How Part 11 Compliance Impacts QbD

By John Avellanet, Cerulean Associates LLC An ominous shift in regulatory enforcement expectations is increasingly apparent to many pharmaceutical and life sciences executives around the world. The rise in the U.S. Food and Drug Administration’s (FDA) information integrity-based audit findings, 483s and warning letters reflects a larger move away from reactive post-market inspections. Interestingly, FDA officials advocate Quality by Design (QbD) as their goal, but it is hard to see the relationship between QbD and data integrity without stepping back to look at the big picture. Over the past two years, pilot programs have shown an increased approval speed for new products drawing on elements of Quality by Design. Despite this progress, the largest question remains: given that so many FDAregulated firms view their preclinical product development process as ?outside the box? of FDA regulatory oversight, how do companies intend to bring their R&D test data, laboratory results, protocols, lab notebooks, engineering prototypes and schematics into a state of compliance with QbD principles? When seen as part of the larger FDA regulatory landscape, the answer emerges from 21 Code of Federal Regulations Part 11 (21 CFR Part 11), the electronic signatures and records act. As counterintuitive as this may seem, my experience with clients over the past few years has shown that a strategic, risk-based approach to Part 11 dovetails with QbD to improve a company’s new product pipeline, speed its new product time-to-market and increase its compliance flexibility. The fact that FDA enforcement actions increasingly focus on pre-market data integrity would seem to support this. How then are Part 11 and QbD intertwined, and what are the pitfalls associated with an integrated approach? QbD discussions began within FDA during the 1990s. The idea of using QbD to speed time-to-market coalesced later, around 2003-2004, when FDA was under pressure to hasten