What is 21 CFR Part 11 Compliance and Regulations

(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.

The purpose of Part 11 is to ensure electronic records and electronic signatures are as trustworthy as paper records and ink signatures.

(b) This part applies to electronic records created, modified, maintained, archived, retrieved, or transmitted under any record requirement 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 explicitly identified in agency regulations. However, this part does not apply to paper records that are, or have been, transmitted electronically.

All electronic records used for regulated purposes are subject to Part 11.                                                            One clarification: paper records transmitted electronically (e.g., as email attachments) are not subject to Part 11.

(c) When electronic signatures and their associated electronic records meet the requirements of this part, the agency will consider electronic signatures to be equivalent to full handwritten signatures, initials, and other general signings required by agency regulations, unless explicitly excepted by regulation effective on or after August 20, 1997.

If an organization can demonstrate (typically through computer system validation) that its electronic signatures comply with Part 11, the FDA will accept electronic signatures in place of ink signatures.                                                            One exception: if another regulation explicitly requires ink, that regulation supersedes Part 11.

(d) Electronic records that meet the requirements of this part may be used in lieu of paper records under § 11.2 unless otherwise explicitly required.

If an organization can demonstrate that its electronic records comply with Part 11, the FDA will accept electronic records in place of paper records.                                                            One exception: if another regulation explicitly requires paper, that regulation supersedes Part 11.

(e) Computer systems (including hardware and software), controls, and associated documentation maintained under this part shall be readily available for, and subject to, FDA inspection.

The documentation required in (c) and (d) above must be maintained in a manner accessible for FDA inspection (i.e., documentation is critical).

(f) This part does not apply to records required to be established or maintained under §§ 1.326 through 1.368 of this chapter. Records that satisfy the requirements of Subpart J of Part 1 of this chapter, and those required by other applicable statutory provisions or regulations, remain subject to this part.

A few obscure record types are excluded from Part 11 because they fall under other regulations, but the vast majority require compliance.

(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.

For regulated records not submitted to the FDA, organizations may use electronic records instead (or in addition to) paper records, provided they can demonstrate compliance with Part 11.

(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 portions of a document to be submitted have been identified in Public Docket No. 92S-0251 as a type of submission the agency accepts in electronic form. That docket will specify specifically which types of documents or portions of documents may be submitted electronically without paper records, and the agency receiving units (e.g., specific centers, offices, divisions, branches) to which such submissions may be made. Documents to agency receiving units not specified in the public docket will not be considered official if submitted electronically; the paper form of such documents will be considered official, and must be provided along with any electronic record. Consult the intended agency receiving unit for detailed information on how (e.g., transmission method, media, file format, and technical protocol) and whether to proceed with electronic submission.

For regulated records submitted to the FDA, organizations may use electronic records instead of paper if both conditions are met:                              1. They can demonstrate compliance with Part 11.                              2. The FDA accepts those record types electronically, as listed in Public Docket No. 92S-0251.                                                            If in doubt whether a record can be submitted electronically, contact the FDA receiving unit before attempting submission.

(a) The definitions and interpretations of terms contained in section 201 of the Act apply to those terms when used in this part.

Certain terms defined in the Federal Food, Drug, and Cosmetic Act also apply to Part 11.

(b) The following definitions of terms also apply to this part:

The following are key terms and their definitions:

(1) Act means the Federal Food, Drug, and Cosmetic Act (sections 201–903 (21 U.S.C. 321–393)).

Act: Short for the Federal Food, Drug, and Cosmetic Act.

(2) Agency means the Food and Drug Administration.

Agency: Short for the FDA.

(3) Biometrics means a method of verifying an individual’s identity based on measurement of the individual’s physical characteristics or repeatable actions where those characteristics and/or actions are both unique to that individual and measurable.

Biometrics: A method of verifying someone’s identity using unique physical traits (e.g., fingerprints) or repeatable actions (e.g., typing pattern).

(4) Closed system means an environment in which system access is controlled by persons who are responsible for the content of electronic records on the system.

Closed system: A computer system where user access is controlled by the same persons responsible for its content.

(5) 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.

Digital signature: An electronic signature that includes methods to verify the signer’s identity, signature validity, and the integrity of the signed record.

(6) 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.

Electronic record: Information in digital form created or handled by a computer system.

(7) 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.

Electronic signature: A set of symbols, unique and legally binding like a handwritten signature, used to sign records within a computer system.

(8) Handwritten signature means the scripted name or legal mark of an individual handwritten and executed or adopted by that individual with the intention of authenticating a writing in a permanent 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.

Handwritten signature: A scripted name or legal mark created by an individual, unique to that person, used to authenticate something in writing.

(9) Open system means an environment in which system access is not controlled by persons who are responsible for the content of electronic records on the system.

Open system: A computer system where user access is not controlled by the same persons responsible for its content.

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, 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:

Organizations using electronic records must document procedures and controls to ensure their electronic records have these qualities:                              • Authenticity                              • Integrity                              • Confidentiality (when appropriate)                              • Non-repudiation (i.e., inability to deny the record is genuine)                                                            Procedures and controls must address:

(a) Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.

Validation: How the organization proves (to itself and auditors) that data in the computer system is trustworthy.

(b) 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. Persons should contact the agency if there are any questions regarding the ability of the agency to perform such review and copying of the electronic records.

Record presentation: Ensuring all electronic records that auditors may want to view and/or copy are available in a human‑understandable format.

(c) Protection of records to enable their accurate and ready retrieval throughout the records retention period.

Document storage and retention: How the organization safeguards records and keeps them readily available during the required retention period.

(d) Limiting system access to authorized individuals.

System access: Ensuring only appropriate personnel can access each computer system.

(e) Use of 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.

Audit trail: Ensuring the computer system automatically captures the full history of electronic records, retains them for the appropriate time, and makes them available for human review.

(f) Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.

Workflow: Ensuring electronic workflows in the system function properly.

(g) Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the system input or output devices, modify a record, or perform the operation at hand.

Authority checks: Restricting user access (system‑level and record‑level) and verifying users performing functions are authorized.

(h) Use of device (e.g., terminal) checks to determine, as appropriate, the validity of the source of data input or operational instructions.

Device checks: Verifying that equipment used for regulated purposes operates correctly.

(i) Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks.

Personnel qualification: Ensuring only trained and qualified personnel perform functions within or on the system.

(j) The establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification.

Personnel accountability: Holding individuals responsible for the integrity of their actions related to electronic records and signatures.

(k) 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 documents time-sequenced development and modification of systems documentation.

Documentation control: Controlling documents related to system operation and maintenance, and preserving a complete history of changes to those documents.

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, confidentiality of electronic records from the point of creation to the point of receipt. Such procedures and controls shall include those identified in § 11.10, as appropriate, and additional measures such as document encryption and use of appropriate digital signature standards to ensure, as necessary under the circumstances, record authenticity, integrity, and confidentiality.

For organizations using open systems, all requirements for closed systems (§ 11.10) still apply. In addition, they must take extra steps (the most meaningful given risk and available options) to ensure the same record qualities described in § 11.10:                              • Authenticity                              • Integrity                              • Confidentiality (when appropriate)                              • Non-repudiation                                                            *A computer system where user access is not controlled by those responsible for content.

(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 of the signature; and                              (3) The meaning of the signature (e.g., review, approval, responsibility, or authorship).

Whenever an electronic record is signed, the following must be visible and linked to the signature:                              • Signer’s printed name                              • Date and time of signing                              • Meaning of the signature (e.g., content verified, approved, accurate)

(b) The items identified in paragraphs (a)(1), (a)(2), and (a)(3) of this section shall be subject to the same controls as electronic records and shall be included as part of any human readable form of the electronic record (such as electronic display or printout).

The three data items above are also subject to Part 11 and must be in human-readable format.

Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective electronic records to ensure that the signatures cannot be copied, transferred, or otherwise used to falsify electronic records by ordinary means.

Any type of signature (handwritten or electronic) applied to an electronic record must remain permanently linked to that record. It cannot be removed, overwritten, erased, transferred, etc.

(a) Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.

Each person must have a unique electronic signature, never used by anyone else before or after.

(b) Before an organization establishes, assigns, certifies, or otherwise approves an individual’s electronic signature, or any element of such electronic signature, the organization shall verify the individual’s identity.

Before someone may use an electronic signature, his/her identity must be verified.

(c) Persons using electronic signatures shall, prior to or at the time of such use, certify to the agency that the electronic signatures in their system, used on or after August 20, 1997, are intended to be the legally binding equivalent of traditional handwritten signatures.                                                            (1) The certification shall be submitted in paper form and signed with a traditional handwritten signature, to the Office of Regional Operations (HFC-100), 5600 Fishers Lane, Rockville, MD 20857.                                                            Persons using electronic signatures shall, upon agency request, provide additional certification or testimony that a specific electronic signature is the legally binding equivalent of the signer’s handwritten signature.

Before implementing electronic signatures, an organization must notify the FDA in writing and state it intends for electronic signatures to be legally binding equivalents of ink signatures.                                                            The first step is a paper letter, ink‑signed and mailed to the FDA.                                                            If the FDA requests additional evidence that the organization treats electronic signatures as legally binding, the organization must provide it.

(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.                              (i) When an individual executes a series of signatures during a single, continuous controlled system access, the first signature shall be executed using all electronic signature components; subsequent signatures shall be executed using at least one electronic signature component that is only executable by, and designed for use only by, the individual.                              (ii) When an individual executes one or more signatures not performed during a single, continuous controlled system access, each signature shall be executed using all electronic signature components.                              (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.

Non‑biometric electronic signatures (not based on physical traits like fingerprints) must:                              • Consist of at least two distinct parts (i.e., user ID and password).                              • For the first signature after login: require all components.                              • For subsequent signatures in the same session: require at least one component (e.g., password).                              • After logout or timeout: full components are required again.                              • Be usable only by the assigned individual.                              • Require collaboration of two or more people if someone other than the owner must use it (e.g., system admin + supervisor, only when the signer is unavailable).

(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 (e.g., fingerprint scan, retinal scan) may only be used by the assigned individual.

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:

For electronic signatures using identification codes (user IDs) and passwords, the following controls are required:

(a) Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same identification code and password combination.

No two users may share the same user ID + password combination; each must be unique, and each user ID assigned to only one person.

(b) Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover password aging events).

Passwords must be periodically checked, revoked, or changed.

(c) Following loss management procedures to electronically deauthorize 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.

If password tokens/devices are lost or stolen, authorization must be revoked and secure replacements issued.

(d) Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and to detect and report immediately and urgently any attempts at unauthorized use of passwords and/or identification codes to the system security unit, and organization management as appropriate.

Unauthorized access attempts to user IDs or passwords must be detected and reported to the appropriate team for investigation.

(e) Initial and periodic testing of devices that bear or generate identification code or password information to ensure that they function properly and have not been altered in an unauthorized manner.

Password tokens must be tested before issuance and periodically during use to ensure proper function and no unauthorized modification.