21 CFR PART 11 — ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Source: eCFR / Cornell LII (current through April 2026) URL: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-11
21 CFR Part 11 was promulgated by the FDA in 1997 (62 FR 13430) and establishes criteria under which the agency considers electronic records and electronic signatures trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper. It applies to all FDA-regulated industries: pharmaceuticals, biologics, medical devices, food, cosmetics, and tobacco.
The regulation responds to the rapid adoption of computerized systems in regulated industries during the 1990s. Before Part 11, no clear federal standard existed for the acceptability of electronic records as alternatives to paper records required by FDA regulations.
FDA 2003 GUIDANCE ON SCOPE AND APPLICATION In August 2003, FDA issued a guidance document "21 CFR Part 11; Electronic Records; Electronic Signatures — Scope and Application" which significantly narrowed the agency's enforcement focus. Key points:
PREDICATE RULE CONCEPT: Part 11 applies only to electronic records that FDA regulations require to be maintained or submitted and where the regulated entity chooses to use electronic records instead of paper records. The underlying FDA regulation requiring the record is called the "predicate rule" (e.g., 21 CFR 211.68 — computers in drug manufacturing; 21 CFR 211.186 — master production and control records; 21 CFR 211.188 — batch production records).
ENFORCEMENT DISCRETION: FDA exercises enforcement discretion regarding certain Part 11 requirements for:
WHAT PART 11 DOES NOT REQUIRE: Part 11 does NOT mandate that any entity use electronic records or electronic signatures. It only governs the standards IF electronic records/signatures are used.
RISK-BASED APPROACH: FDA encourages a risk-based approach to Part 11 compliance. Not all predicate rule records carry equal risk. The investment in controls should be commensurate with the risk to product quality and patient safety.
PART 11 AND ALCOA+ Part 11's requirements align directly with ALCOA+ data integrity principles:
The "+" elements (Complete, Consistent, Enduring, Available) are addressed by:
CDMO RELEVANCE In a pharmaceutical CDMO context, Part 11 applies to:
§ 11.1 SCOPE
(a) The regulations in this part set forth the criteria under which the agency considers electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.
(b) This part applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted, under any requirements set forth in agency regulations. This part also applies to electronic records submitted to the agency under requirements of the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act, even if such records are not specifically identified in agency regulations. However, this part does not apply to paper records that are, or have been, transmitted by electronic means.
(c) Where electronic signatures and their associated electronic records meet the requirements of this part, the agency will consider the electronic signatures to be equivalent to full handwritten signatures, initials, and other general signings as required by agency regulations, unless specifically excepted by regulation(s) effective on or after August 20, 1997.
(d) Electronic records that meet the requirements of this part may be used in lieu of paper records, in accordance with § 11.2, unless paper records are specifically required.
(e) Computer systems (including hardware and software), controls, and attendant documentation maintained under this part shall be readily available for, and subject to, FDA inspection.
KEY INTERPRETATION: §11.1 does not apply to paper records simply transmitted electronically (e.g., a scanned PDF of a paper record sent by email). The electronic record must itself be created, modified, maintained, or archived in electronic form.
§ 11.2 IMPLEMENTATION
(a) For records required to be maintained but not submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that the requirements of this part are met.
(b) For records submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that: (1) The requirements of this part are met; and (2) The document or parts of a document to be submitted have been identified in public docket No. 92S-0251 as being the type of submission the agency accepts in electronic form. This docket will identify specifically what types of documents or parts of documents are acceptable for electronic submission. The agency will periodically publish in the Federal Register a list of the types of documents it will accept electronically.
§ 11.3 DEFINITIONS
As used in this part:
(a) Act means the Federal Food, Drug, and Cosmetic Act (sec. 201-903 of the act (21 U.S.C. 321-394)).
(b) Agency means the Food and Drug Administration.
(c) Biometric means a method of verifying an individual's identity based on measurement of the individual's physical feature(s) or repeatable action(s) where those features and/or actions are both unique to that individual and measurable.
(d) Closed system means an environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system.
EXAMPLE: A dedicated pharmaceutical manufacturing control system (DCS/SCADA) where only authorized company personnel can access and whose access is managed by the company's IT/quality team is a closed system. The company controls both who can log in and what records are stored.
(e) Digital signature means an electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified.
NOTE: Digital signatures (using cryptography like RSA or ECDSA) are a SUBSET of electronic signatures. Not all electronic signatures are digital signatures. PKI-based systems use digital signatures.
(f) Electronic record means any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
(g) Electronic signature means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature.
(h) Handwritten signature means the scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in an electronic form. The act of signing with a writing or marking instrument such as a pen or stylus is preserved. The scripted name or legal mark, while conventionally applied to paper, may also be applied to other devices that capture the name or mark.
(i) Open system means an environment in which system access is not controlled by persons who are responsible for the content of electronic records that are on the system.
EXAMPLE: A cloud-based system accessed over the public internet, or a third-party hosted system where the cloud provider (not the pharmaceutical company) controls system access, is an open system. Email systems are open systems. Systems accessed via public telecommunication infrastructure are open systems.
OPEN vs CLOSED SYSTEM KEY DISTINCTION: The determining factor is NOT the technology (internet vs intranet) but WHO controls access. If the persons responsible for the electronic records control system access → CLOSED. If access is controlled by others →OPEN.
§ 11.10 CONTROLS FOR CLOSED SYSTEMS
Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, when appropriate, the confidentiality of electronic records, and to ensure that the signer cannot readily repudiate the signed record as not genuine. Such procedures and controls shall include the following:
(a) VALIDATION Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.
Validation Scope: This encompasses Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ). The depth of validation should be commensurate with risk. Systems that create, modify, or maintain records that support product release decisions require rigorous validation.
FDA 2003 Guidance interpretation: For legacy systems (predating August 1997), FDA exercises enforcement discretion on validation requirements provided the system otherwise meets Part 11. New systems must be fully validated.
Computer System Validation (CSV) requirements under §11.10(a):
(b) READABLE COPIES The ability to generate accurate and complete copies of records in both human readable and electronic form suitable for inspection, review, and copying by the agency.
This requirement ensures that if FDA inspectors arrive on-site, they can receive complete, accurate, human-readable copies of all electronic records. Systems must export records to formats accessible to the agency (PDF, CSV, printed copies). Data migration to new systems must preserve readability of archived records.
(c) PROTECTION OF RECORDS Protection of records to enable their accurate and ready retrieval throughout the records retention period.
Records must be protected from:
Retention periods are defined by predicate rules (e.g., 21 CFR 211.180 — drug records must be retained at least 1 year after drug expiry, typically 2-3 years minimum for most pharmaceutical records, up to lifetime for biologics).
(d) LIMITING SYSTEM ACCESS Limiting system access to authorized individuals.
Access controls implementation:
The prohibition on shared accounts is a common FDA 483 observation: "Shared usernames/passwords observed in [LIMS/DCS/eBR system]."
(e) AUDIT TRAILS Secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Record changes shall not obscure previously recorded information. Such audit trail documentation shall be retained for a period at least as long as that required for the subject electronic records and shall be available for agency review and copying.
CRITICAL ELEMENTS OF §11.10(e) AUDIT TRAILS:
COMMON AUDIT TRAIL DEFICIENCIES (FDA 483 OBSERVATIONS):
(f) OPERATIONAL SYSTEM CHECKS Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.
This controls the workflow sequence in electronic systems. For example:
(g) AUTHORITY CHECKS Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at issue.
Authority checks go beyond access controls (§11.10d) to specifically govern:
(h) DEVICE CHECKS Use of device checks to determine, as appropriate, the validity of the source of data input or operational instruction.
Device checks ensure that:
(i) EDUCATION, TRAINING AND EXPERIENCE Determination that persons who develop, maintain, or use electronic record/ electronic signature systems have the education, training, and experience to perform their assigned tasks.
This mirrors 21 CFR 211.68 training requirements but specifically for computer systems. Training must be:
(j) WRITTEN POLICIES The establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures.
This creates the legal/administrative framework ensuring that electronic signatures carry the same accountability weight as handwritten signatures. SOPs must:
(k) USE OF APPROPRIATE CONTROLS FOR SYSTEMS DOCUMENTATION Use of appropriate controls over systems documentation including: (1) Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance. (2) Revision and change control procedures to maintain an audit trail that identifies the date of, and the nature of, changes to systems documentation, and the individuals making the change.
Systems documentation includes:
These documents must be controlled under the company's document management system (DMS), itself typically a Part 11 compliant system.
§ 11.30 CONTROLS FOR OPEN SYSTEMS
Persons who use open systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, as appropriate, the confidentiality of electronic records from the point of their creation to the point of their receipt.
Open systems require ALL controls in §11.10 PLUS additional safeguards:
WHY OPEN SYSTEMS NEED MORE CONTROLS: In a closed system, the company controls who has access — physical and logical access controls are sufficient. In an open system (accessible via public networks), records can be intercepted during transmission. Encryption protects confidentiality. Digital signatures protect integrity (any alteration of the transmitted record would invalidate the digital signature).
PRACTICAL EXAMPLE: A CRO submitting clinical data to a sponsor via a cloud platform. The CRO cannot fully control access to the cloud infrastructure (managed by AWS, Azure, etc.) — this is an open system. The data submission must be encrypted and digitally signed to meet §11.30.
§ 11.50 SIGNATURE MANIFESTATIONS
(a) Signed electronic records shall contain information associated with the signing that clearly indicates all of the following: (1) The printed name of the signer; (2) The date and time when the signature was executed; and (3) The meaning (such as review, approval, responsibility, or authorship) associated with the signature.
(b) The items identified in paragraphs (a)(1), (a)(2), and (a)(3) of this section shall be subject to the same controls as for electronic records and shall be included as part of any human readable form of the electronic record (such as electronic display or printout).
THREE MANDATORY ELEMENTS OF §11.50 SIGNATURE MANIFESTATIONS:
COMMON DEFICIENCIES:
§ 11.70 SIGNATURE/RECORD LINKING
Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective electronic records to ensure that the signatures cannot be excised, copied, or otherwise transferred to falsify an electronic record by ordinary means.
ANTI-FALSIFICATION PURPOSE: §11.70 prevents what is called "signature cut-and-paste" fraud: extracting a valid electronic signature from a legitimate record and inserting it into a falsified record. Technical implementations include:
FDA INSPECTION FOCUS: Inspectors may test this by asking: "If I print this batch record, can the signature block be cut and pasted into another document?" The system design must make this technically impossible or detectable.
§ 11.100 GENERAL REQUIREMENTS FOR ELECTRONIC SIGNATURES
(a) Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.
UNIQUENESS PRINCIPLE: One electronic signature (the combination of user ID, password, and/or biometric) maps to exactly one person. No sharing, no delegation. This is why shared accounts are fundamentally incompatible with Part 11 — if two people share an ID/password, the signature is not unique to one individual.
(b) Before an organization establishes, assigns, certifies, or otherwise sanctions an individual's electronic signature, or any element of such electronic signature, the organization shall verify the identity of the individual.
IDENTITY VERIFICATION: The company must verify who a person is before assigning them an electronic signature. Acceptable methods:
This requirement means "provisioning" an account requires documented identity verification — not just completing a form.
(c) Persons using electronic signatures shall, prior to or at the time of such use, certify to the agency in writing that the electronic signatures in their system are intended to be the legally binding equivalent of traditional handwritten signatures. Upon agency request, such certification shall be submitted in paper form with a traditional signature to the docket established by the agency for such purposes.
FDA LETTER REQUIREMENT: §11.100(c) requires companies to submit a letter to FDA certifying that their electronic signatures are legally binding equivalents of handwritten signatures. This is typically a one-time submission per company (not per system or per user), sent to: FDA Office of Regional Operations (ORO), Docket No. 92S-0251.
(d) If an individual is using electronic signatures in a way not in compliance with this paragraph, the electronic signature is not considered to be the equivalent of a traditional handwritten signature.
§ 11.200 ELECTRONIC SIGNATURE COMPONENTS AND CONTROLS
(a) Electronic signatures that are not based upon biometrics shall: (1) Employ at least two distinct identification components such as an identification code and password.
(2) Be used only by their genuine owners; and
(3) Be administered and executed to ensure that attempted use of an individual's electronic signature by anyone other than its genuine owner requires collaboration of two or more individuals.
WHEN BOTH COMPONENTS ARE REQUIRED (NON-BIOMETRIC):
PRACTICAL IMPLEMENTATION:
(b) Electronic signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than their genuine owners.
BIOMETRIC ELECTRONIC SIGNATURES: Biometrics (fingerprint, retinal scan, facial recognition, voice recognition) are inherently individual — you cannot transfer your fingerprint to another person. Therefore, the two-component requirement of (a) does not apply to biometric signatures. Instead, the system design must ensure:
§ 11.300 CONTROLS FOR IDENTIFICATION CODES/PASSWORDS
Persons who use electronic signatures based upon use of identification codes in combination with passwords shall employ controls to ensure their security and integrity. Such controls shall include:
(a) Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password.
(b) Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging, with appropriate token revisions as necessary).
PASSWORD MANAGEMENT REQUIREMENTS:
(c) Following loss management procedures to electronically de-authorize lost, stolen, missing, or otherwise potentially compromised tokens, cards, and other devices that bear or generate identification code or password information, and to issue temporary or permanent replacements using suitable, rigorous controls.
LOST/STOLEN CREDENTIAL RESPONSE:
(d) Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and to detect and report in an immediate and urgent manner any attempts at their unauthorized use to the system security unit, and, as appropriate, to organizational management.
TRANSACTION SAFEGUARDS:
(e) Initial and periodic testing of devices, such as tokens or cards, that bear or generate identification code or password information to ensure that they function properly and have not been altered in a unauthorized manner.
TOKEN/DEVICE TESTING: For systems using hardware tokens (RSA SecurID, smart cards, USB security keys), these devices must be:
PREDICATE RULES — KEY CROSS-REFERENCES:
21 CFR 211.68 (Automatic, Mechanical, and Electronic Equipment):
21 CFR 211.186 (Master Production and Control Records):
21 CFR 211.188 (Batch Production and Control Records):
21 CFR 211.194 (Laboratory Records):
21 CFR 211.180 (General Requirements for Records and Reports):
§11.10(a) requires validation but does not define the validation methodology. Industry has adopted the GAMP 5 (Good Automated Manufacturing Practice) framework published by ISPE:
GAMP 5 CATEGORIES OF SOFTWARE:
CSV LIFECYCLE DOCUMENTS FOR PART 11 COMPLIANCE:
CRITICAL VALIDATION REQUIREMENTS FOR PART 11 SYSTEMS:
TYPICAL FDA INSPECTION QUESTIONS FOR PART 11:
"Show me your audit trail for this batch record"
"Who has administrator access to this system?"
"Can you generate a complete copy of this batch record for me?"
"What is your process when an employee leaves the company?"
"Show me the validation documentation for this system"
"What is your SOD [Separation of Duties] for this system?"
"Show me your password policy and password reset procedure"
COMMON PART 11 FDA 483 OBSERVATIONS (REAL EXAMPLES):
Q: Does Part 11 require electronic records? A: NO. Part 11 only applies if a company CHOOSES to use electronic records for records that predicate rules require to be maintained.
Q: Does Part 11 apply to ALL computer systems? A: NO. Only to systems that CREATE, MODIFY, MAINTAIN, ARCHIVE, RETRIEVE, or TRANSMIT records required by predicate FDA regulations. A general purpose email system used for non-regulated communications is not a Part 11 system (though if used to transmit regulated records, those records and that transmission would be subject to Part 11).
Q: What is the difference between an electronic signature and a digital signature? A: Digital signatures use public key cryptography (PKI) and are a subset of electronic signatures. An electronic signature can be as simple as an ID+password combination. A digital signature is a specific cryptographic technique. Part 11 requires electronic signatures; digital signatures are required for open systems (§11.30) when additional security is needed.
Q: Can you use biometrics alone (without password) for signing? A: YES. §11.200(b) states that biometric signatures must be designed to ensure only genuine owners can use them — the two-component requirement applies only to non-biometric signatures.
Q: How long must audit trails be retained? A: At least as long as the associated electronic record (§11.10e). The retention period is set by the predicate rule for each record type.
Q: Must FDA be notified before implementing a Part 11 system? A: Only §11.100(c) requires FDA notification — a one-time written certification that electronic signatures are intended to be legally binding. This is not a per-system notification but a company-level declaration.
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