A Nuclear Approach to Preventing Drug Shortages

Amgen embraces the U.S. Navy’s safety philosophy to fight shortage-causing quality excursions

By Steven E. Kuehn

For those not familiar, even at the dawn of the nuclear power era, it was well understood that in all operations having to do with generating power via nuclear fission, safety was paramount. After all, it was Fermi’s intention to safely control the reaction to benefit mankind. As early as 1946, the U.S. began exploring ways to harness the energy and apply it to naval propulsion, an effort led by Hyman G. Rickover, an enigmatic character who essentially created the U.S. Nuclear Navy. Rickover is widely credited with fostering a safety culture in the Navy that continues to maintain a record of zero reactor accidents. Known as “Defense-in-Depth,” to the Navy and the commercial nuclear power industry, the philosophy has served the Navy well for decades and is now being called on to do the same for one of the most prominent biopharmaceutical companies in the U.S., in its efforts to halt drug-shortage causing quality excursions. According to Madhu Balachandran, Amgen’s Sr. VP, preventing critical drug shortages is one of the Pharma industry’s strongest imperatives.

That admonition was delivered at the beginning of Balachandran’s keynote remarks to attendees of the recent PDA/FDA Joint Regulatory Conference held in Washington, D.C., in early September. In his talk, titled “Perspectives on Biotech Manufacturing of the Future,” Balachandran posited that next-generation manufacturing technology will play a key role in minimizing the likelihood of drug shortages and how at Amgen, its defense-in-depth-guided risk management strategy is literally defending its processes from being “attacked” by contaminants and other threats to drug manufacturing quality.

Balachandran noted that the industry’s record of shortages remains a sad story saying that, since 2011, there’s been a four-fold increase. Asking attendees “What are the principal reasons of these drug shortages?” Citing product quality issues, insufficient capacity and raw materials, Balachandran offered his personal experience dealing with a glass delamination issue that caused Amgen to recall one of its most prominent biotherapies. “We knew that a primary component [glass vials] was in short supply and there were attempts to increase throughput and [have] the manufacturer increase line speed.” Balachandran explained that the temperature control in forming the glass was not adequate and the quality system apparently not strong enough to detect excursions and variations. When the surface of the glass had been exposed to the protein and pH of compound long enough, the now familiar phenomena of glass delamination had struck, prompting an expensive recall for Amgen (as well as other companies coping with the same issue) and ultimately shortages.

To make gains against quality issues and shortages, Amgen instituted a set of initiatives including prevention, technology, inventory and diversification. Balachandran noted that his colleague Martin Van Triest once told him “there are three things important to prevention: The first is the quality system; the other two are not important!” This elicited a knowing chuckle among attendees, who understand that if the quality system is not strong, “the rest of it — technology, inventory, diversification — none of that really matters, does it?” He also talked about Amgen’s investment in a thermal technology that zaps viruses in the medium rather than expensive, damaging CIP regimes. Tighter inventory controls for better supply chain transparency and diversifying production assets geographically to assure supply continuity sum up how Amgen applies its anti-shortage initiative efforts.

Balachandran spent the rest of his talk describing the rigor of a defense-in-depth-based quality and risk management regime and how it is being applied at Amgen. Describing how the Navy’s defense-in-depth principles take a systematic approach to delivering highly reliable operations even in complex and risk-laden environments, Balachandran noted how it manages the three primary pillars of its effort: People, Process and Equipment. “Now that seems obvious to most of you in the room; how can you run an operation without them,” he said. “But it’s the way the Navy does it that sets it apart; they’re obsessive and uncompromising in their attention to detail.”

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