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Likewise, when your CMO is suddenly overwhelmed by a severe FDA warning letter, and it decides the problems are too expensive to fix and closes the only plant making your product, which one of you caused the situation? In a strict regulatory sense, you did. "The drug sponsor will always be and should be held more responsible than the CMO. Ultimately, the sponsor is the one responsible for patients' safety — and the one who will get sued if adverse events lead to lawsuits," says Dr. Brian James, Ph.D., VP of operations, Rondaxe.
We spoke with James because of his experience with both sides of the pharma-company/CMO relationship, formerly managing outsourcing of key intermediates at Bristol-Myers Squibb and now overseeing independent manufacturing audits for pharma and CMO clients. His insights form the backbone of this article as a guide to dealing with potential disruptions — and sometimes significant interruption — in product supply when your CMO develops problems noted by FDA inspectors in Form 483s and warning letters.
Examining the various situations and worst-case scenarios companies may face — such as Ben Venue's shutdown of Doxil production for Janssen — James outlines ways to determine
the best course of action when the CMO faces regulatory problems. He suggests how you can define and mitigate the risks and evaluate the potential costs associated with switch- ing suppliers. But his most important advice may be directed at pharma-company CEOs and other top management, who, he says, must learn to recognize manufacturing quality as a strategic issue of risk management, warranting their personal involvement and support.
WEIGHING PREVENTION
Most production errors found in FDA inspections are minor, James says, so they can quickly be addressed and fixed, often before the inspector leaves the plant. Bigger problems emerge or become more obvious when errors pile up beyond the two or three items typically noted in 483s. But the origins of large faults in a production line can lie in small or even overlooked errors.
"In audits, when the CMO managers tell me proudly that their last inspection produced no 483s, I say the inspector must have missed something," recalls James. "Usually I find several minor items that were overlooked. A good auditor stays a step ahead
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The CMO Leadership Awards 2012