FDA plans to amend 21 CFR Part 11 rules

The US Food and Drug Administration has issued its final guidance document describing its current thinking regarding the scope and application of 21 CFR Part 11 on electronic records and electronic signatures. The FDA is re-examining Part 11 as it applies to all FDA regulated products, and said it anticipates initiating rulemaking to change the regulation as a result of that re-examination. This is part of its overall cGMP initiative Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach . The final guidance explains how the agency will narrowly interpret the scope of Part 11. While the re-examination is under way, it intends to exercise enforcement discretion with respect to certain Part 11 requirements, i.e. it will not take enforcement action to enforce compliance with the validation, audit trail, record retention and record copying requirements of the regulation. The new guidance on electronic records is just one of a series of new initiatives announced by the FDA on the first anniversary of its cGMP initiative. The others include: a draft guidance on a process for resolving disputes arising over scientific and technical issues related to pharmaceutical cGMP; a draft guidance on the aseptic processes used in the manufacture of sterile drugs, emphasizing current science and risk-based approaches; a draft guidance on preparation and use of a comparability protocol for assessing chemistry, manufacturing and control changes to protein drug products and biological products; and a draft guidance for Process Analytical Technology (PAT) - a framework for allowing regulatory processes to more readily adopt state-of-the-art technological advances in drug development, production and quality assurance. "All of the major steps announced today are part of our programme to increase efficiencies while maintaining and enhancing FDA's high standards for safety in our regulation of the manufacturing of human drugs and biologics and veterinary drugs," said FDA Commissioner Mark McClellan. The agency has also set up a new Pharmaceutical Inspectorate, resulting from a collaboration between the Office of Regulatory Affairs and the Center for Drug Evaluation and Research, which will operate a team dedicated to conducting human drug manufacturing quality inspections on the majority of prescription drug manufacturers and other complex or high risk pharmaceutical operations. The PI will also conduct pre-approval inspections and may conduct or assist in investigations that would benefit from its expertise. Other measures announced by the FDA include a collaboration with Georgetown and Washington Universities to identify the factors that predict manufacturing performance in a bid to "further refine our pharmaceutical manufacturing risk-based assessment," according to the agency. Meanwhile, it will be working with the National Science Foundation's Center for Pharmaceutical Processing Research to expand its scientific foundation in the area of innovative pharmaceutical manufacturing technology, and implementing a programme with Pfizer to research chemical imaging applications in pharmaceutical manufacturing and quality assurance. The ISPE commented that the new Part 11 guidance suggests that the FDA does not intend to take action to enforce any Part 11 requirements with regard to systems that were operational before the effective date of the regulation, as long as certain criteria defined in the guidance are met, according to the International Society of Pharmaceutical Engineering. Despite this pull-back from enforcement, the agency stresses that Part 11 remains in effect and records must still be maintained or submitted in accordance with the underlying predicate rules. It will still take regulatory action for non-compliance with these principles rules, ie the underlying requirements set forth in the regulation, as well as the Public Health Service Act and other FDA regulations. A number of comments received regarding the February 2003 draft version of the guidance have been addressed in the final version, notes the ISPE. The changes include clarification of enforcement discretion in general (and particularly with regard to legacy systems), clarification of the FDA's position on time stamps, and a statement that the agency does not intend to re-issue the withdrawn Part 11 draft guidance documents.