Global Equivalents and Related Regulations
Global Equivalents to 21 CFR Part 11
EMEA Guidelines to Good Manufacturing Practice: Annex 11 (European Union)
Part 11 and Annex 11 provide detailed information on generating and storing electronic data generated in the course of GXP laboratory or manufacturing work. Annex 11 offers a guide to operating in a compliant GXP space, while Part 11 is a list of prohibitions, but they are largely harmonized. Notable differences include how individuals must be identified and expectations regarding personal liability for use or misuse of secure access.
ERES Guideline: Application for Approval of Licensing of Drugs (Japan)
Japanese guidelines for generating and storing electronic records closely match the intent of U.S. Part 11. Companies closely adhering to 21 CFR 11 will be in compliance with the ERES guideline, but Japanese companies will need to take precautions to fully adhere to Part 11 for products sold in the U.S.
Food & Drugs Act, Division C.02 (Canada)
Canadian regulations are written to place the responsibility for compliance on the individual where U.S. Part 11 regulations provide a series of requirements without specifically identifying responsible parties. The Canadian guidelines also account for Mutual Recognition Agreements (MRAs) with countries whose standards are of equivalent scope and depth. MRAs allow for more rapid import and approval of raw materials and finished products across borders.
Related Codes, Regulations & Guidance Documents
21 CFR provides extended guidance for application of good manufacturing practice (GMP, 21 CFR 210 and 211) and good laboratory practice (GLP, 21 CFR 58) as well as the production of biological products (biologics) including,
21 CFR 210-211: Guidelines for cGMP manufacturing, processing, packing, or holding drugs and finished pharmaceuticals
For cleanroom operators, 21 CFR Parts 210-211 underscore the importance of validated quality controls for all steps in the production workflow including air-quality monitoring. All work pertaining to the production and packaging of drugs must be conducted and recorded in compliance with written SOPs. All records pertaining to the production of a drug will be reviewed annually. As noted in Part 11, personnel engaged in drug manufacturing and packaging must have adequate and ongoing training and education to perform their assigned functions in a cGMP setting.
21 CFR 58: Guidelines for cGLP non-clinical laboratory studies
For cleanroom operators (including CROs) this guideline defines quality assurance requirements for active surveillance of compliance to SOPs and record-keeping. All data and documents generated as part of cGLP activities must be properly recorded and maintained for regular review. All records are subject to inspection by the FDA.
21 CFR 600: Guidelines for the manufacture and distribution of biologics
For cleanroom operators, 21 CFR Part 600 provides predicate guidance to 21 CFR 11 regarding records retention. All records relative to biologics manufacturing must contemporaneously capture all steps as they occur, including air-quality monitoring. The record should include who conducted the air-quality audit, the date and time of the audit and any discursions (and associated rationale) from the SOP.
PIC/S Annex 11 – PI 011-3: Good Practices for Computerised Systems in Regulated GxP Environments (2007 )
FD&C 505: Federal Food, Drug, & Cosmetic Act, Section 505, New Drugs
Any new drug submitted for approval under FD&C 505 must be supported by evidence of drug safety, strength, and activity. These analyses depend on the sterility and air quality of cleanrooms. All evidence submitted to support air quality in the manufacturing cleanroom must be supported by auditable data.
PHS 351: Public Health Service Act 351 (U.S. Code Title 42, Chapter 6A )
This act defines a biologic as any “virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product…applicable to the prevention, treatment, or cure of a disease or condition of human beings.” The act further define biosimilars as a biological product “highly similar to the reference product notwithstanding minor differences in clinically inactive components” with no effective difference in “safety, purity, and potency of the product.” While cleanroom air quality data are not specifically required for submission under this act, the act notes any “facility in which the biological product is manufactured, processed, packed, or held” must meet standards for ensuring the product’s safety and purity.
USP<787> Subvisible particulate matter in therapeutic protein injections
Due to the contamination risk presented by airborne particles to injectable therapeutics, USP<787> recommends liquid particle testing be done under controlled conditions in which airborne particles are minimized and monitored. USP<787> is an SOP for liquid particle analysis and does not provide specific guidance on electronic records requirement for environmental monitoring of air quality during liquid particulate testing.
ISO/IEC 27001:2013, International Organization for Standardization/International Electrotechnical Commission Standard on Information Security Management Systems
This international standard for information security applies to organizations and cleanroom operators who maintain their records electronically. It provides for internal auditing of processes based on a risk-management approach.
ISO 13485:2016, International Organization for Standardization Standard on Medical Devices
This international standard requires documents (electronic or otherwise) be subject to standard procedures for creation, review, change control and obsolescence. All QC records must be present in the quality management system for review.
ICH E6: International Committee on Harmonization Standard Good Clinical Practice: Consolidated Guidance
This guideline aligns with 21 CFR 11, dictating all stages of data handling—from data generation to data review and storage—be done according to defined quality controls.