FDA Moves Forward on Mutual GMP Inspections with Europe

The need to inspect a growing volume of overseas pharmaceutical manufacturers, but limited FDA resources for foreign operations, is prompting completion of a Mutual Recognition Agreement (MRA) that will permit US and European Union regulatory authorities to rely more on each other’s inspection reports. By reducing the need to inspect all of the more than 1000 registered drug production facilities in Europe, FDA would avoid duplicate site visits and free up resources to support greater oversight of the burgeoning number of drug production facilities in China, India, and other nations that ship medicines to the United States.

After several years of negotiation and collaboration, US and EU officials signed an agreement in March 2017 to extend and conclude the MRA negotiating process, which began in 2014, explained Dara Corrigan, FDA associate commissioner for global regulatory policy. The aim is to finalize the agreement in July 2019, she said at the annual meeting of the Food and Drug Law Institute (FDLI) in May 2017. When in effect, the program will provide FDA and the European Medicines Agency (EMA) with redacted inspection reports. These will identify facilities with strong records of compliance with good manufacturing practices (GMPs) and support decisions on whether there is a need to re-inspect a facility. In 2016, FDA inspected approximately 400 drug operations in the EU, and only 5% led to an Official Action Indicated (OAI) classification. At the same time, such compliance findings are more frequent following FDA inspections of drug manufacturers in China, illustrating the need for the US to visit more facilities in Asia and other regions. 

The main thrust of the MRA negotiations over the past three years is to devise a system that supports mutual reliance on inspection reports by other competent regulators. The EU has a Joint Audit Programme to assess the oversight capabilities in the 28 EU member states, each of which conducts its own inspections of pharmaceutical facilities following different practices based on differing standards. So far, FDA has observed eight joint inspection audits, ranging from Greece and Croatia to Germany and the United Kingdom, where investigators from two other EU member states assess a third operation.

At the same time, EU officials are auditing FDA’s inspection program and observing US site visits to lead to EMA decisions to forego a redundant inspection of a US facility. The current schedule calls for the EU to complete its assessment of FDA inspection operations by July 2017 and for FDA to formally recognize inspection operations in eight EU member states by November 2017. The aim is for FDA to complete all EU member state assessment by July 2019.

The current MRA program covers most drugs and biotech therapies. Corrigan noted that extension to vaccines and veterinary products will be evaluated in the future. The final agreement also aims to end the need for batch inspections of US-made products shipped to Europe.

While the current initiative applies to GMP compliance inspections, there may be certain conditions when pre-approval inspections (PAIs) might be covered. FDA and EU officials are examining how PAIs differ and are the same in the two regions, and FDA’s frequent need to complete such inspections in very limited timeframes. An agreement may permit FDA or the EMA to request that a capable authority conduct a PAI by a certain date, but such a program will require further deliberations.