Updated guidances from FDA and the Pharmaceutical Inspection Co-operation Scheme (PIC/S) on maintaining data integrity (DI) across the product lifecycle have deepened the pool of resources that industry now has available to support its DI efforts.
In December, FDA’s centers for drugs, biologics, and veterinary medicine (CDER, CBER, and CVM) released a finalized version of their guidance for industry on “Data Integrity and Compliance with Drug CGMP,” containing some substantive changes from the draft issued in 2016.
Changes to the guidance included new expectations for executive management, expansion of specific compliance activities, and clarification of language and provisions. The current version brings FDA’s guidance into alignment with the PIC/S guidance as well as those from UK’s MHRA, the Parenteral Drug Association (PDA), the International Society for Pharmaceutical Engineering (ISPE), and others in delineating the importance of “quality culture” and management’s role in establishing it. Other substantive changes to the FDA guidance were around audit trails and remediation.
The format of the FDA guidance remains the same as the draft version, with a preamble containing separate introductory and background sections, and the body consisting of 18 pairs of questions and answers. Sequentially, questions 7 and 8 were reversed. The final guidance explains who should review audit trails (previously Q8) before discussing how often it should be done (previously Q7) – elaborating further on each.
The PIC/S document, entitled “Good Practices for Data Management and Integrity in Regulatory GMP/GDP Environments,” was issued in November, and represents a third draft. Like FDA’s, the previous draft was issued in 2016.
During the comment period on the update, which closed at the end of February, PIC/S sought substantive feedback from four associations on specific questions relating to the proportionality, clarity, and implementation of the guidance requirements. The four were: ● the European Compliance Academy (ECA) ● the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) ● ISPE, and ● PDA.
Changes to the PIC/S guidance included a new section on hybrid systems, more elaboration around computerized systems and audit trails, and – similarly to the FDA guidance – more refined and specific terminology.
Like FDA’s, the PIC/S guidance retains the format, but was significantly increased from 41 to 52 pages. A new one-page section was added on hybrid systems. Another half of the new text centered around qualification and validation of computerized systems, system security, and audit trails. Expanded explanations, examples, and best practices throughout the document made up the balance of the additional length.
[Editor’s Note: See IPQ’s June/July 2016 Monthly Update for the last major IPQ foray into the DI regulatory landscape, including a review of: ● the current FDA, MHRA and WHO guidances ● industry comments on the 2016 FDA draft, and ● regulator expectations for handling DI concerns.]