend on whether fresh clothing is used on each entry or whether the clothing is to be reused. Methods for removing cleanroom clothing that will be reused are described in other sources [17]. Special storage methods can be used if the clothing is to be reused and are described in other sources. [5] [6] [17]. Cleanroom clothing should not be removed from the controlled environment except for transfer to the laundry for cleaning. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 26 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

C.6 Discipline and conduct Cleanroom personnel should conduct themselves in a cleanroom in such a way as to minimize the possibility of contaminating the product. The following are minimum disciplines that should be considered (more information can be found in other sources. [6]  Doors should not be opened and closed quickly, nor left open.  When using a transfer area, the entry door should be allowed to close and the air to purge or stabilize for a predetermined period of time before the exit door is opened into the next area.  Personnel should not position themselves between clean air supplies and product or process surfaces. Doing so will increase the risk of dispersing particles onto product or process surfaces. In general, the correct positioning sequence should be: air supply to exposed product to personnel and then to the general cleanroom area and the air return or exhaust.  Methods should be devised for moving or manipulating the product. “No-touch” techniques should be used where appropriate.  Personnel should not support material against their bodies or contamination may be transferred.  Personnel should not talk when working close to the product.  Personnel should not allow anything to trail over the product.  Nose blowing should be done outside the cleanroom. Gloves should always be changed afterwards.  Personnel should also refrain from touching, scratching or wiping any skin areas while in the cleanroom. Doing so may require personnel to return to changing area to obtain and put on fresh gloves.  Glove and cleanroom clothing surfaces can easily become contaminated. Personnel should not touch contaminated surfaces that will transfer contamination to critical areas. Each cleanroom must have a policy that instructs personnel to return to the changing area to change into clean gloves or cleanroom clothing. Some cleanrooms may allow gloves to be changed in the cleanroom.  A cleanroom wipe should be used as specified and then discarded in the proper waste receptacle.  All personnel movements should be deliberate and methodical. Rapid walking and movements or over- exuberant behaviour should not be allowed since it will disrupt the airflow. This will both generate contamination and allow it to be included in the air stream.  The room should be kept neat and tidy.  Products stored or left standing in a cleanroom should be protected from contamination and kept in an identifiable closed cabinet, container or unidirectional cabinet.  Waste material should be placed into easily identifiable containers and not allowed to collect unnecessarily. C.7 Safety C.7.1 Preventive measures required by statutory regulations must be implemented to protect personnel from hazards that may occur or may be in use in the cleanroom, such as microbes, radioactivity and chemicals. The use of containment cabinets, cupboards or isolators may address these concerns. Information on preventive methods is discussed in ISO 14644-4 and ISO 14644-7. Suitable protective clothing such as eye splash shields, gloves and aprons may be required. Local regulatory authorities may recommend or require additional measures to protect the safety of personnel in cleanrooms. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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C.7.2 Emergency situations may arise and emergency response personnel, trained in all aspects of potential emergencies, can minimize the effects of mishaps that may occur. All employees should be trained for an orderly evacuation. If an evacuation is necessary, provisions should be made for the orderly return to the cleanroom once the situation is cleared. An emergency procedure for supplying fresh cleanroom clothing should be implemented. C.8 Personnel initiatives Elements for formal monitoring and corrective action programmes are described in A.7. However, personnel should understand that they could have a positive influence on the effectiveness of the cleanroom. Helpful coaching of one to another can have a positive effect on conformance to personnel procedures. Personnel should be encouraged and empowered to immediately report any observed deficiencies, whether personnel or facility related, to individuals responsible for cleanroom integrity. Such action will allow otherwise unnoticed contamination sources to be corrected before the problem becomes serious enough to place products or process at risk. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Annex D (informative)

Stationary equipment D.1 General Equipment that is large enough to be stationary or relatively immovable, once located within the cleanroom, is discussed in this section. Stationary equipment often surrounds, envelopes, or encloses the products or processes for which the cleanroom was provided. Stationary equipment may be in the form of automated and mechanical processing equipment, separative devices, and exhaust hoods as well as other large equipment. Usually, extensive efforts are required to remove or relocate this equipment once installation is completed. When possible, equipment to be used in the cleanroom should be manufactured under clean conditions and packaging procedures should be adapted for the requirements of the intended cleanroom. D.2 Clean entry process D.2.1 Planning The process of bringing equipment into the cleanroom should not add contamination. Equipment entering a cleanroom that is “as-built” or “at-rest” should be properly unpacked and cleaned. Failure to do so will require extensive cleanup afterwards. However, special considerations should be made before bringing equipment into an “operational” cleanroom. Failure to do so will expose not only the cleanroom to contamination risks but may affect products in process. This will also necessitate additional cleaning and may require the cleanroom to be requalified under ISO 14644-2. An appropriate strategy should be developed to avoid problems. Guidance is given in D.2.2 and D.2.3 and in other sources. [6] D.2.2 Inspection and removal of non-cleanroom packaging All equipment should be checked for damage in transport. Suspected or damaged goods should be isolated or protected outside the cleanroom pending appropriate actions. Whenever possible, shipping crates and packaging should be removed in the uncontrolled environment adjacent to the cleanroom. All cardboard and heavily shedding materials should be removed before being transported into the controlled environment. When not pre-packaged, all surfaces of the equipment should be pre-cleaned prior to entry of the equipment into a cleanroom area. This cleaning is best carried out within the specific transfer area used for equipment entry If the equipment is so large that special installation procedures are required, the area should be isolated from surrounding cleanrooms or other controlled environments through the use of temporary walls. D.2.3 Removing cleanroom packaging Unpacking of equipment should be done in steps to control contamination entering the cleanroom. A controlled transfer room, or a temporary room built for this purpose and attached to the cleanroom, can be used for the removal of exterior film packaging materials and surface cleaning before cleanroom entry. The following is an example of the steps that should be taken during unpacking:

  1. The outer protective covering should be vacuumed, beginning at the top surface and then proceeding to the sides.
  2. The protective cover should be wiped, using the appropriate cleaning agent. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 29 --- ISO 14644-5:2004(E) © ISO 2004 – All rights reserved

  1. The outer layer of packaging film should be slit at the top in an "Ι" form and peeled from the top to the bottom edge. The bottom edge of the packaging film should then be lifted and joined to the sides of the packaging film.
  2. The unpacking procedures in steps 2 and 3 should be repeated for each additional layer. All exterior surfaces of the equipment should be thoroughly cleaned.

  3. All personnel should be wearing the proper cleanroom clothing prior to entering the transfer area from the cleanroom.

  4. All moving and handling equipment should also be cleaned, in accordance with procedures described in D.3.

  5. The transfer area should be cleaned before opening the doors to the cleanroom for transferring the equipment inside. D.3 Transporting equipment Large equipment should be dismantled (if possible) to a size that will enable safe entry, minimizing risk to personnel and the existing cleanroom. Physical damage and contamination can result when these large units come into contact with fixed surfaces and other tools. Any special equipment used for lifting, hauling or positioning large equipment should be thoroughly cleaned before being allowed into the cleanroom. Often, this equipment may not be designed or maintained for cleanroom use and should be thoroughly inspected for chipping and flaking surfaces or for materials unsuitable for transfer into the cleanroom. These tools can often be made acceptable by means such as wrapping and sealing the tool with cleanroom-compatible plastic films and tape. Soft rubber wheels can be coated with cleanroom tape to avoid leaving trails of rubber or plastic particles on the flooring. D.4 Installation procedures The method used to install equipment will depend on how the cleanroom has been designed and used. Ideally, the cleanroom should be closed down during the installation and a sufficiently wide door or pre- engineered access panel provided to bring the new equipment into the cleanroom. Preventive measures should be taken to avoid contaminating the adjacent cleanroom area during the installation period. This will simplify the subsequent cleaning and testing needed to ensure that the cleanroom is within its cleanliness specification. If work within the cleanroom must continue during installation, or structural demolition is required, then the rest of the operational cleanroom must be effectively isolated from the work area. Surrounding the equipment with a temporary isolation wall or partition can do this. An area should be left around the equipment to complete the installation unhindered. a) Access to the isolation area should be from a service aisle or other non-critical area, if possible. If access is not possible, measures should be taken to minimize the effects of construction-generated contamination. Airflow to this isolation area should be maintained at a neutral or negative pressure to reduce the possibility of contamination being forced outside the work area. b) A completely sealed isolation area should not be pressurized from within or the possibility of contaminating the surrounding cleanroom exists if a penetration of the barrier should occur. The clean-air supply inside the isolated area should be blocked to avoid pressurizing the surrounding cleanroom. When entry to the isolated area is only accessible through an adjacent cleanroom, sticky mats should be installed to remove shoe-borne contamination. Once inside, disposable boots or shoe covers and coveralls may be required to avoid contaminating cleanroom clothing. These disposables should be taken off before leaving the isolated area. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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c) A method and frequency for monitoring the areas surrounding the isolated area should be instituted to ensure that any contamination that may leak into the adjacent cleanroom areas is detected. d) All facility services, such as electricity, water, gas, vacuum, compressed air and waste piping, will then be attached. Care should be taken to ensure fumes and debris generated by this operation are controlled and contained as completely as possible to avoid inadvertent release to the surrounding cleanroom and facilitate effective cleaning before removal of the isolation barriers. e) Accepted cleaning procedures (see Annex F) should then be used to decontaminate the entire isolation area. All surfaces should be vacuumed, wiped and mopped, including all walls (both fixed and portable), equipment and floors. f) Special care should be taken to clean areas behind equipment panels and under equipment. g) Some internal preparation and preliminary performance testing of the equipment is now possible, but final acceptance may require full cleanroom conditions before final testing can be completed. h) The isolation walls can now carefully be removed and filtered air sources returned to service if deactivated. This step should be scheduled to minimize interruptions in the regular operation of the cleanroom. Particle measuring or testing may also be required. i) Equipment interiors and critical processing chambers should be cleaned and prepared for use under normal cleanroom conditions. j) All appropriate inner chambers and all surfaces coming into contact with the product or involved in the handling of the product should be wiped to achieve a desired cleanliness level. The cleaning procedure should be carried out, by working from the top to the bottom of the equipment, as once particles are disturbed, gravity will force larger particles to fall to the bottom of the equipment or to the floor. k) Clean the outer surfaces of the equipment, working from the top to the bottom surfaces. l) If necessary, surface particle checks should be performed in areas critical to product or process requirements. D.5 Maintenance and repair With time, equipment wears out and becomes dirty or emits contamination unless it is maintained. Preventive maintenance should be carried out to ensure equipment is not allowed to become a source of contamination. Maintenance and repair of equipment should proceed without contaminating the cleanroom. [24] [25] Successful completion of such repairs should include decontamination of external surfaces. Decontamination of internal surfaces may also be needed, if required by the process. The equipment should not only be in working condition, but steps should be taken to decontaminate internal and external surfaces consistent with processing requirements. The following measures can help to control contamination generated by maintenance of stationary equipment. a) Equipment being repaired should be removed from the area whenever possible before making repairs to reduce the possibility of generating contamination. b) If necessary, stationary equipment should be suitably isolated from the surrounding cleanroom operations before proceeding with major repairs or maintenance. Alternatively, steps should be taken to ensure that all products under manufacture have been removed to a suitable location. c) Adjacent cleanroom areas near the equipment being repaired should be suitably monitored to insure that contamination is being effectively controlled. d) Maintenance personnel working in the isolated areas should not come into contact with personnel performing manufacturing or processing procedures. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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e) All personnel repairing and maintaining equipment in cleanrooms should follow the appropriate practices defined for the area, including wearing appropriate cleanroom-approved protective clothing, and cleaning the area and equipment after repairs are completed. f) A determination of conditions should be made before technicians lie or crawl under equipment to make repairs. Conditions caused by chemicals, acids or biohazards should be effectively neutralized before proceeding. g) Steps should be taken to protect the cleanroom clothing from undue contact with contamination from lubricating oils or processing chemicals. Rips and tears from sharp edges should also be avoided. h) All tools, boxes and carts used for maintenance or repair work should be thoroughly cleaned before being exposed to the cleanroom environment. No rusted or corroded tools should be allowed. Sterilization or disinfection may be necessary in a biocleanroom. i) Technicians should refrain from setting tools; spare, damaged parts; or cleaning materials on adjacent or nearby work surfaces used for product and process materials. j) Care should be taken to clean as repairs proceed so that contamination does not build up. k) Gloves should be changed regularly so they do not deteriorate and permit bare skin to touch clean surfaces. l) When gloves other than cleanroom gloves (e.g. acid-, heat- or cut-resistant types) are required, they should be either cleanroom compatible or covered with a pair of cleanroom gloves. m) Vacuum cleaners should be used during all drilling or sawing operations. Maintenance and construction operations often require drilling or sawing. Special shrouds can be used to contain the tool and area being drilled or sawn. Open spaces remaining after holes are drilled in floors, walls, sides of equipment or other such surfaces should be properly sealed afterwards to prevent contamination from entering the cleanroom. Methods for sealing may include use of caulks, adhesives and specially fabricated plates. When maintenance is complete, it may be necessary to verify the surface cleanliness of the equipment that was repaired or maintained D.6 Equipment removal Removing stationary equipment from the cleanroom often stirs up or loosens contamination from internal or other inaccessible surfaces that have not been routinely cleaned. This is especially true when the equipment must be disassembled before removal. Steps should be taken to isolate, clean, and contain such equipment before and during removal to avoid contaminating the surrounding cleanroom. Regulatory considerations may be involved if the contamination is of a hazardous nature. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Annex E (informative)

Materials and portable equipment E.1 General Items that can easily be transported into and out of the cleanroom can compromise the cleanliness of the cleanroom if they are not properly selected, handled and stored in the correct quantities. This includes consumable and disposable supplies, and production and cleaning materials, as well as hand tools and portable equipment. The ability to sterilize or disinfect reusable materials and portable equipment should be considered in biocleanroom applications. E.2 Criteria for selection E.2.1 Characteristics To protect a cleanroom from contamination, materials should have the following characteristics:  surfaces and moving parts that shed or generate as little contamination as possible;  unbroken, impervious and clean surfaces, although there are necessary exceptions, such as cleanroom wipers;  properties that minimize generation of contamination by shedding and cutting;  suitable cleanroom packaging;  compatibility with the cleanroom environment. E.2.2 Other criteria The following additional criteria should be determined according to the purpose and usage within a cleanroom:  free from undesirable chemicals (e.g. acid, alkali, organic);  acceptable anti-static properties;  low outgassing properties;  free from micro-organisms;  compatible with sterilization or disinfection procedures in biocleanrooms. E.3 Preliminary testing Preliminary testing and auditing should be performed as agreed upon between customers and suppliers. Testing procedures performed by the supplier may be deemed sufficient for entry and use in the cleanroom. However, certain applications may require that additional testing be performed before some materials are brought into or used in the cleanroom. Incoming inspection criteria and sampling methods should be fully documented. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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A secure storage location may be necessary to avoid unauthorized use while materials are waiting for acceptance. Strict quarantine measures may be necessary for biologically sensitive materials. Test equipment and methods should be fully documented. Acceptance limits and authorized personnel should be identified for final approval or disposition of non-conforming materials. A procedure for communicating problems to the supplier should be instituted. The supplier should be expected to react with plans to improve its quality and avoid further shipment of non-conforming materials. The supplier should notify the customer prior to making critical changes to approved materials or supplies used in the cleanroom. Evaluation methods and technologies should be reviewed periodically. Some incoming inspections may be eliminated when data show that the supplier has a proven quality record. E.4 Entry and exit procedures E.4.1 Unpacking and entry procedures Carrying materials into the cleanroom should not contribute contamination to the cleanroom. Materials and supplies that are carried into the cleanroom are subject to procedures similar to those described in Annex D. Only materials and portable equipment that are compatible with the cleanroom classification and use should be brought into the cleanroom. Outer contamination-generating packaging, such as wood, cardboard, paper and other materials, should be removed before entry to any part of the controlled or cleanroom environments. Inner plastic wrappers should not be removed at this time. Any interior packaging should be wiped with appropriately moistened cleanroom wipers to remove any gross contamination from the outer packaging before being carried into the controlled environment or specific area used for removing cleanroom packaging. Various types of non-wrapped portable equipment require careful cleaning before entering the cleanroom and are discussed in E.5. A designated transfer area, adjacent to the cleanroom, should be used for final wiping procedures. The changing area should be avoided for this purpose to avoid contaminating cleanroom clothing. A working surface and wiping materials should be readily available in this location for the task of cleaning all outer surfaces of the object to be transported into the cleanroom. The outer wrappers of double-wrapped packaging can now be removed and placed in an appropriate rubbish receptacle. Final packaging should only be removed prior to use of the material or object. Any wheeled, portable equipment, including carts and trolleys, should be thoroughly cleaned before being allowed to enter the cleanroom. Cleaning efforts should not overlook the surfaces of wheels that can transfer excess contamination directly onto the cleanroom floors. Sticky mats or flooring will help prevent this from occurring. Cleanroom personnel, correctly dressed in cleanroom clothing, may enter the transfer area from the cleanroom side and carry such items into the cleanroom. A clean cart or trolley should be used to transfer numerous or large items into the cleanroom. E.4.2 Entry of materials through pipes Materials such as bulk chemicals, compressed gasses and water generally enter the cleanroom through pipes. Such materials are subject to the procedures that govern the introduction and intended use of those materials to the facility. E.4.3 Exit procedures for materials and portable equipment E.4.3.1 Personal and small equipment Many items used by personnel are routinely removed when personnel leave the cleanroom. These items may include notebooks, pens, hand tools and other types of small portable equipment. These items should be protected from becoming contaminated through the use of approved plastic bags or other suitable means. This procedure will facilitate re-entry to the cleanroom at a future time. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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E.4.3.2 Waste Materials Certain waste materials and portable equipment may have a higher risk of transferring contamination to personnel and their clothing. Steps should be taken to completely contain any such materials before transport and arrangements made to thoroughly clean such areas before personnel or processing is allowed to continue. Such objects should preferably leave the cleanroom (after being packaged) via transfer areas for material rather than via changing rooms for personnel. E.5 Types of materials and portable equipment E.5.1 General Materials designated for use in the cleanroom should conform to desired cleanliness levels. Considerations vary according to the desired use in the cleanroom and should be selected to control cleanroom contamination and protect the process during use. Many items typically used in cleanrooms are listed in E.5.2 to E.5.18. E.5.2 Cleanroom clothing materials Cleanroom clothing materials are described in Annex B. E.5.3 Solutions and finishes used in cleaning Cleaning solutions are used to aid in the removal of contamination from surfaces in the cleanroom. Some particles are floated off by the cleaning solution and others are pushed off through use of a wiper. After cleaning, certain finishes are also used to protect or preserve characteristics of surfaces in the cleanroom. These solutions and finishes should be as clean as required to meet the particle requirements of the cleanroom. The filtration of pre-packaged solutions should be considered. The following are types of cleaning solutions and finishes: a) Clean-filtered, distilled or deionized water has many desirable properties but such water can corrode certain types of surfaces and may be ineffective in cleaning without the addition of a surfactant or disinfectant. b) Surfactants and detergents are the most reasonably priced, non-toxic, non-flammable and effective cleaning agents. However, non-ionic surfactants are generally preferred for cleaning cleanrooms as this group is the least reactive and does not contain metallic ions. c) Organic solvents can also be used for removing contamination on hard surfaces. Organic films are best removed with organic solvents or detergents. (Detergents tend to leave behind a film.) d) Disinfectants are used to kill micro-organisms. Care should be taken to select an appropriate material that will not contaminate the process or become harmful to personnel or equipment [26]. e) Synthetic sealers that are highly resistant to wear can be used on certain cleanroom floors. Antistatic floors require special care and sealers should not compromise the surface or electrical characteristics. Any sealing operations should only be done when cleanroom manufacturing is stopped or during general maintenance periods. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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E.5.4 Wipers Wipers are used to remove contamination from surfaces in the cleanroom. Unfortunately, there is no single perfect wiper that suits every application within the cleanroom. Some wipers are absorbent but shed particles or fibres; others don't shed but do not absorb. Information on the selection of wipers is described in other sources. [10] [27] [28] The needs of the application should be considered and an appropriate evaluation should be performed. The following characteristics should be considered when selecting wipers for cleanroom use: a) wiper material; b) solution or solvent compatibility; c) absorption rate of liquids; d) particle generation (both wet and dry); e) extractable molecular contamination; f) sterilization compatibility, if necessary; g) packaging. E.5.5 Vacuum cleaners, hoses and handles The selection and use of cleanroom-compatible vacuum cleaning equipment is important for an effective contamination control programme. a) Portable vacuum cleaners are constructed of stainless steel or plastic. All outlet air must flow through a terminal HEPA or ULPA filter before being allowed to escape to the surrounding environment. Vacuum cleaners capable of handling damp and liquid materials are also available for the cleanroom. b) Built-in vacuum cleaner systems employ a large, centralized vacuum pump, usually in a service area outside the cleanroom environment, which is connected by a system of plastic piping to wall outlets in each area of the cleanroom. c) Hoses, handles and tools should be matched to the application and constructed of cleanroom-compatible materials. d) Arrangements should be made for routine inspection and maintenance of all equipment used in the vacuum cleaning process. The HEPA or ULPA filters of the vacuum cleaning equipment should be tested and/or replaced on a regular basis to ensure that they do not become a source of airborne contamination in the cleanroom. E.5.6 Mops Standard commercial or industrial grade mops and handles should not be used within the cleanroom environment (including changing and other controlled areas). Mops should be carefully selected to resist shedding of fibres and the effects of sterilization, if so required. Floor mop heads should be constructed of polyester fibres or open-celled hydrophilic (synthetic) materials. Block or sponge mop heads should be constructed of open-celled hydrophilic (synthetic) sponge material. Handles and fittings should be made of stainless steel, anodized aluminium, fiberglass coated with polypropylene, or other non-shedding plastics and should be compatible with the operation of the cleanroom mops. Roll mops (similar to paint rollers) with a slightly sticky surface may be used when appropriate for removing contamination from wall surfaces without applying any moisture. Roll mops are available in both renewable and disposable forms. When purchasing synthetic mops or handles, one should be cognizant of the intended cleaning application. Polyvinyl acetate (or equivalent) mop heads are acceptable when used with aqueous cleaning solutions. However, the mop heads will prematurely deteriorate when used with cleaning agents containing high levels of isopropyl alcohol. Some materials used in handles or mop heads are not compatible with steam sterilization. Polyester offers better resistance to autoclaving than polyvinyl acetate. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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E.5.7 Buckets and wringers Buckets or containers with wringers that are compatible with the cleanroom operation are required for wet or damp cleaning operations. The buckets or containers should be constructed of plastic or stainless steel (not galvanized). Stainless steel buckets can be repeatedly autoclaved. The wringer system used in mopping should be compatible with the style and material of the mop head. E.5.8 Floor scrubbers, buffing and waxing machines Standard commercial floor scrubbers or buffers should never be used within an operating cleanroom, as the process would contaminate the environment. Special machines designed for scrubbing cleanroom floors are available. These machines have special shrouds and built-in HEPA or ULPA filtered vacuum cleaners to control contamination redistribution. They also have HEPA or ULPA filtered exhaust casings for the motor chambers. Careful evaluation for cleanroom and flooring compatibility should precede the use of such equipment. Waxes and other non-permanent sealers flake off and cause contamination with traffic and therefore any equipment used to apply or buff such finishes are never recommended. For specific types of flooring refer to ISO 14644-4. E.5.9 Stepladders Stepladders should be of stainless steel, anodized aluminium or reinforced fibreglass and should not leave the cleanroom-controlled area. They should be thoroughly cleaned (disinfected or sterilized if necessary) before entry. E.5.10 Brooms or brushes Brooms, brushes, or similar tools should not be used in an operational cleanroom, as they will cause gross particle generation. The bristles themselves are very large fibres that are also a contaminant. E.5.11 Receptacles for rubbish and recycling Used materials, by-products and other waste generated inside the cleanroom should be removed as soon as possible. A means for the collection, containment and storage of wastes should be provided to protect the cleanroom from these contamination sources while waiting for removal. Removal procedures are discussed in F.4.10. The following criteria should be considered when selecting receptacles for collection of these materials: a) nature of the materials to be discarded or recycled; b) safety requirements; c) environmental hazards; d) lining materials and how they will be installed; e) floor space available; f) size required, based on frequency of collection; g) material of construction; h) cleanroom compatibility. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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E.5.12 Cleanroom mats and sticky flooring Cleanroom mats and sticky flooring can be used as a barrier to help control foot-borne contamination from entering the cleanroom. The size (particularly the length) and location of the mats/flooring are the major factors governing the effectiveness for the removal of foot-borne contamination. Two major varieties of available mats/flooring are: a) Disposable — Multiple layers of adhesive, plastic film with the sticky surface facing up. Layers are removed and discarded as they get dirty. b) Reusable — Resilient polymeric mat with a naturally sticky surface, to be cleaned when it becomes dirty. E.5.13 Clean containers and packaging Clean containers can be used for transporting or isolating sensitive materials and products to and from the cleanroom while waiting to be used or processed. Surface cleanliness and isolation characteristics should be consistent with the intended use of the enclosed materials. Entry and exit procedures as stated in E.4 should be followed. Frequent cleaning may be necessary to avoid contamination buildup during use. Special cleaning and verification of cleanliness may be required before reuse. Materials that may be used to protect or package finished products made in the cleanroom should be clean and compatible with the cleanroom. Selection should be based on particle generation, microbial contamination, electrostatic properties, outgassing and other concerns. Tapes that are used within the cleanroom should have adhesives that leave minimal residues when removed. E.5.14 Hand tools, boxes and maintenance equipment Hand tools should be compatible with the cleanroom classification, products, stationary equipment and processes with which they will come into contact. They should be kept clean and free from contamination of all kinds. Boxes or cases that contain tools and other repair or diagnostic equipment are often overlooked sources of contamination. They should be made of stainless steel or synthetic materials that resist or protect against the generation or transfer of contamination. Any use of moulded inserts or dividers that can generate contamination such as open-cell foam, vinyl-covered wood or pressboard (wood-chip board) should be avoided. Boxes should be thoroughly cleaned on a regular and scheduled basis (with tools and instruments removed) to ensure cleanliness. Tools and instruments should be cleaned before being replaced inside the toolbox or case. Toolboxes and cases should remain inside the cleanroom whenever possible. If removed from the environment, toolboxes and cases should never be opened outside the cleanroom. Thorough external cleaning should be required before being allowed back inside the cleanroom. Carts and trolleys routinely used for transferring maintenance and other supplies into and out of the cleanroom must be thoroughly cleaned before re-entry. NOTE Initial and routine sterilization or disinfection of the above items may be required when used in the biocleanroom. E.5.15 Safety equipment Safety goods and equipment used in the cleanroom such as chemical gloves, aprons, face and arm shields, self-contained breathing apparatus, chemical absorbing pads and fire extinguishers should be selected for their intended safety requirements as well as compatibility with the intended cleanroom. E.5.16 Written documentation Contamination from documents, within the cleanroom, should be controlled. Methods for documentation will depend largely on the use and classification of the cleanroom. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Paper and paper products will contaminate the cleanroom. All documents should be printed on lint-free, cleanroom-compatible media or thermally laminated between plastic films. Information on the selection of such substrates is given in other sources. [28] Use of such media in the form of labels, log sheets, equipment repair manuals, reports and notebooks should be controlled and kept to a minimum. Label adhesives should leave minimal residues when removed from surfaces. Writing instruments can become sources of contamination to the cleanroom, products or processes. Pencils, rubber erasers and felt-tipped and retractable pens should be avoided. Pens should be of the non-retractable, ballpoint style with inks that are permanent and compatible. E.5.17 Electronic documentation The use of computers for work in progress will eliminate the need for many sources of contamination such as log books, log sheets, process documentation and others. Installation and use of computers and peripherals should be compatible with the classification of and intended location inside the cleanroom. Computers often employ internal cooling fans. Consideration should be given to how the exhaust air may affect the cleanroom and critical surfaces surrounding the computer. Methods may need to be devised to duct such exhaust directly to air returns or through portable filtration units, depending on cleanliness requirements. Keyboards have recesses around the pushbuttons that may trap and release particles. Use of flexible continuous films or covers placed over the keyboard will facilitate cleaning and reduce contamination. Printers interfaced with such computers should be appropriately contained or isolated and exhausted in a similar manner. Printer maintenance should be performed carefully to avoid dispersal of residual contamination generated by the printing operation. E.5.18 Other materials Other materials, including those directly used in the production process, are taken into the cleanroom. They should exhibit the lowest possible contamination properties for the application intended and the classification of the cleanroom. They should enter and be controlled in an appropriate manner as described above and be compatible with products and processes. E.6 Storage Materials can become contaminated or ineffective if improperly stored while waiting to be used. Proper storage and controlled storage methods are critical to preserve their effectiveness. They should be stored in an environment that protects them from degradation and contamination. If not properly stored, the accumulation of unused materials in the cleanroom presents a risk of contamination. Certain classes and types of waste materials are stored in the cleanroom until specified limitations are reached. Often, these limits are regulated by agencies or by recycling programmes set up for the cleanroom. The use of specialized containers may also be required. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Annex F (informative)

Cleanroom cleaning F.1 Overview Cleanrooms are designed to be as free from contamination as possible. Facility and maintenance operations, manufacturing processes, the presence and activity of personnel and other factors may cause contamination to be generated and dispersed on surfaces in the cleanroom. Therefore, all surfaces should be cleaned frequently enough to prevent this from becoming a risk to the manufacturing process. Procedures should be specified to ensure that thorough and complete cleaning operations are performed in a manner that is consistent with recommended cleanroom practices for the facility. When feasible, cleaning should be avoided during manufacturing operations. If this is not possible, special cleaning procedures should be devised to minimize risks. Information is available in a number of documents that will assist in effective cleaning of a cleanroom [29] [31] [32]. NOTE Some processes generate contamination as a by-product. It is better to identify and attempt to contain contamination from such operations than to rely on cleaning to control the contamination. F.2 Surface classification F.2.1 General The cleanliness of areas and surfaces should be classified and designated based upon how they may affect the products and processes performed in the cleanroom. Effective application of this classification will be useful in developing the proper cleaning strategy for the cleanroom. F.2.2 Critical surfaces Surfaces classified as critical are located at and around the point of manufacture or production where contamination can gain direct access to the product or process. These surfaces should be kept the cleanest. Separative devices, including unidirectional airflow equipment, clean benches or workstations, usually help control the cleanliness of these surfaces. F.2.3 General cleanroom surfaces All surfaces within the cleanroom that are not at the point of production or localized by unidirectional airflow are considered “general”. They should be cleaned on a regular basis to prevent transfer of contamination onto critical surfaces. F.2.4 Surfaces of changing rooms and transfer areas Surfaces of changing rooms and transfer areas can become highly contaminated due to the high level of activity. Frequent cleaning is necessary to minimize the level of contamination and to reduce the transfer of contamination into the cleanroom. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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F.3 Basic cleaning F.3.1 General Maintaining the cleanliness of a cleanroom is a meticulous set of tasks. Cleaning levels should be defined and basic methods for attaining those levels should be developed. Approved methods can then be applied to every surface within the cleanroom to achieve the desired result. [10] [29] [30] [31] [32]. F.3.2 Basic cleaning categories The act of cleaning can be divided into three different categories depending on the current state and desired cleanliness of the surface once cleaning is completed. These are gross, intermediate and precision, and are described as follows:  Gross cleaning involves the removal of large particles of contamination usually greater than 50 µm in diameter. Contamination of this size is usually found on floors and is typical of the type carried into changing and transfer areas. Broken or spilled materials resulting from the production operation or process are additional sources of contamination that end up on work surfaces and floors. Construction and equipment maintenance activities also can often generate gross particle contamination.  Intermediate cleaning involves the removal of smaller particles of contamination, typically ranging from 10 µm to 50 µm in diameter. Performed on general cleanroom surfaces, intermediate cleaning is usually associated with walls, benches and clean hallways. This size of contamination remains after gross cleaning methods are used. Intermediate cleaning provides the next level of cleanliness.  Precision cleaning is needed to remove remaining particulate contamination that is generally less than 10 µm in diameter. Precision cleaning is generally employed on or near critical surfaces where product is stored and processed. F.3.3 Vacuum cleaning Vacuum cleaning can be used in gross and intermediate cleaning operations as a basic first step to cleaning both general and critical areas. Vacuum cleaning is a prerequisite, not an alternative, to mopping or wet wiping. Vacuum cleaning is effective in removing larger particles and other debris such as glass fragments. Vacuum cleaning should be performed in deliberate, unidirectional strokes to minimize air turbulence at the floor level and at operator height. The use of HEPA/ULPA vacuum cleaners or in-house central vacuum systems is employed in vacuum cleaning. Systems that can accommodate wet materials are helpful for removing excess water and suspended particles during and after the mopping process. Vacuum cleaning can also be useful in helping to speed the drying process once mopping is completed. F.3.4 Wet cleaning Wet cleaning methods where liquid is applied to a surface and removed through wiping or vacuuming methods can be employed in all stages of cleaning. Methods for wet cleaning include:  Scrubbing is a gross cleaning method that employs machine or manual methods to remove stains or heavily soiled areas. Care should be taken to control any contamination that may be generated by the equipment or materials used in scrubbing. Mopping or wet vacuuming procedures follow scrubbing.  Mopping is an effective method in gross or intermediate cleaning for removing contamination. Mopping can also be used for removing residues from spilled liquids left after wet vacuuming is completed. Wet wipers may be used in small or localized areas. Mops are used for floors and other large areas. The mop bucket should be filled with clean-filtered de-ionized or distilled water and changed frequently to avoid recontamination. The more critical the surface, the more frequently the water should be changed. Water coloration indicates the need for the bucket to be emptied, cleaned and refilled for use in the gross Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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cleaning mode. Intermediate and critical areas should show little or no coloration throughout specified use, so cleaning procedures for these areas should define the allowable surface area to be cleaned before changing the water. Two (or multiple) bucket systems can be used to reduce the frequency of rinse water changes. Non-ionic detergents or surfactants can be added if necessary. Mops should be well squeezed to avoid puddles. A damp mop will produce a damp surface that will dry more quickly. A systematic method, using overlapping strokes should be employed to ensure complete cleaning of floor surfaces. Frequent rinsing and turning of mop surfaces help to avoid recontamination of previously cleaned sections of the floor. Mop heads should be rinsed frequently to avoid recontamination of the mop head. Specialty mops are also available for removing intermediate-sized contamination from walls, and floors (see E.5.6). F.3.5 Damp cleaning Wiping techniques are used in most phases of cleaning. Wiping produces results that support intermediate and precision cleanliness for general and critical surfaces. The chosen wiper should be dampened with the appropriate cleaning solution. The solution is dependent upon the type of contaminant being removed. Wiping should always be done in unidirectional, overlapping strokes, proceeding from most critical to least critical areas, following the direction of unidirectional airflow. As wiping proceeds, wipers should be folded to provide an unused surface area. The wiper should be replaced as frequently as needed to avoid transferring contaminants to other parts of the cleanroom surface. F.4 Cleaning specific surfaces F.4.1 Identifying surfaces to be cleaned All surfaces within the cleanroom can become contaminated and should be cleaned at some identified interval. It is important that all surfaces be identified according to how critical the cleanliness of the surface is to the product or process performed in the cleanroom. Cleaning techniques can then be developed and specified to ensure that the required level of cleanliness is attained. F.4.2 Floors and subfloors Gross contamination can be removed first by vacuum cleaning e.g. glass or product fragments. Areas with stubborn stains should then be identified and addressed with predetermined scrubbing procedures. The floor should be wet or damp mopped according to predetermined procedures. Water or cleaning solutions should be changed frequently enough to minimize the spread of dissolved or suspended contamination as the cleaning process continues. Larger floor areas should be divided into manageable segments so that work can proceed in an orderly manner. Cleaning should begin in critical areas and proceed through general areas, but certain cleanroom applications may require a different routine. Repeating the mopping procedure will produce cleaner surfaces if greater cleanliness levels are required. During operational hours, it may be necessary to cordon off the area and redirect traffic flow to avoid dangerous falls by unwary personnel. Damp mopping or wet vacuuming after mopping will speed the drying process. Wet washer/scrubber systems, followed by wet vacuum cleaning, can be used to remove stubborn stains and floor stains. These systems are described in E.5.8 and should be thoroughly cleaned before and after each use. F.4.3 Walls, doors, return grilles, windows and vertical surfaces In unidirectional flow cleanrooms, surfaces upstream from product exposure should never be cleaned in the operational state. Upstream surfaces should only be cleaned in the at-rest state or after products have been removed from the area or covered. Contamination should be removed using wiping methods or special purpose or roll mops. Choice of method should be determined based on state of cleanliness desired and configuration of the area being cleaned. In non-unidirectional flow cleanrooms, surfaces should not be cleaned during normal operations. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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F.4.4 Ceilings, diffusers and lamp fixtures Ceilings and other fixtures upstream or close to work areas should not be cleaned in the operational state but should wait for at-rest conditions. Diffuser and ceiling grids should be carefully wiped using damp cleaning techniques. Some diffusers may require removal for washing or replacement. Lamp fixtures should be thoroughly wiped whenever bulbs are changed. F.4.5 Tables and other critical horizontal surfaces Tables and other critical horizontal surfaces should be cleaned using appropriate wiping techniques described above. Acceptable cleaning solutions may be used to aid in contamination removal. Damp wipers can be used to remove contamination, working in unidirectional strokes from most to least critical areas. F.4.6 Cleanroom chairs, furniture and ladders Wipe chairs, furniture and ladder surfaces from top to bottom. Include cushions, supports, and wheels if equipped. F.4.7 Stationary equipment Surfaces of stationary equipment should be cleaned according to the risk presented to the cleanroom and products. It is important to note that fluid piping, electrical wires and connections often supply stationary equipment. Extreme care must be taken to avoid damaging or disconnecting piping or wires during the cleaning operation. Stationary equipment often contains surfaces that are critical to the product or process cleanliness. These surfaces should be classified so that an appropriate cleaning programme can be established for each type of surface. A careful assessment of the following surfaces should be made to assure effective cleaning. a) Exterior surfaces of stationary equipment are common to the cleanroom environment. These surfaces should be cleaned according to procedures determined appropriate for walls, horizontal and vertical surfaces. b) Interior surfaces are made up of the inner walls of the stationary equipment and the machinery contained within the equipment. Inner walls often surround the critical product or process areas. Cleaning of these surfaces often may not proceed until products or process components are removed from the equipment. These surfaces may also become contaminated with product or process residues, requiring special safety considerations prior to cleaning. Machinery contained within stationary equipment should be maintained and cleaned on a periodic basis and in accordance with manufacturers specifications and as described in D.5. c) Critical surfaces of stationary equipment are the closest to products or processes that are enclosed or surrounded by the equipment and cannot be done in the presence of product or process. Procedures and schedules for cleaning should be developed and specified and carried out in accordance with product and process cleanliness requirements. F.4.8 Carts and trolleys Carts and trolleys should be vacuumed or wiped down, or both, using wipers and starting from the top and working downward using acceptable cleaning solutions in an appropriate transfer area or other non-critical area. Special care should be taken to assure that the rolling surfaces of the wheels are free from debris that may be deposited on the cleanroom floor. Rolling carts or trolleys over sticky mats can help in the removal of such debris from the wheels. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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F.4.9 Hazardous processing surfaces Procedures should be developed to neutralize existing hazards before beginning normal cleanroom cleaning procedures. Use the appropriate cleaning technique for the surface involved and described in F.3.1 to F.3.5. F.4.10 Cross-over benches, supply and cleanroom clothing supply cabinets, lockers and other compartmented surfaces Vacuum cleaning followed by wiping will effectively remove contamination from exposed surfaces. Compartments should be periodically emptied so that the interiors can be cleaned. F.4.11 Rubbish bins and containers Rubbish bins and containers can be lined with plastic bags to facilitate removal of refuse and protect container surfaces. Rubbish should be removed before it collects in excess. Plastic bags or liners should never be removed from bins in the vicinity of critical areas. All bins should be removed to general, non-critical areas before any rubbish is removed. This can be done as required or at the end of each shift. They should be emptied, cleaned and re-lined, if required, before being returned to service. F.4.12 Cleanroom mats and sticky flooring Cleanroom mats and sticky flooring should be cleaned or maintained on a regular basis during the normal workday. Cleanroom mats and sticky flooring should be serviced according to the manufacturer’s instructions as frequently as needed. Mats with renewable surfaces should be cleaned frequently. After wet mopping, a rubber squeegee is used to pull contamination and water to the edge to be mopped dry. A wet vacuum with a squeegee head can also be used for this purpose. Mats with removable, sticky surfaces are cleaned by slowly peeling each of the four corners and rolling the film towards the middle of the mat until the layer is removed. F.5 Surface treatment F.5.1 General Specific cleanroom applications require that certain surface treatments or finishes are applied to cleanroom surfaces, to provide characteristics that normally would not exist. These treatments may protect the products being produced in the cleanroom, but should be carefully considered. The use of surface treatments and finishes, after cleaning, should be avoided if at all possible. These treatments deteriorate with time and will compromise the cleanliness of the cleanroom. In addition, these treatments can pose the risk of process or product contamination if not used or maintained properly. Surfaces that receive these treatments should be inspected or tested on a periodic basis to ensure they do not compromise the cleanroom. Steps can then be taken to remedy the situation. F.5.2 Anti-static treatment Anti-static materials can be applied to surfaces to minimize static charge buildup. Treating surfaces with anti- static agents should be done carefully. Improper use will result in non-uniform, anti-static characteristics and residues that can become a source of contamination. The coating should be thick enough to be effective but thin enough to avoid flaking and generation of contamination. Anti-static surface characteristics can often be achieved simply by changing the humidity of the air supplied to the cleanroom. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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F.5.3 Disinfection Thorough cleaning programmes help to control micro-organisms. However, certain industries and regulatory agencies may require disinfection procedures in addition to normal cleaning procedures. The effectiveness of the disinfectants and the methods used for disinfection should be determined in each cleanroom. In general, disinfectant efficacy is a function of the type of disinfectant, the concentration of the disinfectant, the temperature of the solution and its contact time on the surface being disinfected. Some disinfectants can damage cleanroom surfaces (e.g. chlorine-based compounds on stainless steel) if they are not properly removed, and may be toxic if they are deposited on products. Furthermore, disinfectants may be toxic not only when in direct contact with the product, but also when a residue remains on surfaces. Therefore, it may be appropriate to remove such residues by properly rinsing the surfaces. Disinfectants can have harmful effects on personnel if used improperly. F.6 Cleaning personnel A specific training program should be provided for any personnel performing the cleaning operation. Specific personnel should be designated for each part of the cleaning programme. It is quite common to assign cleanroom cleaning to specialized cleaning personnel. Operators with proper training are often assigned to clean the work surfaces. F.7 Cleaning programme F.7.1 Preparing a cleaning programme The classification of different kinds of cleanroom surfaces and the rate at which they become contaminated should be understood when setting up a cleaning programme. Schedules should be specified to ensure cleaning is performed frequently enough to maintain the required cleanliness of the cleanroom. Testing and evaluation of the surface contamination will assist in drawing up schedules. The process and product requirements within the cleanroom should determine which cleaning tasks need to be accomplished on a daily, weekly or other periodic basis. [29] The following steps should be followed in preparing a cleaning programme. a) Classify all surfaces into critical, general or other surfaces. b) Determine the best cleaning and surface treatment method for achieving the desired cleanliness level. c) Determine the cleaning frequency required to maintain the desired cleanliness levels for each surface type. d) Determine which cleaning operations can be accomplished during normal operating hours. e) Prepare the cleaning schedules. f) Decide which part of the cleaning schedule operators will execute and which part cleaning staff will execute. g) Choose the correct materials, machines, cleaning solutions and surface treatments for the specified methods. h) Train all personnel for the expected level of involvement in the cleaning programme. i) Provide adequate storage facilities for the required cleaning materials. j) Decide how to monitor the cleaning results and react to discrepancies. k) Organize all documents and schedules so that they can be reviewed and managed effectively. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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F.7.2 Scheduling the cleaning programme Most cleaning operations should be performed on a regularly scheduled and frequent basis. Other cleaning operations are performed on a scheduled basis but infrequently. Some cleaning operations must be done in reaction to events that create contamination and are not subject to normal scheduling. The frequencies, listed below, can be used as guidelines but should be adjusted to the needs of the cleanroom as based on a risk assessment and cleaning evaluation. F.7.3 Regular cleaning Regular cleaning includes all tasks that are carried out frequently enough to reduce the risk of contamination from being transferred to critical surfaces. Tasks associated with regular cleaning of the cleanroom may be performed several times per day, once per day, or every several days depending on the risk assessment. Many tasks may be allowed during working hours, such as trash removal, vacuuming, mopping floors, and wiping surfaces in changing areas, transfer areas and common areas such as hallways. Each room within the cleanroom may need a special written cleaning programme depending on criticality of cleanliness to product or process concerns. Changing areas and transfer areas should be cleaned at least once per day. These areas can harbour high contamination levels, due to the high level of personnel activity. Therefore, cleaning is required more frequently than in manufacturing cleanrooms to control the cleanliness level and reduce the opportunity for contamination transfer. Regular cleaning will enhance the level of cleanliness within the general cleanroom areas. Thorough vacuum cleaning and mopping procedures described in F.3.3 and F.3.4 should be implemented. Cleanroom mats and sticky flooring should be serviced (described in F.4.12) but with greater frequency to prevent the migration of contamination into the cleanroom. F.7.4 Periodic cleaning Surfaces not cleaned on a regular basis should be cleaned periodically. Special precautions may need to be taken to ensure product integrity during cleaning procedures. Many surfaces should be cleaned on a weekly basis (i.e. at least once during a seven-day period). Product may need to be covered or removed from areas where weekly service is performed. Surfaces that present less of a risk can be scheduled for less frequent cleaning. This type of less frequent cleaning should be performed once per month or extended time interval. Schedules should reflect these less frequent intervals. Arrangements should also be made to thoroughly clean the entire cleanroom facility, from top-to-bottom, on a scheduled basis. Thorough cleaning should include storage areas, service areas, pipes and fittings. Thorough cleaning is often best accomplished during extended facility shutdowns or during weekends, holidays or other planned facility shutdowns. Continuously operating cleanrooms are only shut down sporadically and may only have certain times when thorough cleaning can be accomplished. Intensive cleaning efforts should be taken at these times to accomplish the task. F.7.5 Cleaning during and after construction or maintenance Effective cleaning during cleanroom construction is essential to control and eliminate contamination sources that might later affect the operational cleanroom. Annex D provides guidance for maintenance activities. A sample 10-stage cleaning schedule in F.9 can be used to aid in planning, executing, and documenting efforts. F.7.6 Cleaning during emergency situations Procedures should be instituted to ensure that work-in-progress, the process and the cleanroom environment are not compromised in the case of a gross contamination event. Special tools and materials should be readily available to neutralize or control any hazardous situations that may arise. Work should be suspended in the area deemed at risk until acceptable levels of cleanliness are attained. Events that may trigger special cleaning include: Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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a) environmental incident (e.g. utility failure, spill, major equipment failure, broken product, biological hazard, etc.); b) failure of routine cleaning procedures resulting in contamination rising to unacceptable levels; c) monitoring that reveals the occurrence of unacceptable contamination of the facility. F.8 Monitoring cleaning effectiveness and testing F.8.1 Particle contamination Cleanroom equipment, apparatus or surfaces may require cleanliness testing and monitoring after cleaning. Users are responsible for selecting appropriate cleanliness verification methods. An acceptable degree of cleanliness should be determined for each element or characteristic that will affect the products or processes in the cleanroom. The user should specify limits for tests performed. It is recommended that, when possible, limits be determined from actual measurements, using the test methods. Routine surface contamination checks should be defined and carried out to ensure that the specified levels are being maintained [24] [31] [34]. Visual inspection techniques can be used to determine surface cleanliness. Visual-clean surfaces demonstrate an absence of contamination that can be seen without magnification. Visual inspection may be accomplished with or without the aid of angled, high-intensity white light or ultraviolet light sources. Wiper- clean surfaces can be demonstrated by passing a clean wiper over a clean surface. This inspection aid detects visual contamination that may adhere to the wiper surface indicating further cleaning is needed. Coloured wipers are available from some suppliers and may be helpful in detecting some forms of contamination. Other methods that may be considered include: a) tape lift method [33]; b) surface particle detector method [30]. NOTE Additional methods for measuring surface cleanliness in critical areas are discussed in other sources [10] [30] [31] [34] [35] [36]. F.8.2 Microbiological contamination A variety of methods and sampling schemes exists for detecting microbiological contamination in the cleanroom. These are described in other sources. [26] [32] The following methods are the most common: a) contact plates (for flat surfaces); b) surface swabbing (for uneven surfaces). F.9 Construction-related cleaning programme Depending on the user requirements, the following 10-stage programme can be used effectively to schedule, assign and document cleaning procedures that are needed during different phases of construction operations (see also ISO 14644-4, Annex E). Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Table F.1 — Stages of construction-related cleaning programme Stage Purpose Responsible party Method Standard Stage 1 — Clean during demolition or preliminary construction such as framing for wall installation. Preventing unnecessary dust concentration in places that will be difficult to reach during later construction. Contractor. If the construction contractor has no relevant experience in cleanroom cleaning, it is advisable to hire a professional cleaning contractor specializing in cleanroom cleaning. Vacuum clean upon completion. Visual-clean. Stage 2 — Clean during utility installation. Removing local contaminants caused by installing electricity, gas, water, etc. Installation engineer. Vacuum clean; wipe- down piping and fixtures with moistened wipers upon completion. The use of vacuum cleaning and/or other cleaning materials is necessary. Visual-clean. Stage 3 — Clean during early construction. Cleaning all visible contamination from ceilings, walls, floors, (filter mountings), etc. after completion of construction and installation activities. Cleaning contractor. Vacuum clean; wipe- down piping and fixtures with moistened wipers. Application of protective floor sealants is generally a particle generating activity. If this is necessary, it should be applied at this time. Visual-clean. Stage 4 — Prepare for air conditioning ductwork installation.

Cleaning any dust from ductwork sections before installing using a vacuum cleaner and wipers. Meanwhile, a positive pressure should be introduced to the cleanroom. Installation engineer and cleaning contractor. Vacuum clean; wipe down with moistened wipers. Wiper-clean. Stage 5 — Clean before mounting all air filters into the system. Removing deposited or settled dust, or both, from ceilings, walls, and floors. Cleaning contractor. Wipe down with moistened wipers. Wiper-clean. Stage 6 — Mount the (HEPA/ULPA) filters into the air systems Removing possible contamination caused by the mounting operation. Cleanroom HVAC filter engineer/ technician. Clean all surface edges on all sides. Wiper-clean. Stage 7 — Adjust the air conditioning equipment. Removing suspended dust from the airflow and creating over- pressure installation, including the filters. Cleanroom HVAC filter engineer/ technician. Air conditioning air flushing operation. Wiper-clean. Stage 8 — Upgrade the room into prescribed classification.

Removing all deposited and clinging dust from every surface (in order: ceilings, walls, equipment, floors). A professional cleanroom cleaning by personnel specially instructed on regulations, routing and behaviour. Wipe down with moistened wipers. Wiper-clean.

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Table F.1 (continued) Stage Purpose Responsible party Method Standard Stage 9 — Approve installation. Verifying the cleanroom to the prescribed design specifications. Customer acceptance. Installation engineer and certification engineer. Monitor airborne and surface particles, air velocities, temperature and humidity. Wiper-clean. Results should conform to agreed design criteria. Stage 10 — Clean daily and periodically Maintaining the cleanroom in long-term compliance with designed classification. Microbiological cleaning and testing begins in biocleanrooms. Cleanroom manager/cleaning contractor. Listed in F.1 to F.8. A tailor-made cleaning programme for the cleanroom, accounting for the specific demands of the production process and the customer. Routine testing of critical operation parameters. NOTE 1 During Stages 4 to 10, all high-efficiency and ultra-high-purity components, such as filters, ducts, etc., should arrive on site protected by plastic or foil covers on both ends. Covers should only be removed when ready for use. NOTE 2 During Stages 6 to 10, all activities should be done wearing prescribed cleanroom clothing.

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Bibliography [1] PIERSON, M.D. and CORLETT, D.A. Jr.: HACCP principles and applications. New York: Van Nostrand Rheinhold, 1992 [2] IEC 60812:1985, Analysis techniques for system reliability — Procedure for failure mode and effects analysis (FMEA). Geneva, Switzerland: Commission Electrotechnique Internationale/International Electrotechnical Commission [3] PALADY P.: FMEA, failure modes and effect analysis. West Palm Beach, Florida: PT Publications, Inc., 1995 [4] IEC 61025:1990, Fault tree analysis (FTA). Geneva, Switzerland: Commission Electrotechnique Internationale / International Electrotechnical Commission [5] WHYTE, W.: Cleanroom Technology — Fundamentals of Design, Testing and Operation. West Sussex: J. Wiley and Sons, 2001 [6] IEST-RP-CC027.1:1999, Personnel practices and procedures in cleanrooms and controlled environments. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [7] AS 2013.1:1989, Cleanroom garments: product requirements. North Sidney: Standards Association of Australia [8] IEST-RP-CC003.3:2003, Garment system considerations in cleanrooms and other controlled environments. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [9] VCCN-RL-6.2:1996, Cleanroom garments: Recommended practices for choice, logistics and use of cleanroom garments. Amersfoort: Dutch Society of Contamination Control (Dutch language only) [10] VDI 2083 part 4:1996, Cleanroom technology — Surface cleanliness. Berlin: Beuth Verlag GmbH [11] ISO 9237:1995, Textiles — Determination of the permeability of fabrics to air [12] ASTM-D737-96:1996, Test method for air permeability of textile fabrics. West Conshohocken, Pennsylvania: American Society for Testing and Materials [13] JIS B 9923:1997, Methods for sizing and counting particle contaminants in and on clean room garments. Tokyo: Japanese Industrial Standards [14] ASTM F51-68:1989, Standard methods for sizing and counting particulate contamination in non- cleanroom garments. West Conshohocken, Pennsylvania: American Society for Testing and Materials [15] EN 1149-1:1994, Protective clothing — Electrostatic properties — Part 1: Surface resistivity (test methods and requirements) [16] IEST-RP-CC022.1:1992, Electrostatic charge in cleanrooms and other controlled environments. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [17] VCCN-RL-5:1996, Thermal comfort: Recommended practices for thermal comfort requirements for people working in cleanrooms. Amersfoort: Dutch Society of Contamination Control. (Dutch language only) [18] ISO 11092:1993, Textiles — Physiological effects — Measurement of thermal and water-vapour resistance under steady-state conditions (sweating guarded-hotplate test) [19] BS 7209:1990, Water vapour permeable apparel fabrics. London: British Standards Institution Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:23:44 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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[20] ISO 7730:1994, Moderate thermal environments — Determination of the PMV and PPD indices and specification of the conditions for thermal comfort [21] AS 2013.2:1989, Cleanroom garments: Processing and use. North Sidney: Standards Association of Australia [22] IEST-RP-CC005.3:2003, Gloves and finger cots used in cleanrooms and other controlled environments. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [23] VCCN-RL-6.3:1996, Rules for behaviour in the cleanroom: Recommended practices for personnel behavior in cleanrooms. Amersfoort: Dutch Society of Contamination Control (Dutch language only) [24] IEST-RP-CC026.1:1995, Cleanroom operations. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [25] JIS B 9926:1991, Test methods for dust generation from moving mechanisms. Tokyo: Japanese Industrial Standards [26] IEST-RP-CC023.1:1993, Microorganisms in cleanrooms. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [27] IEST-RP-CC004.2:1992, Evaluating wiping materials used in cleanrooms and other controlled environments. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [28] IEST-RP-CC020.2:1996, Substrates and forms for documentation in cleanrooms. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [29] JACA Number 27:1992, Guidance for cleaning of clean room facilities. Tokyo: Japan Air Cleaning Association (Japanese language only) [30] IEST-RP-CC018.3:2002, Cleanroom housekeeping — Operating and monitoring procedures. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [31] VCCN-RL-4:1996, Surface cleanliness: Recommended practices for microbiological and particle surface cleanliness, and cleaning in cleanrooms. Amersfoort: Dutch Society of Contamination Control (Dutch language only) [32] JACA Number 32:1996, Guideline for cleaning of biological clean room facilities. Tokyo: Japan Air Cleaning Association (Japanese language only) [33] ASTM E 1216-87:1987, Practice for sampling for surface particulate contamination by tape lift. West Conshohocken, Pennsylvania: American Society for Testing and Materials [34] JACA Number 22:1988, A guideline of measuring methods for surface particle contamination. Tokyo: Japan Air Cleaning Association (Japanese language only) [35] JACA Number 30:1993, The report of the surface contamination control technology survey committee. Tokyo: Japan Air Cleaning Association (Japanese language only) [36] IEST-STD-CC1246D:2002, Product Cleanliness Levels and Contamination Control Program. Rolling Meadows, Illinois: Institute of Environmental Sciences and Technology [37] VDI 2083 part 6:1996, Cleanroom technology — Personnel at the clean work place. Berlin: Beuth Verlag GmbH [38] JACA Number 14C:1992, Guidance for operation of clean rooms. Tokyo: Japan Air Cleaning Association (Japanese language only)

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Source: ISO 14644-7.pdf Pages: 60

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Reference number ISO 14644-7:2004(E) © ISO 2004

INTERNATIONAL STANDARD ISO 14644-7 First edition 2004-10-01 Cleanrooms and associated controlled environments — Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini- environments) Salles propres et environnements maîtrisés apparentés — Partie 7: Dispositifs séparatifs (postes à air propre, boîtes à gants, isolateurs et mini-environnements)

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--- PAGE 2 --- ISO 14644-7:2004(E) PDF disclaimer This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat accepts no liability in this area. Adobe is a trademark of Adobe Systems Incorporated. Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.

© ISO 2004 All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISO's member body in the country of the requester. ISO copyright office Case postale 56 • CH-1211 Geneva 20 Tel. + 41 22 749 01 11 Fax + 41 22 749 09 47 E-mail copyright@iso.org Web www.iso.org Published in Switzerland

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--- PAGE 3 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved iii

Contents Page Foreword............................................................................................................................................................ iv Introduction ........................................................................................................................................................ v Scope...................................................................................................................................................... 1 Normative references ........................................................................................................................... 1 Terms and definitions........................................................................................................................... 2 Requirements ........................................................................................................................................ 3 Design and construction...................................................................................................................... 5 Access devices ..................................................................................................................................... 6 6.1 Use.......................................................................................................................................................... 6 6.2 Manual operation .................................................................................................................................. 6 6.3 Robotic handling................................................................................................................................... 7 Transfer devices.................................................................................................................................... 7 7.1 Use.......................................................................................................................................................... 7 7.2 Selection ................................................................................................................................................ 7 7.3 Fail-safe design..................................................................................................................................... 7 Siting and installing.............................................................................................................................. 7 Testing and approval............................................................................................................................ 8 9.1 General................................................................................................................................................... 8 9.2 Glove breach test.................................................................................................................................. 8 9.3 Operating differential pressure ........................................................................................................... 8 9.4 Leak testing ........................................................................................................................................... 8 9.5 Periodic testing ..................................................................................................................................... 9 Annex A (informative) Separation continuum concept ................................................................................ 10 Annex B (informative) Air-handling systems and gas systems................................................................... 13 Annex C (informative) Access devices........................................................................................................... 16 Annex D (informative) Examples of transfer devices ................................................................................... 22 Annex E (informative) Leak testing................................................................................................................. 31 Annex F (informative) Parjo leak test method ............................................................................................... 40 Bibliography ..................................................................................................................................................... 51

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--- PAGE 4 --- ISO 14644-7:2004(E) iv © ISO 2004 – All rights reserved

Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2. The main task of technical committees is to prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 14644-7 was prepared by Technical Committee ISO/TC 209, Cleanrooms and associated controlled environments. ISO 14644 consists of the following parts, under the general title Cleanrooms and associated controlled environments:  Part 1: Classification of air cleanliness  Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1  Part 4: Design, construction and start-up  Part 5: Operations  Part 6: Vocabulary  Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) The following parts are under preparation:  Part 3: Test methods  Part 8: Classification of airborne molecular contamination

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--- PAGE 5 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved v

Introduction In the spirit of the generic requirements of an International Standard, the term “separative devices” was developed by Technical Committee ISO/TC 209 to encompass the wide continuum of configurations from open unrestricted air overspill to wholly contained systems. Common terms-of-trade, such as clean air hoods, gloveboxes, isolators and mini-environments, have different meanings depending on the specific industry. Difficulties experienced in the manufacture and handling of certain products or materials have driven the development of separative devices. These difficulties include product sensitivity to particles, chemicals, gases or microorganisms; operator sensitivity to the process materials or byproducts; and both product and operator sensitivity. Separative devices provide assured protection in varying levels by utilising physical or dynamic barriers, or both, to create separation between operation and operator. Certain processes may require special atmospheres to prevent degradation or explosions. Some systems may be capable of providing 100 % recirculation of the contained atmosphere to allow inert gas operation or biodecontamination with reactive gases. Usually people do not work directly inside the separative-device environment during production. These separative devices may be movable or fixed, and used for transport, transfer and process. The product or process, or both, are manipulated remotely with access devices either manually, with protection by barrier technology such as wall-integrated personal interface systems (e.g. gloves, gauntlets, half-suits), or mechanically with robotic handling systems. Air cleanliness definitions and test methods covered in ISO 14644-1, 14644-2 and 14644-3 generally apply within separative devices. In applications with biological contamination requirements, ISO 14698-1 and 14698-2 will apply. However, some applications can have special requirements for monitoring because of extreme conditions that may be encountered. These unique conditions are covered in this part of ISO 14644. Transfer devices to move material in and out of separative devices form an important portion of this part of ISO 14644. In addition, material can be moved from one fixed separative device to another in transport containers. Design and construction of cleanrooms, including generic aspects of clean zones, are covered in ISO 14644-4. ISO 14644-4:2001, Figure A.4, illustrates aerodynamic measures or air overspill often used in industry-specific separative devices called clean air hoods and mini-environments. Mini-environments are often used in the electronics industry with transport containers, called boxes or pods, to provide very clean process conditions. The application of barrier technology used in industry-specific separative devices called isolators is shown in ISO 14644-4:2001, Figure A.5. Separative devices, often called gloveboxes, containment enclosures or isolators, are used in the medical products and nuclear industries to provide protection to the operator as well as the process. Isolators may be rigid- or soft-walled depending on the application. The Bibliography contains industry-specific references. However, from a unifying conceptual standpoint, a continuum of separation exists between the operation and the operator, ranging from totally open to totally enclosed systems depending on the application. Similarly, a continuum exists for containment. The concept of separative devices is not limited to one specific industry, as many industries use these technologies for different requirements. In that light, this part of ISO 14644 provides a generic overview of the requirements involved.

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--- PAGE 7 --- INTERNATIONAL STANDARD ISO 14644-7:2004(E)

© ISO 2004 – All rights reserved

Cleanrooms and associated controlled environments — Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) Scope This part of ISO 14644 specifies the minimum requirements for the design, construction, installation, test and approval of separative devices, in those respects where they differ from cleanrooms as described in ISO 14644-4 and 14644-5. The application of this part of ISO 14644 takes into account the following limitations.  User requirements are as agreed by customer and supplier.  Application-specific requirements are not addressed.  Specific processes to be accommodated in the separative-device installation are not specified.  Fire, safety and other regulatory matters are not considered specifically; where appropriate, national and local regulations apply. This part of ISO 14644 is not applicable to full-suits. Normative references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 10648-2:1994, Containment enclosures — Part 2: Classification according to leak tightness and associated checking methods ISO 14644-1:1999, Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness ISO 14644-2:2000, Cleanrooms and associated controlled environments — Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1 ISO 14644-3:—1), Cleanrooms and associated controlled environments — Part 3: Test methods ISO 14644-4:2001, Cleanrooms and associated controlled environments — Part 4: Design, construction and start-up

  1. To be published. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 8 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

ISO 14698-1, Cleanrooms and associated controlled environments — Part 1: Biocontamination control — General principles and methods ISO 14698-2, Cleanrooms and associated controlled environments — Part 2: Biocontamination control — Evaluation and interpretation of biocontamination data Terms and definitions For the purposes of this document, the terms and definitions given in ISO 14644-1, 14644-2, 14644-4 and the following apply. 3.1 access device device for manipulation of processes, tools or products within the separative device 3.2 action level level set by the user in the context of controlled environments, which, when exceeded, requires immediate intervention, including the investigation of cause, and corrective action 3.3 alert level level set by the user in the context of controlled environments, giving early warning of a drift from normal conditions, which, when exceeded, should result in increased attention to the process 3.4 barrier means employed to provide separation 3.5 breach velocity velocity through an aperture sufficient to prevent movement of matter in the direction opposite to the flow 3.6 containment state achieved by separative devices with high degree of separation between operator and operation 3.7 decontamination reduction of unwanted matter to a defined level 3.8 gauntlet one-piece glove covering the full arm-length 3.9 glove 〈of separative devices〉 component of an access device that maintains an effective barrier while enabling the hands of the operator to enter the enclosed volume of an separative device 3.10 glove port attachment site for gloves, sleeves and gauntlets 3.11 glove sleeve system multi-component access device that maintains an effective barrier while enabling replacement of the sleeve piece, connecting cuff piece and glove Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 9 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

3.12 half-suit access device that maintains an effective barrier while enabling the head, trunk and arms of the operator to enter the working space of the separative device 3.13 hourly leak rate Rh ratio of the hourly leakage q of the containment enclosure under normal working conditions (pressure and temperature) to the volume V of the said containment enclosure NOTE It is expressed in reciprocal hours (h–1). [ISO 10648-2:1994] 3.14 leak 〈of separative devices〉 defect revealed by testing under a pressure differential after corrections for atmospheric conditions 3.15 pressure integrity capability to provide a quantifiable pressure leakage rate repeatable under test conditions 3.16 separation descriptor [Aa:Bb] numerical abbreviation summarizing the difference in cleanliness classification between two areas as ensured by a separative device under specified test conditions, where A is the ISO class inside the device; a is the particle size at which A is measured; B is the ISO class outside the device; b is the particle size at which B is measured 3.17 separative device equipment utilizing constructional and dynamic means to create assured levels of separation between the inside and outside of a defined volume NOTE Some industry-specific examples of separative devices are clean air hoods, containment enclosures, gloveboxes, isolators and mini-environments. 3.18 transfer device mechanism to effect movement of material into or out of separative devices while minimizing ingress or egress of unwanted matter Requirements The following information shall be defined, agreed and documented between customer and supplier: a) number, date of publication, and edition of this part of ISO 14644; b) established role of other relevant parties to the project (e.g. consultants, designers, regulatory authorities, service organizations); Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 10 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

c) intended general purpose of equipment, planned operations and any constraint imposed by the operating requirements such as material compatibility, residues and effluents; d) reliability and availability; e) when appropriate, any applicable hazard analysis; NOTE HACCP, HAZOP, FMEA, FTA methods or similar [23] have been found to be suitable; f) required airborne particulate cleanliness class or demands for cleanliness in accordance with ISO 14644-1 and 14644-2. Where appropriate, airborne molecular contamination should be considered [18] [19]; g) specified operational states (e.g. as-built, at-rest, operational) (see ISO 14644-1) and recovery time (e.g. maintenance, cleaning, etc.); h) where appropriate, a specified separation descriptor [25]; i) if devices depend on differential pressure, the differential pressure shall be continuously monitored and alarmed in some applications; j) where appropriate, a specified hourly leak rate (for an example of methodology, see Annex E); k) other operational parameters, including

  1. test points,
  2. alert and action levels to be measured to ensure compliance,

  3. test methods; l) contamination-control concept, including the establishment of installation, operation and performance criteria; m) required methods of measurement, sample locations, control, monitoring and documentation; n) mode of entry or exit of separative devices and related equipment, apparatus, supplies and personnel into the controlled environment required during

  4. installation,

  5. commissioning,

  6. operation,

  7. maintenance; o) layout and configuration of the installation; p) critical dimensions, mass and weight restrictions, including those related to available space; q) process requirements that affect the installation; r) process equipment list with utility requirements; s) maintenance requirements of the installation; t) responsibilities for the preparation, approval, execution, supervision, documentation, statement of criteria, basis of design, construction, testing, training, commissioning and qualification, including performance, witnessing, and reporting of tests; u) identification and assessment of external environmental influences; v) additional information required by the particular application and requirements in Clauses 5, 6, 7 and 8 of this part of ISO 14644; w) compliance with local regulations. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 11 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Design and construction 5.1 Design shall include capability to support qualification and to comply with regulatory requirements. 5.2 Separative-device design shall provide the process, the operator or third party with protection against contamination appropriate to the operation being performed.

5.3 Consideration shall be given to separation means (see Annex A). The separation descriptor, where

applicable, shall be taken into account. The risk of concentrated leaks should be addressed.

5.4 Consideration shall be given to malfunction, procedures and ancillary systems involved with the

separative-device application (see Annex B). 5.5 Consideration shall be given to access devices and transfer devices (see Annexes C and D). 5.6 Separative devices shall be ergonomically designed for easy access to all internal surfaces and work areas, and with respect to the process undertaken.

5.7 Access devices shall be of the minimum size and number consistent with operation, cleaning and

maintenance. (See Clause 6.) 5.8 Consideration shall be given to differential operating pressure, including excursions. 5.9 Hourly leak rate, when applicable, shall be taken into account (see Annex A). The rigidity or flexibility of the separative device shall be taken into account if quantified leak rates are required.

5.10 External influences, such as air flow, vibration and pressure differences, shall be considered to avoid

adverse effects on integrity and function. 5.11 Where appropriate, hazard analysis shall be performed [see 4 e)].

5.12 Provision for cleaning or decontamination, including possible disposal of the device or its components,

shall form part of the design criteria. 5.13 Built-in test facilities and appropriate alarms shall be included. 5.14 Transfer device(s) shall be appropriate to process and routine operation. 5.15 Filtration shall be appropriate for application. 5.16 Volumetric flow rate shall be appropriate for application. 5.17 Exhaust effluents shall undergo treatment where appropriate. 5.18 Whenever possible, items requiring maintenance shall be external to the separative device.

5.19 Materials used in the construction of separative devices, including sealing materials, fans, ventilation

systems, piping and associated fittings, shall be chemically and mechanically compatible with the intended processes, process materials, application and decontamination methods. Protection against corrosion and degradation during prolonged use shall be considered. Heat and fire resistant construction materials shall be considered when appropriate (see Annex B). Where appropriate, materials used shall be checked for thermal characteristics, sorption and out gassing properties. Materials selected for viewing panels shall be tested and proven to remain transparent and resistant to changes that would prevent clear visibility. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Access devices

6.1 Use

Access devices are used to manipulate processes, products or tools within the separative device. Manipulation is achieved by manual operation or robotic handling.

6.2 Manual operation

6.2.1 Devices for manual operation

Operator manual-manipulation devices consist of a) gauntlets, b) glove systems (e.g. sleeve, cuff-ring and glove), c) half-suits and similar devices that allow extended reach, d) remote manipulator. Where full-suits are used, reference should be made to appropriate standards. Where possible, consideration should be given to alternative manipulation devices that minimize the number of holes pierced through the structure of the separative device.

6.2.2 Gauntlets, glove systems, half-suits

6.2.2.1 When using gauntlets, glove systems and half-suits, these types of flexible-membrane access

device systems shall be designed and constructed to allow for glove change without breaching the separative device (see Annex C). These systems are unlikely to maintain molecular containment, therefore alternative systems should be considered for applications requiring molecular containment.

6.2.2.2 Glove ports and glove cuff rings devices shall be designed for ease of change, integrity testing

and security of operation.

6.2.2.3 The following selection criteria shall be considered in choosing gauntlet, glove sleeve and half-

suit system materials that are vital in maintaining separation: a) materials and tools to be handled within the separative device; b) temperature limitations of the glove materials; c) acceptable permeability; d) chemical resistance or mechanical strength, or both; e) sorption and desorption of chemicals; f) known shelf and service lives of glove material; g) differential pressures, including transient excursions (operating and abnormal pressures); h) operations to be performed. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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6.2.3 Remote manipulation

Remote-handling systems consist of mechanical or servo links between an operator’s hands and arms to a mechanical manipulation system within separative devices designed for specific applications.

6.3 Robotic handling

Robotic handling consists of automated systems designed to manipulate materials in a separative device following a process sequence for specific applications. Transfer devices

7.1 Use

Transfer devices shall not diminish the performance of separative devices. In specific applications, transfer devices become critical in maintaining integrity of the device or process. Some transfer devices are used as independent separative devices.

7.2 Selection

Selection of a transfer device shall be based on the level of separation required by the application. The hourly leak rate of the transfer device shall not be greater than the hourly leak rate of the separative device which the transfer device serves. Transfer devices shall minimize the transfer of unwanted matter. Outline diagrams and descriptions of possible types of transfer device are included in Annex D. These diagrams are only illustrative examples of possible configurations.

7.3 Fail-safe design

In the event of power failure, transfer devices that have electrical interlocking mechanisms shall prevent access via the transfer device. Siting and installing 8.1 The cleanroom classification of the room housing the separative device depends on the application, the design, and the operational capability of the separative device. Reference should be made to ISO 14644-4.

8.2 The appropriateness of the following points shall be considered:

a) air classification of the room (ISO 14644-1); b) operational ergonomics; c) maintenance; d) toxicity of materials; e) all process hazards; f) byproduct hazards; g) potential cross-contamination; h) disposal matters; i) any mandatory regulatory requirements. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Testing and approval

9.1 General

9.1.1 Selection of test procedures depends upon location, design, configuration and application of the

separative device. 9.1.2 If air supply and exhaust systems are an integral part of the separative device, these systems shall also be tested. 9.1.3 In some situations, the air cleanliness in the separative device is not measurable by ISO 14644-1. Therefore alternative test procedures are required. EXAMPLE 1 Testing of molecular contamination [18] [19]. EXAMPLE 2 Testing by particle surface contamination [30]. 9.1.4 Certain conditions or operational states (e.g. dusty materials, out-gassing materials, or both types of materials) may not permit particulate sampling during operations or would present a hazard. Alternative states (e.g. before and after operations, but still in the operational state) may need to be sampled to determine the possibility of intrinsic contamination. 9.1.5 In the case of small-volume separative devices, a risk exists that pressure integrity and particle/aero- biocontamination counts are affected by the sample airflow rate of the air sampling instrument, if the sample airflow rate of the instrument is similar to the airflow rate of the separative device. 9.1.6 Appropriate test parameters shall be agreed between customer and supplier.

9.1.7 Separative device and auxiliary equipment testing and approval shall generally be performed with

reference to ISO 14644-1, 14644-2, 14644-3, and 14644-4. Guidance is given in the annexes in this part of ISO 14644.

9.2 Glove breach test

When appropriate, the airflow through one open glove port shall be measured by placing an anemometer at the centre of the glove port. The velocity shall be agreed between customer and supplier (guidance value: 0,5 m/s).

9.3 Operating differential pressure

9.3.1 The differential pressure shall be tested in the at-rest and operational states.

9.3.2 When devices depend on differential pressure, the differential pressure should be continuously

monitored and alarmed.

9.4 Leak testing

9.4.1 When appropriate, a leak test shall be performed. Guidance is given in Annexes E and F. NOTE Integrity testing on some separative devices that operate close to atmosphere pressure (less than 1 000 Pa) requires detailed procedures and sensitive test equipment to establish a quantifiable leak rate. The resulting leak determines acceptability for the intended application (see Annex A). 9.4.2 When appropriate, an induction leak test shall be performed. Guidance is given in Annex E. NOTE Induction leaks can occur when the velocity across an orifice creates a pressure depression and induces a reverse flow through the orifice (Venturi effect). Devices that operate at low differential pressures may be compromised by induction leakage. Similarly, devices that utilise over pressure or flow to minimise or prevent the transfer of unwanted matter may be at risk from induction leakage when operating under transient volume changes such as glove entry or withdrawal. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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9.5 Periodic testing

9.5.1 Testing shall be conducted in accordance with 9.5.2 and 9.5.3 and ISO 14644-1, ISO 14644-2,

ISO 14698-1 and ISO 14698-2. 9.5.2 The tests and checks are a function of the application and instrumentation/detection systems. Routine tests shall be established and recorded for comparison preventative maintenance requirements.

9.5.3 The following recommendations for testing are given:

a) half-suit/glove testing

  1. on commissioning,
  2. prior to and after completion of work,

  3. after glove/glove sleeve changes; b) pressure testing

  4. on commissioning,

  5. after any airflow or filter-pressure parameter changes,

  6. after maintenance affecting the separative device envelope or pressure control devices; c) induction testing on commissioning; d) instrumentation and alarm system testing

  7. on commissioning,

  8. after maintenance affecting the control system,

  9. at the frequency dictated by the instrumentation manufacturer,

  10. at predetermined periods consistent with use and operational requirements.

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Annex A (informative)

Separation continuum concept A separative device utilises physical means, aerodynamic means, or both, to create improved levels of separation between the inside and outside of a defined volume. Physical separation means include both rigid and flexible barriers. Aerodynamic means include air/gas flow with or without filtration. Generally, the assurance of maintaining separation increases with the degree of rigidity of the physical separation, as shown schematically in Figure A.1. Examples of common types of separative device for a variety of applications are given in Table A.1. However, it must be emphasised that there is not a direct relationship between airborne particulate cleanliness class, as defined in ISO 14644-1, and the position of a separative device in the separation continuum. Two measures of this separation are the separation descriptor and the hourly leak rate (pressure integrity). The separation descriptor [Aa:Bb] is a convenient measure when the hourly leak rate is not appropriate [25]. A four-level classification system of hourly leak rate (Rh) is given in ISO 10648-2. ISO 10648-2 classification is generally applied to devices with rigid physical barriers. It is acknowledged that overlap exists with ISO 14644-4, particularly with the first three items of the Figure A.1.

Figure A.1 — Schematic of the separation continuum illustrating increasing assurance of maintaining separation as the separation ranges from aerodynamic to physical means with overlapping separation approaches as a parameter Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Table A.1 — Separation continuum Separation approaches Means Device descriptor Examples of terms in common usage and synonyms Unrestricted air overspill Aerodynamic measures and filtration Open — no curtains or screens. Operator equipped with normal cleanroom garments and gloves may reach into device for access and transfer. Clean zone is at positive pressure. Clean air device, laminar flow hood, clean air hood Restricted air overspill Aerodynamic and physical Access severely restricted by curtains or fixed screens. Laminar-flow hood, clean air hood, directed air hood, clean work station Nominally enclosed — not capable of contained/ controlled atmosphere operation Aerodynamic and physical Nominally enclosed; may incorporate access devices and transfer devices. Point-of-fill device, filling tunnel Nominally enclosed — may be capable of contained/controlled atmosphere operation — single or dual mode Aerodynamic and physical Large degree of physical separation in design. May be capable of controlled/ contained atmosphere operation. Filling tunnel, point-of-fill device, laminar-flow tunnel, clean tunnel, sterilising oven, mini-environments for electronics Closed/undefined pressure integrity — performance may be hourly leak rate or other parameter Physical Closed devices with undefined integrity. May have flexible film walls. Isolators, glove bags, powder transfer control or hopper, flexible film/half-suit isolator, mini-environments for electronics Low pressure integrity/high hourly leak rate enclosure — positive or negative pressure operation Physical Rigid construction allows pressure integrity test of leak rate. May be operated under negative pressure. Isolators, gloveboxes, powder transfer control or hopper, animal test house isolator, biochemical instructional isolators; containment enclosures Medium pressure integrity/medium hourly leak rate enclosure — positive or negative pressure operation Physical Medium pressure integrity. Isolators, gloveboxes, containment enclosures High pressure integrity/low hourly leak rate enclosure — positive or negative pressure operation Physical High pressure integrity, vacuum and inert gas operation, containment at molecular level. Isolators, gloveboxes, nuclear glove box, low molecular containment enclosures NOTE 1 Examples are not design specifications or recommendations. NOTE 2 Device boundaries may overlap. Dual mode separative devices usually have a large degree of physical separation in their design, and may be capable of either open or contained atmosphere operation during specific periods of their operation. Air/gas supplied to a separative device should be of sufficient quality to comply with one or more of the classes described in ISO 14644-1. The configuration of the airflow supplied will be application specific. Both dynamic and static conditions should be specified with regard to a) air cleanliness required in the separative device, Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 18 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

b) hourly leak rate or separation descriptor, or both, c) material ingress (transfer devices), d) material egress (transfer devices).

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Annex B (informative)

Air-handling systems and gas systems B.1 General B.1.1 It is normal to protect the extract or exhaust system by an internally-fitted safe change filter. B.1.2 Over-pressure in a separative device can be avoided by the use of an oil-filled pressure-relief device. The discharge of the pressure-relief device is connected to the exhaust gas system. B.2 Air-handling systems B.2.1 Separative device air-handling systems are required to be capable of supplying or extracting sufficient air volume to or from a separative device via the installed filters and associated ductwork of the device. B.2.2 Air-handling systems should be capable of the following functions: a) isolating the separative device by valves or sealing plates upstream and downstream of inlet and outlet filtration for safety, decontamination/sterilisation/sanitation/disinfection and integrity testing purposes; NOTE This does not apply to unrestricted air overspill, restricted air overspill and nominally enclosed separative devices. b) allowing connections and any other provisions for treatment of air; c) accommodating the total system initial pressure drop and final pressure drop, allowing for filter loading; d) changing potentially contaminated filters via a safe change-filter operation that ensures contaminated filters are safely changed. Provision of operator and third-party protection is essential; e) providing all filters and associated seals with aerosol testing facilities; f) having secondary HEPA/ULPA filters on any recirculated air; g) having instrumentation to show separative-device operating pressure/depression and provision for fan/blower failure alarms; h) having, if required, particle sampling ports to enable air quality to be sampled in the separative device and its transfer devices; i) maintaining the separative-device extraction systems at negative pressure; j) ensuring, in the event of glove loss and alarm, capability of an airflow with minimum breach velocity to provide protection to either operator or product; k) complying with any other equipment or device required by local regulations. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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B.3 Gas systems B.3.1 Introduction Separative devices with high pressure integrity are normally required for molecular levels necessary for anaerobic or low moisture applications. Inert gas systems should only be used with special precautions and only on equipment designed for their application. Inert gases can kill by asphyxiation. Gas systems are either “once through” or recirculating. B.3.2 Inert gas systems Inert-gas separative devices can provide an atmosphere almost free from oxygen and moisture. The three main gases in general use, and in order of cost, are a) nitrogen, b) helium, c) argon. The applications of inert systems are various and wide ranging. B.3.3 Active gases Active gases, e.g. ozone, hydrogen peroxide, chlorine dioxide, peracetic acid and steam, may be used for decontamination purposes [24] [31]. B.3.4 Single-pass gas system Single-pass gas systems provide flow of gas through the separative devices without recirculation of the gas. Gases from bottled or stored systems should be reduced in pressure before admittance to a flow regulator. From the flow regulator, the gas is piped to the inlet valve and a gas swirler or distribution head, mounted inside the separative device. The gas is swirled to the extremities of the separative device before exiting via an extract valve to discharge. B.3.5 Inert gas recirculation systems Inert gas recirculation systems may be comprised of the following elements: a) recirculation pump; b) catalytic column(s); c) molecular column(s); d) vacuum pump; e) protection column (optional); f) inlet filter; g) associated valves; h) charge gas; i) reforming gas system; Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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j) exhaust gas systems; k) heat exchangers; l) moisture meter; m) oxygen meter; n) pressure gauge. A pump is used to recirculate gas. The gas passes through the inlet filter, inlet isolation valve and swirler into the separative device, similar to the single-pass system. The return from the separative device passes through a HEPA filter and isolating valve to a molecular column(s), catalytic column, or both. If solvents or other substances are released, the pump suctions and service columns should be protected by a suitable protective column containing for example activated charcoal or an appropriate absorber. Normal practice would be to fit two columns of each type, one in use and one reforming. Molecular columns are reformed by heating and vacuuming down. Catalytic columns are heated and purged with hydrogen/inert gas mix. Separative-device pressure is maintained by a charge-gas system in conjunction with a low-level pressure switch monitoring separative-device pressure. Overpressure requires a pressure-relief system. Transfer devices should be of the B2 class referred to in Annex D. B.3.6 Pressure-relief device The pressure-relief device allows rapid volume changes (e.g. insertion of gloves) to bubble off via the pressure-relief assembly without breaching the inert atmosphere (see Figure B.1).

Key end panel from HEPA filter oil level Figure B.1 — Pressure-relief assembly

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Annex C (informative)

Access devices C.1 Scope This annex is intended to be tutorial in nature but not exhaustive. The application of this annex is limited to gloves, gauntlets, glove sleeve systems and half-suits. Gloves tend to form the weakest link in the pressure integrity of a separative device. Operator and product protection is limited by choice of glove system and glove material. C.2 Glove materials Glove material should be appropriate for the application and process. The following list of materials gives an outline guidance but is not exhaustive. As new materials are developed, this list may expand. For full information, glove manufacturers should be consulted. a) Latex, natural rubber or cis-1,4-polyisoprene Latex, natural rubber or cis-1,4-polyisoprene is suitable in cases where great flexibility and good mechanical properties are necessary. However, latex articles are not impermeable to gas, perish in ozone, offer no resistance to flame, hydrocarbons and oxidizing salts and poor resistance to esters, acids and bases. The potential of life-threatening allergic reactions should be considered. b) Polychloroprene or poly(2-chloro-1,3-butadiene) Polychloroprene or poly(2-chloro-1,3-butadiene) is especially recommended when good resistance to oils and greases is needed. This chloroprene is self-extinguishing, i.e. when the source of ignition is removed it no longer continues to burn. Polychloroprene is highly resistant to ozone, ultraviolet light, concentrated acids and bases, and strong oxidising agents. Polychloroprene articles are unsuitable for work with hydrocarbons, halogens and esters. c) Nitrile rubber or copolymer of butadiene and acrylonitrile Nitrile rubber or copolymer of butadiene and acrylonitrile is recommended when good resistance to solvents is required. Nitrile articles stand up well to aliphatic hydrocarbons and hydroxyl compounds. d) Poly(vinyl chloride) Although plastic, poly(vinyl chloride) has a certain elasticity and is recommended for its good electrical properties and resistance to chemical agents. e) Chlorosulfonated polyethylene Chlorosulfonated polyethylene offers very good resistance to H2O2, and its white colour allows good visual inspection. Other materials are resistant to H2O2, as well. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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C.3 Sandwich or multi-layer gloves C.3.1 In order to improve the gas impermeability, sandwich or multi-layer gloves are made up of a polychloroprene base, a layer of butyl rubber and an outer layer of polychloroprene. The resulting glove possesses all the technological qualities of polychloroprene but is more impermeable to gases due to the butyl layer. C.3.2 In the special case where resistance to strong oxidising agents is inadequate, polychloroprene gloves can be coated with a chlorosulfonated polyethylene-based protective layer. The chlorosulfonated polyethylene then provides protection against all strong oxidising agents. C.3.3 In the event of even stricter conditions of use, the polychloroprene can be coated with a fluoroelastomer terpolymer, which has an excellent resistance to oils, essences, lubricants, most inorganic acids and many aliphatic and aromatic hydrocarbons (e.g. carbon tetrachloride, toluene, benzene and xylene). C.3.4 Poly(vinyl chloride) loaded with lead provides an ionizing-radiation-shielding film. These type of gloves, which require delicate handling, are normally worn as a pre-glove or inner glove. C.4 Glove size C.4.1 General Separative-device gloves are made in a range of standards sizes. If several operators are required to work on the same device, the size of the largest hand is naturally chosen. When several operators use the same glove, consideration should be given to hygiene. C.4.2 Length of glove or sleeving The length of the glove is chosen in accordance with the depth of the separative device. Typical lengths are 700 mm, 750 mm and 800 mm. The length of the sleeving is chosen as a function of the application. C.4.3 Shape of the glove Glove shapes are ambidextrous, left-hand and right-hand. For a separative device with several openings, adoption of the ambidextrous glove is advised, permitting use of the same glove with either the left or the right hand. Several cuff shapes are also available, such as conical, telescopic and cylindrical. C.5 Available thickness Varying thicknesses are available and should be selected as a function of tactile requirement, permeability, chemical resistance, mechanical strength and wear resistance. C.6 Glove ports C.6.1 The gloves or sleeves attached to separative devices are usually mechanically retained. C.6.2 Glove ports may have a glove-port “bung” facility. The glove-port bung is a removable item that can provide a high integrity seal when a glove or glove sleeve system is not in use. C.6.3 The examples in C.6.3.1 and C.6.3.2 are two of the many methods for glove or glove sleeve system replacements. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 24 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

C.6.3.1 The following instructions are provided for glove/glove-sleeve replacement using a glove-port bung, assuming the glove-port bung is fitted in position. a) Remove glove-strap assembly, gaiter extrusion and O-ring groove on glove port. b) Slip replacement glove over old glove and engage O-ring bead of glove into inner O-ring groove on port. c) Through new glove, ease old glove off port so that it is loose inside new glove. Care should be taken not to dislodge new glove. d) Replace O-ring, gaiter extrusion and glove-strap assembly, securing new glove in position. e) Place hand in new glove, remove bung and pass old glove into separative device in readiness to be bagged out. C.6.3.2 The design of the glove port allows the sleeves and gloves or gauntlets to be changed without using glove-port bungs, thereby minimising the risk of breaching separative-device conditions. See Figures C.1 and C.2 for aid in the sleeve-changing procedure. Instructions for replacement are provided as follows. a) Ensure that the new sleeve to be used is fitted with a cuff ring and glove; b) Remove the security clamp gaiter and O-ring and then, with extreme care, manoeuvre the elasticised hem of the sleeve or gauntlet from the second to the first groove of the port; c) Fit the new sleeve or gauntlet by passing the elasticised hem over the existing sleeve and onto the second groove of the port (nearest to separative device); d) Working from within the new glove, carefully manoeuvre the old sleeve hem out of the first groove of the port, and remove into the separative-device interior for future use or remove from the unit altogether via the pass-box door or bag-out facility; e) Finally, replace O-ring gaiter and metal clamp to secure the new hem in the first groove. C.7 Sleeves and gloves C.7.1 Description The sleeves have cuffs that are elasticised to provide a good secure grip. The sleeves are attached to the glove ports and are securely fastened by the action of an O-ring gaiter and metal clamp in a similar manner to a gauntlet glove. The opposite ends of the sleeves are fitted with interchangeable glove cuff rings. C.7.2 Changing gloves It is possible to change gloves minimising risk of breaching work zone atmosphere by simply removing the old glove from the cuff ring. A sterile change method is recommended. As an example, by following the instructions while referencing Figures C.2 a) to C.2 c), a “safe change” of gloves (without breaking the integrity of the system) is relatively easy. However, the glove-change system should be practised on a regular basis to ensure all operators performing the task are competent at this procedure. Instructions for replacement are provided as follows. a) Place a new pair of gloves into the working zone via the transfer device; b) Remove the glove security O-ring; Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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c) Manoeuvre the glove-cuff bead from the centre groove of the cuff ring into the outer groove, taking care not to break the air seal formed by the glove on the cuff ring [see Figure C.2 a)]; d) Pull the glove gently up inside the sleeve and hold it [see Figure C.2 b)]; e) Take the new glove and shake it straight. Align the new glove, using the free hand, so that the thumb of the glove points upwards. Using the thumb of the hand inside the sleeve, trap the glove-cuff bead onto the centre groove of the cuff ring. Gently stretch the glove cuff into the centre groove with the free hand [see Figure C.2 c)]; f) With the fingers of the hand holding the old glove, gently ease the old glove off the cuff ring at one point and work the old glove around the diameter of the cuff ring until it is free. The glove is now inside out and can be removed from the sleeve and discarded as contaminated waste; g) Refit the glove security O-ring, holding the O-ring in position initially through the wall of the sleeve with a finger or thumb.

Key glove strap assembly gaiter extrusion O-ring seal seal separative-device shell (inside) glove glove port Figure C.1 — Glove port and glove assembly Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 26 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Key glove glove O-ring cuff ring sleeve O-ring sleeve sleeve bead glove bead a) Glove-change procedure — Step 1

Key old glove bead sleeve O-ring sleeve old glove sleeve bead b) Glove-change procedure — Step 2 Figure C.2 — Glove-change procedure Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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Key new glove old glove bead new glove bead sleeve O-ring sleeve old glove sleeve bead c) Glove-change procedure — Step 3 Figure C.2 — Glove-change procedure (continued) C.8 Half-suits C.8.1 A half-suit normally consists of a double-lined suit usually manufactured from a welded flexible poly(vinyl chloride) with a clear rigid acrylic vision panel welded into the helmet section. The half-suits are attached to the separative device and are normally positioned for vertical access. C.8.2 The double lining allows the suit to be pressurised between the linings for use in positive-pressure applications, thus preventing the suit “clamping” onto the operator and restricting movement. Single-skin half- suits can be used on negative-pressure applications. C.8.3 Half-suits should incorporate suspension points to allow for elasticised fastenings to hold the suit in a suitable attitude and minimise suit-weight burden beyond ergonomic limits. C.8.4 Attachment of glove to suit is similar to the glove-sleeve cuff arrangement.

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 28 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Annex D (informative)

Examples of transfer devices D.1 Introduction This annex provides examples of transfer devices referred to in 7.2. These diagrams are only intended to be illustrated examples of possible configurations and are not normative design specifications [26]. The examples are not exhaustive. D.2 A1 transfer device When operated in accordance with a validated transfer procedure, air can flow freely through the A1 transfer device (see Figure D.1) between the background environment and the separative-device environment when the door is open. EXAMPLES Doors, access panels, zips, hook and loop tape, poppers and “jam pot” covers, bag-in-bag-out.

Key separative-device environment background environment ingress egress sealed door work surface of controlled workspace Figure D.1 — A1 transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 29 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.3 A2 transfer device When operated in accordance with a validated transfer procedure in a dynamic state, air flows freely through the A2 transfer device (see Figure D.2) out of the separative device environment. EXAMPLES Dynamic holes, mouse holes.

Key separative-device environment background environment ingress egress airflow work surface of controlled workspace Figure D.2 — A2 transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 30 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.4 B1 transfer device The B1 transfer device (see Figure D.3), when operated in accordance with a correct sequence or interlocked transfer procedure, does not permit the direct passage of air between the background environment and separative-device environment. However, air from the background environment can be trapped and then released into the separative-device environment, and air from the separative-device environment can be trapped and released into the background environment. EXAMPLES Double-door sealed transfer chambers, bagging ports, telescopic waste ports and simple docking devices.

Key separative-device environment background environment ingress egress sealed door work surface of controlled workspace Figure D.3 — B1 transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 31 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.5 B2 transfer device The B2 transfer device (see Figure D.4) has double sealed doors and facilities that permit the purging and evacuation of the transfer device to ensure compatibility of environments before breaching the interconnection to the separative-device environment. Evacuation gases require safe disposal. NOTE Evacuation may not be possible with liquid transfer, depending on the liquid boiling point/pressure relationship.

Key separative-device environment background environment ingress egress sealed door work surface of controlled workspace valve Figure D.4 — B2 transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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D.6 C1 transfer device The C1 transfer device (see Figure D.5) has doors and HEPA filters which, when used in a positive-pressure separative device and operated in the correct sequence, do not allow unfiltered air from the background environment to reach the separative-device environment but which may allow unfiltered air from the separative-device environment to reach the background environment. Such transfer devices are not suitable for negative-pressure separative devices because unfiltered air from the background environment would be allowed to reach the separative-device environment. C1 transfer devices are not recommended where operator and third-party protection is required in positive-pressure separative devices. EXAMPLE Single-filtered transfer chambers.

Key separative-device environment airflow background environment HEPA filter positive pressure ingress egress sealed door work surface of controlled workspace Figure D.5 — C1 transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 33 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.7 C2 transfer device The C2 transfer device (see Figure D.6) has doors and HEPA filters which, when used in a negative-pressure separative device and operated in the correct sequence or interlocked transfer procedure, do not allow unfiltered air from the background environment to reach the separative-device environment (such air passes straight into the space below the work surface of the separative-device environment and then exits through an exhaust) or unfiltered air from the separative-device environment to reach the background environment with the separative device in an operational state. Such transfer devices are not appropriate for use with a positive- pressure separative device. EXAMPLE Single-filtered transfer chambers.

Key separative-device environment airflow background environment HEPA filter negative pressure ingress egress sealed door work surface in controlled workspace 10 exhaust Figure D.6 — C2 transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 34 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.8 D1 transfer device The D1 transfer device (see Figure D.7) has doors and HEPA filters which, when operated in the correct sequence or interlocked transfer procedure, do not permit unfiltered air from the background environment to reach the separative-device environment or unfiltered air from the separative-device environment to reach the background environment. EXAMPLES Double-filter transfer chambers, or separative devices used as a transfer device.

Key separative device environment valve background environment HEPA filter ingress egress sealed door work surface of controlled workspace Figure D.7 — D1 transfer device D.9 D2 transfer device The D2 transfer device is a D1 transfer device described in D.8 fitted with interlocked and time-delayed ingress/egress control which, when operated with a valid transfer procedure, will create a period to allow any surface decontamination procedure sufficient time to minimise transference of contamination. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 35 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.10 E transfer device The E transfer device (see Figure D.8) is subject to sanitation together with its contents, if any, before being opened into other areas which have been subject to sanitation. EXAMPLES Gassable/autoclavable transfer devices, including certain transfer separative devices and docking devices, permanently connected autoclaves and similar devices.

Key separative-device environment three-way valve quick-connect coupling background environment HEPA filter ingress egress sealed door work surface of controlled workspace Figure D.8 — E transfer device Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 36 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

D.11 F transfer device The F transfer device (see Figure D.9) docks and seals onto a separative device. The transfer device is commonly used as a transport container. Some devices may have disconnects for air bleed. EXAMPLES Rapid transfer systems, standard mechanical interfaces, and split valve connections.

Key separative-device environment background environment quick-connect coupling double interlocked doors or valves work surface or controlled workspace Figure D.9 — F transfer device

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 37 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Annex E (informative)

Leak testing E.1 Induction leak testing E.1.1 Procedures The test procedures should be applied under normal operating conditions. Where pressure or flow is used to create velocity or mass flow to minimize or prevent transfer of unwanted matter, the capability of such systems should be established by agreed, quantifiable, repeatable test procedures. The test procedures should take into consideration a) normal operation, b) at rest or standby, c) transient changes during a) and b), d) pressure or airflow failure. Where glove and glove system are used, the induction testing should include the transient volume change when all operator glove positions are inserted or withdrawn simultaneously, as significant pressure changes in excess of 1 000 Pa can be experienced. Any equipment with a similar volumetric effect should also be included in the test procedure. E.1.2 Test equipment Test equipment and procedures should be appropriate to the process. Suitable test equipment consists of a) aerosol generator and photometer, b) aerosol generator and dual-reading discrete particle counter, c) spinning-disk droplet generator or similar challenge, and appropriate detection system. E.1.3 Method Aerosol is generated outside of the separative device at the region of interest. Comparisons of the outside and inside particle concentrations are made to determine if significant penetration has occurred. Test procedures and protocols should be developed for each application. E.2 Pressure leak detection E.2.1 Major leaks can be detected by several alternative methods. The methods in E.2.1.1 and E.2.1.2 are indicative. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 38 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

E.2.1.1 Apply a good quantity of soap solution to suspected area of the separative device under test. Leaks will be apparent by bubbling of the soap solution. E.2.1.2 As a first alternative to the test in E.2.1.1, leaks may be detected by filling the separative device with helium or suitable alternative to a positive pressure of up to 1 000 Pa. Using a suitable probe, suspected areas can be monitored for leaks. NOTE 1 Neither of the methods in E.2.1.1 or E.2.1.2 is quantitative although, with tracer gas, discrimination can be made between levels of leaks. NOTE 2 Other methods can be used for locating leaks, such as pressurisation with ammonia gas and detection with wet pH-indicating cloth, or the use of visible smoke with visual, photographic or video documentation. E.2.2 The following methods, in order of increasing sensitivity, are given as guidance: a) use of bubble testing using a suitable surfactant; b) use of a thermal conductivity “sniffer” probe with CO2, He, Ar, etc.; c) use of an ionisation detector “sniffer” probe with SF6; d) use of helium mass spectrometer with “sniffer” probe with helium. It is conventionally assumed that the leakage of a separative device is evenly distributed and does not occur through a single leak path. This assumption may not be appropriate in a separative device. A single leak path could produce an unacceptable local deterioration of the atmosphere. Therefore the design should emphasise, where applicable, the prime importance of specifying a suitable leak method. Precautions should be used when using inert test gases. Inert gases can kill by asphyxiation. When using helium, care should be taken to ensure that the gas test mixture inside the device is well mixed. NOTE 1 Helium can penetrate polymeric materials and the off-gassing can create false positives. NOTE 2 More information may be found in reference [24]. E.3 Quantitative leak testing E.3.1 Pressure integrity testing E.3.1.1 Leak testing for negative pressure rigid wall separative devices ISO 10648-2 specifies three methods of leak testing for negative pressure, rigid wall separative devices described in ISO 10648-1: a) oxygen method (see ISO 10648-2:1994, 5.1); b) pressure change method (see ISO 10648-2:1994, 5.2); c) constant pressure method (see ISO 10648-2:1994, 5.3). The leak rate is measured at the normal operating pressure (usually about 250 Pa) for checking during operational use, and up to 1 000 Pa for the acceptance test. The above methods are specified for negative-pressure tests, which apart from the oxygen method can be undertaken either in positive- or negative-pressure mode. The appropriate mathematical changes needed to be undertaken when calculating the results. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 39 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

A further pressure-test method (Parjo), which can be applied over the same hourly leak-rate range as the above methods, is also included in Annex F. The Parjo test may be appropriate for conditions requiring minimisation of contamination of the test equipment or reduction of test times. Pressure tests at close to atmospheric conditions are subject to changes in temperature and ambient parameters. The use of sensitive instruments to measure parameters will greatly contribute to the accuracy of these tests. Separative devices that may, during normal operation or system failure, experience both positive and negative modes should establish quantitative leakage rates in both states. E.3.1.2 Pre-test precautions The integrity pressure testing will likely be applied only in instances where minimal risks are involved. However, any test carries some small degree of risk to equipment and operator. During the acceptance test, the safety precautions to be observed are essentially common-sense and related to excessive over- or under-pressure conditions of the separative device under test. The specific proof test pressure should never be exceeded, since structural damage can be caused to thin walls, etc. Depression tests are also liable to cause damage, i.e. collapsing of light structures. When testing equipment for high or medium pressure integrity, a more questioning approach is required. An isolation pressure rise test, i.e. a leak rate test, requires a constant volume. These test methods are highly sensitive to small volume changes, therefore any installed equipment which may be liable to a volume change can not only lead to spurious result but also allow the release of materials, e.g. oil and grease. If inert gas from pressurised containers is to be used as a test medium, the necessary pressure relief and regulation equipment must be installed and checked before tests are carried out. (Refer to appropriate precautions in the handling, storage and use of compressed gases.) The leak rate testing of “active” separative devices demands special attention. It is imperative that local safety regulations be followed. Before testing is contemplated, a thorough enquiry should be completed. The enquiry should ensure that isolation of the separative device can be carried out in a logical and safe manner that allows a rapid return to normal operating conditions in the event of an emergency. When tests have been completed or postponed, it is important to ensure that the separative device is made safe, especially if left unattended overnight in unheated conditions. A temperature drop of a few degrees can cause considerable stress on a thin-wall section left in negative-pressure conditions. E.3.1.3 Achieving stable conditions Before any leak rate test can be started, the separative device should be in a quiescent state. Where possible and practicable, separative devices that are liable to change volume by “panting” or movement of panels or other light structures should be constrained during the test period. The allowable leak rate and the sensitivity required to detect the rate are important factors. If very low leak rates are required, achieving a stable condition is sometimes difficult due to climatic changes. If practicable, the separative device should be insulated. Small changes in ambient conditions can produce apparent leak rates approaching or even exceeding allowable rates. The separative device under test needs to be in an area free from the effects of direct sunlight and drafts. To ensure that all equipment is at the same temperature, the test equipment should be in position approximately 30 min prior to the test, or longer if possible. Maintaining stable ambient conditions can be difficult. If the necessary stability cannot be maintained for the test period, then the test should be conducted before or after normal working hours. The testing of separative devices in a controlled atmosphere can present some difficulties. Inadequate or faulty controls can cause sudden variations in the atmospheric pressure, and access through airlock doors may need to be restricted while observations are proceeding. It is essential to consider the relevant safety orders in force. The best approach may be to carry out the test during quiet hours or during meal breaks. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 40 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

E.3.1.4 Equation development Velocity through an orifice, assuming the orifice and expansion coefficients are unity, is given by 2 p v ρ ∆

(E.1) where v is the velocity, in metres per second; ρ is the density, in kilograms per cubic metre (dry air = 1,205 kg⋅m–3 at 101,3 kPa, 20 °C); ∆p is the differential pressure, in pascals, across the orifice. Volumetric flow rate is equal to velocity times area, therefore 3 600 p q A ρ ∆

× ×

(E.2) where q is the hourly leakage from the separative device, in cubic metres per hour; A is the area, in square metres. Substituting 1,28 1,205 ρ =

(E.3) 1,28 3 600 q A p

× ∆

(E.4) NOTE 1 Orifice size and differential pressure are the only considerations in calculating the leak flow rate. NOTE 2 Potential risks from leaks require careful assessment. Inward leakage in negative-pressure devices through small orifices tend to produce high-velocity jets of potential contamination that are unlikely to be diluted by the airflow of the separative device. Similarly, positive-pressure devices that have similar outward leaks can create unacceptable localised contamination. The test methods in Clause E.3 for constant-volume separative devices follow the combined Gas Law equation (in absolute terms): p V p V T T ⋅ ⋅

(E.5) where p is the absolute pressure, in pascals; T is the absolute temperature, in kelvins; V is the volume of the separative device, in cubic metres. NOTE 1 For a constant volume, 1 K variation in temperature will cause a 334 Pa variation in pressure. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 41 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

NOTE 2 The test procedures (except for Parjo) are conducted for 1 h duration and an initial test pressure at or above 1 kPa. The volume of the gas leaking (in or out) is proportional to the pressure change when corrected for any barometer and temperature changes. By maintaining constant volume and factoring volume from both sides of the equation, the formula becomes: p p V T T  

   

(E.6) The test procedures in Clause E.3 are conducted for 1 h duration and an initial test pressure at or above 1 000 Pa for commissioning. The volume of gas leaking either in or out of the total test volume (constant) is proportional to the pressure change. Therefore, the hourly leak rate is equal to the fractional pressure change in one hour. Changes in temperature and barometric pressure during the test require corrections to the hourly leak rate as shown by Equation (E.6). E.3.1.5 Hourly leak rate The hourly leak rate Rh of the separative device, expressed in reciprocal hours (h–1), is given by: h q R V

(E.7) where q is the hourly leakage of the separative device, in cubic metres per hour; V is the volume of the device, in cubic metres. NOTE With the exception of the oxygen test, the test methods assume constant-volume rigid structure devices. Thin- or flexible-system leakage rates obtained by pressure methods will vary due to volume changes. Gloves and half-suits should be blanked off during containment leak tests using other than the oxygen method. E.3.1.6 Classification The classification of separative devices according to hourly leakage rate is shown in Table E.1. Table E.1 — Classification of separative devices and appropriate test methods Class Hourly leak rate Rh h–1 Pressure integrity Test methods u 5 × 10–4 High Oxygen method, pressure change method or Parjo method < 2,5 × 10–3 Medium Oxygen method, pressure change method or Parjo method < 10–2 Low Oxygen method, pressure change method or constant pressure method < 10–1

Constant pressure method NOTE 1 The classification and specified test methods in ISO 10648-2 were combined with pressure integrity levels to allow comparison with the separation continuum in Annex A. NOTE 2 Parjo method was included where appropriate. NOTE 3 ISO 10648-2 test methods apply to negative-pressure separative devices but can be modified for positive-pressure separative devices, with the exception of the oxygen method. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 42 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

E.3.2 Mass balance method for estimation of acceptable hourly leak rate E.3.2.1 Rationale The rationale is based on the fact that, where there is airborne contamination on the outside of a negative- pressure separative device, flow through the leak allows this airborne contamination to reach the inside of the separative device. Where there is airborne contamination on the inside of a positive-pressure separative device, flow through the leak allows this airborne contamination to reach the background environment around the separative device. In both cases, the concentration of the leak can be diluted by any airflow in the space that it enters. A mass balance equation is used to estimate the hourly leak rate from the equilibrium concentration of contaminant in the two air volumes connected by the leak. E.3.2.2 Limitations E.3.2.2.1 The calculations do not take into account local conditions at a leak where the level of contamination from the leak may not have been diluted to the acceptable level. In practice, a significant safety factor should be allowed to minimise local effects. E.3.2.2.2 It is assumed that a risk analysis has been used to establish the maximum acceptable concentration of contaminant, with respect to product quality in the case of negative-pressure separative devices or with respect to operator safety in the case of positive-pressure separative devices. It is assumed that  the concentration of contaminant in the leak is the same as the concentration of contaminant in the upstream (higher pressure) space,  air in the space affected by the leak is well mixed (which is not the expected condition in unidirectional or low velocity airflow),  air mixing with the leak has no initial concentration of contaminant,  the process has reached a steady state. E.3.2.3 Estimation The hourly leak rate, subject to the limitations in E.3.2.2, is estimated by the following equation: ac a s h V R c R c V

(E.8) where Rh is the hourly leak rate, in reciprocal hours (h−1); Vs is the volume of the space affected by the leak, in cubic metres; ca is the acceptable concentration of airborne contamination in the space affected by the leak, in millilitres per cubic metre (or any other suitable measure); Rac is the air change rate in the space affected by the leak, in reciprocal hours (h−1); c1 is original concentration of airborne contamination in the leak itself, in millilitres per cubic metre (or in the same units as ca); V is the volume of the separative device, in cubic metres. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 43 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

This formula is written so it can apply to the inside space of a negative-pressure separative device or to the background environment space of a positive-pressure separative device. E.4 Quantitative leak testing of flexible-film separative devices E.4.1 Flexible-film separative devices may be damaged during testing with differential pressures excessively greater than operating pressures. E.4.2 Flexible-film separative devices should be tested using the oxygen method. NOTE Once quantitative acceptance results have been obtained, it is worthwhile to undertake a positive-pressure test for comparative routine testing at operating pressures, especially for a separative device that should not be compromised by the use of negative-pressure testing, e.g. a sterile separative device. Separative devices that cannot achieve the classification acceptance test pressure of 1 000 Pa but still require an hourly leak rate for hazard analysis purposes should test at 250 Pa for times less than 1 h. The resulting hourly leak rate should be doubled for the purposes of analysis [see Equation (E.4)]. E.5 Examples of glove leak tests E.5.1 General The pressure decay tests described are only a few of many tests that can be used for glove testing and are intended to illustrate glove leak test procedures. Other glove leak test methods may be used as agreed by customer and supplier in appropriate situations. E.5.2 Test for negative-pressure separative devices E.5.2.1 Overview Visual inspection of gloves is important, as pressure may not reveal possible “self-sealing” damage. The test in E.5.2.2 describes a simple method for testing gloves for leaks in negative-pressure separative devices operating at a pressure drop greater than – 170 Pa. The in situ glove-leak tester is comprised of a sensitive manometer or similar device fitted to a sealing plate. This is suitable for testing gloves/gauntlets/glove sleeve systems fitted to glove ports. E.5.2.2 Method of operation To perform the test, the following procedure is recommended. a) Switch on the manometer. b) If the manometer has a HI-LO range switch, select the LO range setting. c) Adjust the manometer to zero. Small variations of ± 3 Pa to ± 4 Pa from zero will not adversely effect the result or the sensitivity of the tests. Once the unit has been “zeroed”, the unit can be used to test the integrity of gloves/gauntlets. d) Gently position the sealing plate of the glove-leak tester against the glove-port ring of the glove/gauntlet to be tested, taking care to ensure that the sealing plate is aligned with the glove port. Forceful positioning of the unit may trap a small positive pressure of air between the unit and the glove. e) Press the unit firmly against the glove port with a constant force, and carefully observe the reading of the manometer. The action of pressing the unit with different forces may cause fluctuations of ± 3 Pa to ± 4 Pa; again, this will not adversely effect the results or sensitivity of the tests. With experience, Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 44 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

operators will be able to identify potential problems in a 10 s test period. Suspect gloves/gauntlets should be re-tested, and a longer test period may be required to confirm results. f) Test all the gloves/gauntlets on fitting and prior to operating the separative device. E.5.2.3 Results E.5.2.3.1 Pass If the glove/gauntlet is sound, then the reading shown on the manometer will remain static within ± 2 Pa to ± 10 Pa (or, better, ± 5 Pa). E.5.2.3.2 Fail If the glove/gauntlet is damaged, then the reading shown on the manometer will become increasingly negative (i.e. − 10 Pa, − 15 Pa, − 19 Pa). This trend will be distinct and progressive. The rate of change will be proportional to the level of damage to the glove's integrity. Any test showing probable damage should be repeated; this is easily done by releasing the pressure of the test unit against the glove port, which will allow the manometer to return to zero, and then reapplying pressure to start the retest. A damaged glove/gauntlet will create the same response pattern in each test, making confirmation an easy process. E.5.2.4 Sensitivity The test is proportionally sensitive to the decrease in internal operating pressure of the separative devices. Higher decrease in internal operating pressure provides more distinct test results, as shown in Equation (E.4). Therefore, doubling the decrease will nearly double the leak rate. For small pressure drops, the leak rate closely follows a linear equation. E.5.3 Positive-pressure glove-leak tester E.5.3.1 Overview A positive-pressure leak-testing system requires a sealing cap to cover the glove/gauntlet aperture, which is fitted with two pipe fittings. One fitting is used to connect a sensitive valve for admitting and releasing the pressurizing gas. The second fitting is used to attach an electronic micromanometer. This method should only be used before decontamination, and is not an in-process test. E.5.3.2 Test procedure When the sealing cap is placed over the glove-port ring, a space is formed between the cap and the inside surface of the glove. This space is then pressurised to 1 000 Pa and allowed to stabilise. A drop in this pressure will indicate a leak through the glove fabric or securing arrangement. The following steps should be followed. a) Prior to commencement of test it is important to visually inspect the glove/gauntlets for any obvious damage. b) Make sure all fingers on the glove extend into the separative device. c) Connect the air line to the separative device. d) Switch on the manometer. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 45 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

e) Adjust manometer to zero by pressing the “zeroing button” while holding the glove-leak tester in free space. Small variations of ± 3 Pa to ± 4 Pa from zero will not adversely affect the result or the sensitivity of the tests. f) Fit the sealing cap of the glove-leak tester over the outer port ring of the glove to be tested. g) Inflate the glove by operating the valve. The gauge of the manometer will display the pressure within the glove in pascals. The glove should be inflated to a minimum of 500 Pa and a maximum of 1 000 Pa; this may take a number of injections of air to reach the required pressure as the system stabilizes. h) Observe the reading on the manometer. A stable reading will indicate a sound glove. With experience, operators will be able to identify potential problems in a 10 s test period. Suspect gloves/gauntlets should be re-tested, and a longer test period may be required to confirm results. E.5.3.3 Results E.5.3.3.1 Pass If the glove/gauntlet is sound, then the reading shown on the manometer will remain static within 2 Pa to 10 Pa, subject to the small variations noted in E.5.3.2. E.5.3.3.2 Fail If the glove/gauntlet is damaged, then the reading shown on the manometer will fall (i.e. 500 Pa, 495 Pa, 490 Pa). This trend will be distinct and progressive. The rate of change will be proportional to the level of damage to the integrity of the glove. Any test showing probable damage should be repeated. Any tests that record a distinct change in pressure should be closely investigated and the fault (e.g. incorrectly positioned cuff ring, damaged glove) either re-tested or the suspect glove/gauntlet changed and a successful test conducted. E.6 Example of leak tests for half-suits E.6.1 Acceptance testing for equipment containing flexible half-suits may be undertaken using the oxygen method described in ISO 10648-2. E.6.2 After quantitative acceptance results have be obtained, it may be worthwhile to undertake pressure tests for comparative routine testing, particularly to avoid compromising the integrity of the device by the use of negative-pressure testing.

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 46 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Annex F (informative)

Parjo leak test method F.1 Background Parjo is the name given to a method for the leak rate assessment of separative devices operating at pressures close to atmospheric. The method was originated by and named after K. Parkinson and W. F. Jones. This test provides a (relatively) quick and versatile method of determining leak rates. It can be used on contaminated devices providing the pressure tapping is suitability protected, thus avoiding lengthy down times, as there are no intrusive test instruments. The short duration of the test tends to reduce effects of changes in temperature and atmospheric pressure. It is a sensitive test for minor leaks [12]. F.2 Test for major leaks F.2.1 General Procedures for detection of major leak are provided in E.2.1 and should be undertaken on new equipment prior to using the Parjo leak test procedures. F.2.2 Principle The Parjo method uses a pressure-sensitive detergent film (meniscus) injected into a glass tube of known dimensions and a reference vessel of known volume. The method is capable of rapidly indicating a change of volume transmitted from the separative device to the reference vessel volume. Assume that the scheme shown in Figure F.1 is practicable. With valves A and B open, the pressure in the separative device and reference vessels will soon reach equilibrium. Then, if the valves are closed, any change in separative-device pressure is reflected by a movement of the piston (meniscus) towards the lower pressure. This movement represents a volume change. This principle is applied by using the Parjo tube shown in Figure F.4 and installed as shown in Figure F.2 or F.3. The glass walls of the reference vessel will rapidly transmit radiant heat effects in the separative device. Reasonable precautions should be taken to prevent the separative device from picking up heat radiated from external sources. Piston (meniscus) deflections will then accurately represent changes in the separative-device atmosphere and can be calculated as volume changes. If observation of the meniscus deflections are kept short, e.g. no more than 5 min, temperature and barometric variations can be ignored. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 47 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Key valve A frictionless piston pressure gauge separative device glass tube rubber bung clear glass reference vessel of known volume isolation valve B to pressure/vacuum source Figure F.1 — Schematic showing principle of operation F.3 Equipment F.3.1 General The equipment needed to carry out the test is described in F.3.2. Only items of approved design can be used and should be set up as shown. To allow the method to be used at manufacturer, laboratory or production line installations, the test equipment should be capable of insertion into the device with the minimum of break in containment. The items approved for use can be inserted and assembled through a 152 mm-diameter glove port or penetration of similar size. If the separative device does not allow insertion of the test equipment, then other arrangements should be considered (see F.3.3). Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 48 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Key connection of separative device to ductwork viewing port propipette rubber tube Parjo tube rubber stopper glass bottle manometer/gauge isolation valve 10 pressure/vacuum source Figure F.2 — Typical separative device equipment layout F.3.2 Equipment list F.3.2.1 The following Items are approved for use: a) Parjo tube Type A; b) metric scale (clip on); c) clips, spring; d) stopper, rubber, bored to suit Parjo tube of diameter either 19 mm or 21 mm; e) bottle, clear glass with a volume of 2 500 cm3; f) propipette rubber bulb with 3 valves. F.3.2.2 Other items needed which are readily available: a) rubber tubing (6 mm bore), as needed; b) U-tube manometer or capsule gauge, to cover required range; Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 49 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

c) stop watch or suitable timepiece; d) needle valve to introduce controlled leak; e) pressure/vacuum source; f) isolation valve, e.g. diaphragm type (6 mm bore); g) fittings to suit valve/ rubber hose, etc.; h) bubble solution to form meniscus (see F.3.4).

Key separative device optional HEPA filter manometer/gauge rubber tube propipette isolation valve Parjo tube rubber stopper insulated glass bottle 10 pressure/vacuum source Figure F.3 — Typical separative-device equipment layout with test equipment located external to device under test F.3.3 Design requirements To use the Parjo test method, a means of introducing the equipment into the separative device is required. The Parjo tube and scale should be clearly seen by the operator, although cold light (i.e. a hand-held, battery- powered electric light) can be used to illuminate the tube and scale. The separative device should also be fitted with a means of indicating the internal pressure, i.e. a mechanical gauge or U-tube manometer. Most separative devices have a number of penetrations of varying size. These penetrations can be readily adapted to provide a viewing window and access for the test equipment. Figures F.2 and F.3 show typical equipment layouts. Figure F.2 shows the test equipment within its own separative device, ready for connection to any system. The layout shown in Figure F.3 provides greater accessibility to the equipment. The test vessel shown in Figure F.3 should be insulated to minimise any variations in temperature. The use of in-line HEPA-filter- protected sample points allows this test procedure to be used on contaminated systems. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 50 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

If a separative device is leak-rate tested in accordance with the Parjo method, the drawings or the test schedule or both should be endorsed as shown: a) Proof test.................................Pa positive pressure b) Maximum leak rate..................Percent volume/h negative Percent volume/h positive

Key scale spring clip liquid level when charging Figure F.4 — Parjo tube type A Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 51 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

The free end of the Parjo tube is connected to the device under test by the minimum length of flexible polyvinyl chloride (PVC) tubing. In some cases, the leak rate may not be detectable. To prepare a valid test report, introduce a small acceptable leak by fitting a good quality needle valve into either the separative device or the test equipment, as convenient. Separative devices are often light structures. Under test conditions, the apparent leak may vary due to the separative-device walls or windows. For example, separative-device plastic windows flex considerably under test. Variations in atmospheric pressure can produce a significant change in the separative-device volume. The effects of ambient temperature and pressure should be minimised, and any changes should be noted. F.4 Procedure F.4.1 Preparation of Parjo tube Charge the Parjo tube with a bubble-producing solution to a level which half fills the spherically shaped reservoir (see Figure F.4). Clip the scale into position. Then connect the upper end of the U tube in which the reservoir is positioned via a rubber tube to the propipette described in F.4.3, which is positioned outside the separative device. Then pass the glass tube assembly through a rubber bung and insert the whole assembly in the reference-volume glass vessel. With stable conditions and the separative device isolated and at test pressure, form a bubble by gently squeezing the rubber bulb or the propipette until a meniscus of the solution is positioned at the intersection of the two measuring areas of the glass tube. Release the bulb pressure slowly to allow the meniscus to remain in position. A light touch is required to perform this operation. It should be noted that the propipette has three glass ball-valves incorporated in the design, and the appropriate valve should be operated when introducing a bubble. Observe the behaviour of the meniscus. If a pressure rise occurs during a negative-pressure test, the meniscus will deflect along the arm towards the reference vessel. If a pressure rise occurs during a positive- pressure test, the meniscus will deflect away from the reference vessel. F.4.2 Leak-rate test procedure A leak-rate test should be performed on each separative device, with the atmosphere within the separative device at positive pressure followed by a similar test at negative pressure. Set up test equipment as shown and proceed as follows. a) Thoroughly clean all items to be placed in the separative device. Ensure that the Parjo tube has been thoroughly cleaned and wetted as described in F.3.4. Charge solution reservoir with sufficient solution to allow adequate stock. Position reference vessel and Parjo tube to allow good reading visibility through a viewing panel. b) Seal the separative device and, using suitable equipment, reduce or pressurise the atmosphere as required by the test in progress. The test pressure shall be either + 1 000 Pa or as stated on the drawings or contract. c) Allow approximately 30 min for all the equipment to reach the same temperature. d) Inject a bubble into the Parjo tube by very gently squeezing the propipette bulb as described in F.4.2 until a meniscus of the detergent solution is positioned at the intersection of the two measuring arms of the tube. Release the bulb pressure slowly to allow the meniscus to remain in position.  If the separative-device atmosphere is at negative pressure and the device is not pressure-tight, the bubble will travel along the inclined arm of the Parjo tube towards the reference vessel. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 52 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

 If the separative-device atmosphere is at positive pressure and the device is not pressure-tight, the bubble will travel along the arm of the Parjo tube towards the outlet to the separative-device atmosphere. e) When the bubble has formed a clear meniscus in the tube, start timing the travel of the meniscus and record deflection. When taking readings, ensure there are no secondary bubbles in the discharge to either the reference vessel or the separative device. Meniscus movements in the Parjo tube are influenced by the presence of secondary bubbles close to the tube ends in either the glass reference vessel or the separative device atmosphere. Ensure that all secondary bubbles are burst before taking deflection readings. A bubble close to either exit may be burst with the propipette. f) Measure the deflection against a timed period of between 3 min to 5 min and record the results. If there is no detectable deflection, introduce a small leak within acceptable limits by opening some convenient penetration or by means of a needle valve installed for the purpose. Proceed with test certification. g) Use the F.5.4 example test certificate form to record results. During a test, an approximate leak rate can be assessed in 2 min to 3 min. A rapid movement of the bubble indicates leaks greatly in excess of the allowable, and it may not be worth considering the test an official test. However if the equipment is used while searching for leaks, then it may indicate reductions in leak rate during rectification work. Do not forget that the leak path may be unidirectional. This is particularly true of gasket-sealed blanking-off arrangements. F.4.3 Using the propipette The propipette is essentially a rubber bulb fitted with three glass ball-valves as shown in Figure F.5. To introduce a bubble into the centre of the Parjo tube measuring arms, use the following procedure. a) Ensure that there is sufficient solution in the liquid reservoir. b) Gently squeeze the bulb to create a little pressure using one hand. c) With thumb and forefinger of the other hand very gently squeeze Valve A to allow the pressure to escape from the bulb to the Parjo tube while watching the effect on the bubble solution. d) When a bubble has been formed, release hand pressure on Valve A and the bulb. e) Press Valve R to ensure any remaining pressure in the bulb is released. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 53 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Key to atmosphere Valve R bulb Valve A Valve M to Parjo tube NOTE Valves are normally closed. Figure F.5 — Diagram of the propipette F.5 Calculation of results F.5.1 General It is important that only approved equipment with known dimensions and values is used for this method. A basic method of calculation of the leak rate is given in F.5.2. F.5.2 Formula The hourly leak rate, Rh, is calculated from the formula: Rh = P r A d V t × ×

(F.1) where AP is the cross-sectional area of the Parjo tube, in square centimetres; d is the deflection of meniscus in the tube, in centimetres; Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 54 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

r V is the volume of the reference bottle, in cubic centimetres; t is the time, in minutes. The approved known reference volume, r V , is a glass bottle of either 2 500 cm3 or 2 700 cm3 capacity. The approved Parjo tube bore size is 4 mm, which gives an actual cross-section (AP) of 0,126 cm2 but for practical reasons use 0,127 cm2. Hence a deflection d (cm) of the meniscus in the tube produces a volume change of AP × d (cm3). F.5.3 Examples 0,8 cm deflection in 5 min with a 2 500 cm3 glass bottle: Rh = 0,127 0,8 4,88 h 2 500 − − × ×

×

1,0 cm deflection in 5 min with a 2 700 cm3 glass bottle: Rh = 0,127 5,64 h 2 700 − − × ×

×

1,5 cm deflection in 3 min with a 2 700 cm3 glass bottle: Rh = 0,127 1,5 1,41 10 h 2 700 − − × ×

×

F.5.4 Test certification F.5.4.1 General Presentation of results is largely dependent on the type of equipment/volume under test and the allowable leak rate. F.3.2 gives the basic dimensions of the equipment and, provided that only approved equipment is used, it should allow the user to compile a test report to suit the requirements as scheduled in the contract or other relevant document. F.4 gives the method of operation. If a detectable leak is present it will produce a deflection of the meniscus in the Parjo tube. However, the separative device may leak at a rate undetectable by this method when the observation period is kept within the recommended 5 min. This does not mean the separative device is leak- tight, and the test certificate should not state that the leak is undetectable. If the separative device is leaking at a rate not detectable by this method, a controlled leak within the allowable limit should be introduced (F.4.2) by opening a valve installed for the purpose. After an acceptable meniscus deflection has been observed and recorded against time, the valve should be closed and the deflection should stop. The operation should be checked for repeatability. The test certificate may then state that the actual leak rate does not exceed the introduced leak and is thus acceptable. Table F.1 gives a guide to deflection and time values. F.5.4.2 illustrates an example of a test certificate suitable for separative devices. It is advisable to take two or three readings when a leak is detected. If the trend indicated shows the leak is acceptable and consistent, then the average of three separate readings will allow a valid test report to be completed. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 55 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

F.5.4.2 Example of typical test certificate Hourly leak rate test using Parjo tube method Test certificate Date of test.............................................................Contract Number.................................................. Manufacturer ........................................................................................................................................ Location of test..................................................................................................................................... Drawing Number .................................................................................................................................. Separative device identification............................................................................................................ Separative device proof test pressure ............................................................................. kPa positive Separative device leak rate test pressure.......................................................................kPa negative

..................................................................... kPa positive Maximum permissible hourly leak rate ........................................................................................max. Reference vessel volume.............................................................................................................. cm3 Time tests started.............................................................Completed.................................................. (stable state achieved) Test number Test mode Deflections in tube readings Hourly leak rate

+/– in cm = d in min = t Rh

Use formula to obtain hourly leak rate Rh = P r A d V t × ×

Ref. Vol. = r V .......................................................................... cm3 Tube cross-section = AP ............................................... 0,127 cm2 Observed deflection = d ...........................................................cm Deflection time = t ...................................................................min Average hourly leak rate ................................................................ Test result * (Acceptable) As tested

(Not acceptable) Signed ............................................................................................ Witness...........................................................................................

--- PAGE 56 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

F.5.5 Hourly leak rate data Table F.1 — Hourly leak rate (h–1) data for a type A Parjo tube Deflection cm Observation time min

0,2 0,000 60 0,000 30 0,000 20 0,000 15 0,000 12 0,3 0,000 91 0,000 45 0,000 30 0,000 22 0,000 18 0,4 0,001 21 0,000 60 0,000 40 0,000 30 0,000 24 0,5 0,001 52 0,000 76 0,000 50 0,000 38 0,000 30 0,6 0,001 82 0,000 91 0,000 60 0,000 45 0,000 36 0,7 0,002 13 0,001 06 0,000 71 0,000 53 0,000 42 0,8 0,002 43 0,001 21 0,000 81 0,000 60 0,000 48 0,9 0,002 74 0,001 37 0,000 91 0,000 68 0,000 54 1,0 0,003 04 0,001 52 0,001 01 0,000 76 0,000 60 2,0 0,006 08 0,003 04 0,002 02 0,001 52 0,001 20 3,0 0,009 12 0,004 56 0,003 03 0,002 28 0,001 80 4,0 0,012 16 0,006 08 0,004 04 0,003 04 0,002 40 5,0 0,015 20 0,007 60 0,005 05 0,003 80 0,003 00 6,0 0,018 24 0,009 12 0,006 06 0,004 56 0,003 60 7,0 0,021 28 0,010 64 0,007 07 0,005 32 0,004 20 8,0 0,024 32 0,012 16 0,008 08 0,006 08 0,004 80 9,0 0,027 36 0,013 68 0,009 09 0,006 84 0,005 40 NOTE Approximate hourly leak rates using a 2 500 cm3 reference vessel.

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 57 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

Bibliography [1] ISO 10648-1, Containment enclosures — Part 1: Design principles [2] ISO 13408-1, Aseptic processing of health care products — Part 1: General requirements [3] ISO 13408-5, Aseptic processing of health care products — Part 5: Aseptic processing of solid medical devices [4] ISO 13408-6, Aseptic processing of health care products — Part 6: Isolator/barrier technologies [5] ISO 14644-5, Cleanrooms and associated controlled environments — Part 5: Operations 2) [6] EN 12296, Biotechnology — Equipment — Guidance on testing procedures for cleanability [7] EN 12298, Biotechnology — Equipment — Guidance on testing procedures for leaktightness [8] EN 12307, Biotechnology — Large-scale process and production — Guidance for good practice, procedures, training and control for personnel [9] EN 12469, Biotechnology — Performance criteria for microbiological safety cabinets [10] ENV 1631, Cleanroom technology — Design, construction and operation of cleanrooms and clean air devices [11] AECP 59, Shielded and unshielded glove boxes for “hands on” operation. United Kingdom Atomic Energy Authority (UKAEA) Harwell Laboratory, Oxfordshire, UK [12] AECP 1062, The Parjo method of leak rate testing low pressure containers. United Kingdom Atomic Energy Authority (UKAEA) Harwell Laboratory, Oxfordshire, UK [13] BS 3636, Methods for proving the gas tightness of vacuum for pressurized plants [14] IEST-RP-CC0028:2002, Minienvironments. Institute of Environmental Sciences and Technology, Rolling Meadows, Illinois, USA [15] NF 0137/1, Leak testing, Code of practice for test requirements for low working pressure containers. British Nuclear Fuels, plc, Technical Standards Group, Risley, UK [16] SEMI E19-0697:1997, Standard mechanical interface (SMIF). SEMI, San Jose, California, USA [17] SEMI E47.1-0303:2001, Provisional mechanical standard for boxes and pods used to transport and store 300-mm wafers. SEMI, San Jose, California, USA [18] SEMI E45-1101:2001, Test method for the determination of inorganic contamination from mini- environments using vapor phase decomposition/total reflection X-ray fluorescence spectroscopy (VPD-TXRF), VPD/inductively coupled plasma-mass spectrometry (VPD/ICP-MS). SEMI, San Jose, [19] SEMI E46-95:1995, Specification for the determination of organic contamination from mini- environments. SEMI, San Jose, California, USA

  1. To be published. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 58 --- ISO 14644-7:2004(E) © ISO 2004 – All rights reserved

[20] SEMI E62-0701:2001, Provisional specification for 300-mm front-opening interface mechanical standard (FIMS). SEMI, San Jose, California, USA [21] SEMI S11-1296:1996, Environmental, safety and health guidelines for semiconductor manufacturing equipment minienvironments. SEMI, San Jose, California, USA [22] TC 233/N229 DS:1995, Safe biotechnology — Performance criteria for safety cabinets. CEN, Brussels, Belgium [23] A guide to hazard and operability studies. Chemical Industry and Health Council of the Chemical Industry Association, Publications Department,1977, London, UK [24] COLES, T. Isolation technology: A practical guide. Interpharm Press, 1998, Buffalo Grove, Illinois, USA [25] FULTON, S., BASS, E. and CHRISTAL, L. I300I Factory Guideline Compliance: Factory Integration Maturity Assessment for 300 mm Production Equipment: Version 4.0. International Sematech Technology Transfer # 98023468B-TR, March 31, 1999, Appendix G, Minienvironment Parametric Test Methods. International Sematech, 1999, Austin, Texas, USA [26] Isolators for pharmaceutical applications, ISBN 0 11 701829 5. HMSO, 1994, London, UK [27] SHERWOOD, E., HOPE, D., WHITMORE, J., OTTESEN, C. and DAVIS, C. Integrated Minienvironment Design Best Practices. International Sematech Technology Transfer # 99033693A, March 31, 1999, International Sematech, 1999, Austin, Texas, USA [28] SIRCH, E.C. Isolatortechnik in der pharmazeutischen Industrie, in: Reinraumtechnik, Gail, L. and Hortag, H.P. (eds.), pp. 168-211, Springer Verlag, 2001, Berlin-Heidelberg-New York [29] SIRCH, E.C. User requirements and design specifications of isolator containment for pharmaceutical production, in: 1998 Proceedings of the 44th Annual Technical Meeting of the IEST concurrent with the ICCCS 14th International Symposium on Contamination Control, p. 343, Institute of Environmental Sciences and Technology, Phoenix, Arizona, USA [30] TOLLIVER, D.L. (ed.). Handbook of contamination control in microelectronics: principles, applications and technology. Noyes Publications, 1988, Park Ridge, New Jersey, USA [31] WAGNER, C.M. and AKERS, J.E. (eds.). Isolator technology: applications in the pharmaceutical and biotechnology industries. Interpharm Press, 1995, Buffalo Grove, Illinois, USA

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 59 --- Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

--- PAGE 60 --- ISO 14644-7:2004(E) ICS 13.040.35 Price based on 52 pages © ISO 2004 – All rights reserved

Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly Not for Resale, 10/14/2019 19:24:11 MDT No reproduction or networking permitted without license from IHS --`,,,,,,,,,,,,,,,,```,--,,,,,,,---

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