The Title 21 Code of Federal Regulations Part 11 (21 CFR Part 11) provides compliance information regarding the U.S. Food and Drug Administration’s (FDA) guidelines on electronic records and electronic signatures. Within this part, requirements are created to help ensure security, integrity, and confidentially of electronic records and to ensure electronic signatures are as legally binding as hand-written signatures.
Part 11 requires drug makers, medical device manufacturers, biotech companies, biologics developers, CROs, and other FDA-regulated industries, with some specific exceptions, to implement controls, including audits, system validations, audit trails, electronic signatures, and documentation for software and systems involved in processing electronic data that are
- required to be maintained by the FDA predicate rules or
- used to demonstrate compliance to a predicate rule.
A predicate rule is any requirement set forth in the Federal Food, Drug and Cosmetic Act, the Public Health Service Act, or any FDA regulation other than Part 11 [icon name=icon-external-link].
Key Concepts About 21 CFR Part 11, Electronic Records and Signatures
- When you automate collection, processing, and analysis of research information, you are creating an electronic record. 21 CFR Part 11 exists to give the agency assurance that electronic records are the same as paper records.
- When you automate the process of an individual authorizing an action, you have created an electronic signature. In addition to the controls required for electronic records, 21 CFR Part 11 contains requirements to assure the agency that electronic signatures are the legally binding equivalent of a person’s handwritten signature.
- Access control determines whether a system is open or closed. If the persons responsible for the content of electronic records also have control of system access, the system is ‘closed’. If the persons responsible for content of electronic records do not have control of system access, the system is ‘open’. Open systems require the added assurance that records are protected from point of creation to receipt.
- You can use electronic records in lieu of paper records with one caveat – only a subset of records required for pre-market approval are accepted by the agency. Accepted documents are listed in public docket No. 92S-0251. All other records required to be kept, but not submitted, can be in electronic form. In all cases, to be valid, you must comply with 21 CFR Part 11.
- Track activities and define your needs; employ a combination of procedural and technical controls for development and operation of the system; verify and certify that everything works; and document what you’ve done.
- Validation effort for medical device software must be commensurate with the level of concern for the device. There are three levels of concern:
Major – operation could result in death or serious injury
Moderate – operation could result in non-serious injury
Minor – operation not expected to result in any injury [icon name=icon-external-link]
History of 21 CFR Part 11 Development
21 Code of Federal Regulations (CFR) Part 11 has been discussed at length in the pharmaceutical industry over the past years, within the companies as well as in working groups across company borders, industry associations, seminars, and conferences. 21 CFR Part 11 was originally developed on the basis of industry request. Owing to the increased use of electronic means in the pharmaceutical industry, companies wanted to move away from paper and toward electronic systems. This included a wish to be able to replace traditional paper signatures by electronic equivalents. Based on this request, work on a regulation covering the aspects started in the early 1990s, and the final rule came out on August 20, 1997. The final rule contains the text of the law itself and a Preamble consisting of a summary of industry comments to the draft document and the Food and Drug Administration (FDA) answers to those comments. The Preamble is intended as a support in interpreting Part 11. The regulation does not only cover the use of electronic signatures, but also the requirements concerning the use of electronic records where no signatures are included [icon name=icon-external-link].
Is 21 CFR Part 11 relevant to your organization?
A US-based or international life science company must comply with 21 CFR part 11 under the following circumstances: 1) the company markets or is planning to market its product(s) in the United States, or supports any domestic or international life science company(ies) that markets or is planning to market its product(s) in the United States and 2) any of the following scenarios apply:
- Records that are required to be maintained under predicate rule requirements will be maintained in electronic format in place of paper format;
- Records that are required to be maintained under predicate rules will be maintained in electronic format in addition to paper format, and the electronic records are relied on to perform regulated activities;
- Records that are submitted to FDA, under predicate rules (even if such records are not specifically identified in Agency regulations), in electronic format (assuming the records have been identified as the types of submissions the Agency accepts in electronic format);
- Electronic signatures are intended to be the equivalent of handwritten signatures, initials, and/or other general signings required by predicate rules. 21 CFR part 11 signatures include electronic signatures that are used, for example, to document the fact that certain events or actions occurred in accordance with applicable predicate rules (e.g. approval, review, and verification).
Benefits of 21 CFR part 11 implementation
If implemented correctly, 21 CFR part 11 can help to:
- Ensure the protection and ready retrieval of electronic records
- Ensure operational consistency across all departments
- Improve productivity and efficiency of existing staff through automation
- Minimize and possibly eliminate the maintenance and retention of paper documentation
- Meet study timelines
- Perform faster study-related searches and establish trends
- Provide study-related submission information in formats acceptable to the FDA [icon name=icon-external-link]