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FDA and Industry: Working together to mitigate GMP-related drug shortages

While drug shortages continue to make headlines, recent news has been highlighting how regulators and industry are working together to mitigate the impact of potential drug shortages instead of emphasizing the dire circumstances patients are facing as a result of these shortages. Most recently, FDA and Merck’s subsidiary, Organon Teknika, announced plans to increase production of the oncology drug, BCG, in response to a shortage resulting from the temporary shut-down of Sanofi Pasteur’s BCG plant following an FDA warning letter issued in June 2012. This announcement comes on the heels of Congress’s blistering criticism of FDA’s management of the drug shortage crisis, which suggested that FDA facility inspections were too aggressive. FDA defended itself in a letter to Congress on July 23, 2012 by saying that it was forced to act because some manufacturers were producing products that could be dangerous to patients. As emphasized in our recent blog, GMP- compliance failures have been on the rise at many manufacturing facilities, and while FDA actions are not the sole cause of drug shortages, more than half of all drug shortages were associated with manufacturing problems, including quality-related issues.

One of the largest patient populations affected by drug shortages has been those receiving generic injectable oncology drugs, which make up over 16% of the current drug shortages. Johnson & Johnson’s cancer drug, Doxil, has been in short supply since its supplier, Ben Venue Laboratories, closed its manufacturing facility last year due to extensive compliance issues (see our earlier blog on this topic). In addition to the impact this shortage had on patients, this shut-down had significant negative consequences for pharmaceutical developers since Doxil was being used in 30 different clinical trials as part of a combination treatment or as a comparator drug for a control group. The shortage of Doxil, and other generic injectable oncology drugs, has forced many companies to delay or slow down their clinical trials at enormous cost to both the companies and patients.

In another example of industry-regulator collaboration, FDA has allowed “temporary, limited importation” of Lipodox, a foreign version of Doxil manufactured by Sun Pharmaceuticals, until the shortage of Doxil in the United States is resolved. With Lipodox now available in the US, Johnson & Johnson said it would be able to release some Doxil for use in clinical trials, much to the relief of many product development companies who can now resume their clinical trials.

While some resolutions, like the Lipodox outcome, have been implemented to address critical drug shortages, it is clear that greater visibility into supply status is needed to prevent or mitigate the impact of future potential drug shortages. The Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law in July, 2012, provides this visibility by expanding drug shortage reporting requirements, and requiring that FDA consider the impact of warning letters or other enforcement actions on drug supply. FDA will continue to be in the precarious position of “Damned if they do, damned if they don’t” whenever they take action against certain manufacturers for compliance issues, but it is incumbent on industry to make the necessary investments and be vigilant about cGMP compliance so FDA is not compelled to take action. While the causes of drug shortages are multi-dimensional and cannot be solved overnight, it is encouraging to see such proactive collaboration between industry and regulators in response to the drug shortage crisis.



Blog article by: Patti Seymour