FDA's drug shortage prevention guidance draws fire from PhRMA, BIO and Bristol Myers

Several months after the FDA unveiled a framework to help manufacturers forge risk management plans aimed at combating drug shortages, two trade group heavyweights are sounding their discontent.

Late last week, the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO) lobbed comments at the FDA’s draft guidance, issuing similar rebukes as those made by outfits like Civica and the Biosimilars Forum.

While PhRMA said it “appreciates” the FDA’s differentiated approach to supply chain risks for varied drug products, plus the risk factors the agency has outlined,” the trade group “believes the draft guidance would benefit from a number of changes to enhance clarity for stakeholders developing and implementing [risk management plans] to mitigate drug shortages.”

BIO, meanwhile, took umbrage with certain terminology used in the FDA’s guidance alongside timing and structures for communication.

While the FDA claims it has eased or prevented “hundreds of new drug shortages” in the U.S. over the past decade, quality problems, global supply chain weaknesses, unexpected demand spikes, market withdrawals and natural disasters continue to threaten the nation’s stock of pharmaceuticals, the regulator warned in May.

To mitigate the problem, the regulator issued draft guidance that would require producers of certain drugs and drug ingredients to roll out risk management plans. For others, the move is simply recommended.

The FDA’s plan specifically mandates risk management plans for medicines used to treat rare diseases, drugs that lack “appropriate alternatives” and medical countermeasures against public health emergencies.

As for the rebukes coming from the two trade groups, PhRMA began its critique with recommendations on how the FDA could fine-tune its terminology. Specifically, PhRMA wants FDA to adopt phrasing that harmonizes with recent international manufacturing guidelines. For instance, the trade group suggests FDA use the term "hazard identification" rather than "risk identification."

“Rather than using different terms and concepts that could create confusion or introduce inconsistency, PhRMA recommends that, in finalizing this guidance, FDA align with the terminology and concepts” presented in certain other manufacturing guidelines, PhRMA explained.

BIO, for its part, specifically took issue with phrases like “primary,” “secondary” and “other stakeholder” to describe manufacturers, which the trade group branded “very broad.” The wide terminology could be interpreted to mean manufacturers at any step of the manufacturing process—including drug ingredient or drug product manufacturing—would need to prepare risk management plans (RMPs). That requirement would be “highly burdensome” to active pharmaceutical ingredient makers as well as companies engaged in the intermediates business.

BIO also recommends FDA use the term “drug substance” in lieu of API, which specifically refers to small-molecule drugs. The trade group wants further clarity for drug ingredient makers in general, and, to that end, it’s pressing the FDA to publish a list of APIs that would be subject to the new rules.

Besides terminology problems, PhRMA and BIO both flagged timeline issues. PhRMA is pressing the FDA to use a risk-based approach to revise RMPs, rather than each year as the draft guidance currently suggests.

As for the timing of RMP reviews, PhRMA figures frequent checks and revisions could be necessary early in a product’s life cycle or when a manufacturer has switched to a new supplier.

“On the other hand, RMPs for products with long-established supply chains may not need annual review and revision,” PhRMA said.

BIO also took issue with the guidance’s timing, though its complaint hinges on the FDA’s failure to lay out a clear timeline to employ the final framework. The trade group further argues that manufacturers have had little time to prepare for the change, and it has asked for a period of “at least” two years from publication of the final guidance before RMPs become part of FDA’s record requests during inspections.

PhRMA wants the FDA’s guidance to pay heed to existing “Pharmaceutical Quality System” processes “used to maintain a state of control and drive continuous improvement.” These could in turn be leveraged to support RMPs as well as the review process, where appropriate, PhRMA argued.

PhRMA also suggests that manufacturers with “similarly situated products” don’t need to reinvent the wheel when it comes to their RMPs.

“For example, RMPs for products that source the same raw material from the same facility can utilize the same risk mitigation approach to geographic risk factors,” PhRMA explained. “This approach would help appropriately manage resources and maintain consistent approaches.”

Overall, PhRMA believes the FDA’s draft guidance “largely complements ongoing industry efforts,” though there’s room for the framework to be “enhanced.”

Finally, communication is key, BIO stressed. Whereas the FDA’s guidance recommends “primary stakeholders” share their risk management plans with “secondary” and “other stakeholders” such as contract manufacturers, BIO believes “two-way sharing of information should occur from contract manufacturing organizations.”

“The primary stakeholder is ultimately responsible for the availability of the drug and furthermore has leverage over their contractors through their contracts and quality agreements,” BIO explained.

As for other groups, government-funded nonprofit Civica, Mayo Clinic and Sanford Health have all generally supported the FDA’s move, though they say there’s a chance to thwart or mitigate shortages by improving upon inventory management once a supply squeeze has been identified, Endpoints News previously reported.

Others, such as the Biosimilars Forum, blasted the draft guidance and warned it could sow confusion.

“The Draft Guidance is not consistent with the law and will impose a heavy burden on industry that will undermine the desired objective of mitigating shortages and may actually exacerbate them,” the forum said in comments submitted to the FDA early last month.

Trade groups aren’t the only ones making their voices heard. Industry juggernauts like Bristol Myers Squibb have also weighed in.

BMS, like many others, said it appreciated the FDA’s overall efforts, adding the caveat that several aspects of the guidance “are not clear with respect to execution, FDA expectations and overall processes used to mitigate drug shortages and would appreciate some clarification/guidance.”