IPQ Monthly Update — May 2012 in Review

In the May Monthly Update, IPQ focuses on the GMP inspection and enforcement developments at FDA and their global impact, on the one hand, and the efforts at EMA to further refine and harmonize the European CMC expectations for clearing products for marketing, on the other.

Responding to an FDA 483 observations report under the pressure of the timelines involved is not easy and missteps can be very costly.  The lead story provides some valuable insights from a veteran field compliance official on what FDA is looking for in the response and the inspection aftermath.

The May issue also takes a look at the data integrity component of FDA’s drug enforcement program in particular.  An uptick in the number of integrity problems agency investigators are finding is prompting the drug compliance office to better define the forms that the problems take and the red flags for their occurrence.

In the third in the series, IPQ provides the agency’s latest advice on its expectations for field alert reporting – a challenging part of the compliance picture for companies to get right and one that investigators are reviewing.

Warning letters are instructive on how the tectonics of cGMP are shifting.  With its broad reach, FDA has the opportunity to watch the evolution of manufacturing controls and get a pretty clear picture of where the resistances lie that can come back to jeopardize the quality of marketed products and the health of those who rely on them. The agency uses warning letters to inform the management of a particular company when it is taking undue risks, but also to share the insights with the broader pharma community. The May issue includes two warning letter stories addressing:

● a bolus of letters that went out to foreign firms during a two-week span in late February and early March, and what they have to say on the problems FDA is finding in the API, injectable and oral OTC solution arenas, and

● the repercussions of not paying enough attention to making sure that design and technology knowledge is transferred when products are shifted from one manufacturer to another, as one big pharma warning letter recipient experienced.

The FDA enforcement coverage continues with a give-and-take among seven former FDA chief counsels on the causes, meaning, and pros and cons of the shifts in enforcement policy over the four decades their service tenures spanned. While some of the former counsels at the FDLI panel session put their emphasis on the need for more clear guidance to industry and cautioned against legal overreach, others focused on the ineffectiveness of rules and guidance that aren’t enforced.

Also provided is an analysis by a veteran manufacturing director on where the shortfalls are on the shop floor and in the company management and culture that draw companies into compliance and recall problems.

The series of three stories on the European CMC front address:

EMA’s release of a draft process validation guideline aimed primarily at explaining what reviewers want to see included in marketing applications

a finalized guideline on the quality documentation requirements for getting clinical trial approval for biological products in Europe that is the result of extensive EMA vetting with stakeholders and should help bring some harmony to what has been a disparate process, and

revised biosimilars guidelines that are nearing release and other key EMA biotech CMC initiatives, including the cooperative application review effort with FDA.

The IPQ “Updates in Brief” section provides additional coverage of: an ISPE particulate containment good practice guide; the Chinese SFDA’s overseas inspection program; a USP MoU with South Korea; and an Rx-360 supply chain security white paper.

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