PAT and QbD Have Many Benefits, but Don’t Bank on Regulatory Relief
Brian Stephens, a life sciences consultant for ABB INC, addressed the Interphex 2008 attendees this morning in a discussion about process analytical technology (PAT). He threw out the “learn, predict, control” phrase industry has latched onto as an easier way to define PAT, which is essentially a tool or system for implementing QbD that involves identifying critical quality attributes (CQAs) and critical process parameters (CPPs), and then figuring out the best way to measure the CQAs in order to control the CPPs.
Stephens went on to describe how some 60 FDA investigators are undergoing PAT training this year so they can be better prepared for inspections (and ideally avoid a repeat of the validation inspection process of the 1980s and early 1990s when computer validation came into play). (I find it quite strange, by the way, that FDA has been rolling out and pushing PAT initiatives while still learning about it themselves. Seems like the order of things here is somewhat backward.)
Anyway, Stephens’ presentation focused on the benefits of PAT which ultimately come down to a company’s return on investment. Production life cycle time might be reduced by 40%, he said, with PAT applications. Multi-instrumentation might reduce process cycle time by 50%, electronic storage of information might reduce QA costs by 15%, and yield might increase with the help of design space and getting manufacturing right “the first time.” In addition, companies might be able to save millions of dollars by implementing PAT. For example, said Stephens, a $10b company that improves its efficiency by even just 1% can ultimately save $25m a year.
But what can’t companies bank on? “Regulatory relief.” The two little words FDA began throwing around when talks of QbD and PAT became mainstream. Those two little words soon transformed into “regulatory flexibility.” And now even those are heading out the door. It seems, from what I’ve heard in tidbits here and there at Interphex, that FDA needs to treat companies implementing QbD on a case-by-case basis. There won’t be a formal agreement or guideline coming anytime soon (or probably ever) that outlines the regulatory “relief” or “flexibility” that companies can expect. While cleaner audit trails and processes may make inspections smoother or quicker, points out Stephens, companies looking to start up PAT in their manufacturing units should probably focus on how they can save money with PAT, not get out of FDA oversight.
Actually, one should measure and control CPPs in order to obtain good quality product. CQAs are a much broader concept that includes caracteristics of the final product as well as RM attributes or IPC’s, for example.
But I agree that PAT or even QbD shouldn’t be used as an excuse to expect less FDA oversight.
The FDA has a responsibility to protect the interests of the public. My 30 years of experience with numerous remediation consent decree, warning letter, 483’s projects indicates the end product of the FDA’s new product submission review and actual site inspection activities is VARIED quality due to the varied quality of its work force. The medical device industry seems to be ahead as compared to pharma in relation to regulatory compliance and overall productivity. The pharmaceutical, medical device and overall healthcare industries continue to look for creative ways to deliver bottom line results to their stockholders EVERY quarter by doing the ABSOLUTE minimum relative to FDA compliance. The success formula – solution to this challenge is simple yet VERY difficult to implement, especially for very large size companies: Understand your customer needs; design and prove feasibility of a product that could satisfy those needs; develop and validate a bench manufacturing process that could produce a product of consistent quality; transfer PROPERLY the already well-understood and documented technology, etc. to manufacturing; launch the product; continuously improve the product based on a ROBUST change control, CAPA, and overall Quality System, and the bottom line issue will take care of itself. Lots of companies don’t understand how their products are being manufactured; what are their CPPs, CQAs; have inept change controls, CAPAs and Quality Systems, and then they wonder why they got problems … Companies need to go past the various buss words of every year and instead focus on the CORE issues that guarantee to produce for their stockholders significant and quantifiable bottom line benefits now and in the future. This is not utopia; it can be done with the right strategy, correct identification of current root causes and then proper implementation of a fast and effective, regulatory compliant action plan.