Measuring the Impact of the Pharmaceutical Annex to the U.S./EU Mutual Recognition Agreement

December 6, 2019

By Mark Abdoo

When we first began discussing the prospects of a mutual recognition agreement with the European Union, in which EU member state (EUMS) regulators and the FDA would agree to rely on each other’s factual findings from their good manufacturing practice (GMP) inspections of drug facilities, the potential benefits seemed obvious.

By relying on each other’s expertise and ability to conduct GMP inspections under the Pharmaceutical Annex to the U.S./EU Mutual Recognition Agreement, we expected to avoid duplicate inspections of the same facilities, especially for facilities with a strong record of compliance. And these efficiencies would allow us to reallocate our inspectional resources to areas of higher risk. Of course, we knew we would have to wait until the agreement was implemented before we could confirm these assumptions.

Developing the MRA took time and resources. Beginning in 2014, FDA experts were sent to Europe to observe EU officials audit each of the 28 EUMS inspectorates to assure that they could conduct inspections at a standard similar to a U.S. inspection. In addition, we had to establish confidentiality commitments with each regulator to allow for the sharing of non-public information contained in inspection reports and be assured that each EUMS had a framework for preventing conflicts of interest that provided a similar level of protection as those in place at FDA. The FDA completed this work for the most common type of drug manufacturing inspections in July 2019.

The FDA and the EU have been collecting data on the operational impact of the MRA ever since the first countries were found capable on November 1, 2017, and the numbers are quite promising. So far, the EU has conducted 29 inspections at FDA’s request and the FDA has conducted 14 inspections at the EU’s request. Moreover, FDA has deferred 157 inspections in the EU after review of the inspectional information provided by our trusted partners. We anticipate seeing an even greater impact now that the MRA has been implemented in all 28 EU countries for human drug products.

The need for such metrics was one of the recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM) in a recent report. FDA had asked an Ad Hoc NASEM committee to examine mutual recognition and mutual reliance agreements around the world (some dating back many years) and the committee found a surprising lack of data on the successes and challenges of these programs. To address that information gap, the committee called on regulatory authorities to create a results framework with clear indicators, metrics, and processes for monitoring and evaluating these programs. Such information would increase understanding of the program's public health benefits and enable benefit-risk analyses over time, the report's authors said.

We certainly agree that more data is needed on the U.S./EU MRA, beyond the operational data we’re collecting now. In fact, we're working with our EU partners to explore what additional metrics might be informative. Having sufficient data will help the FDA decide not only how to allocate our inspectional resources, but also the scope and breadth of future mutual recognition and mutual reliance agreements that might include other categories of inspections and product types, such as veterinary medicines. Since these other categories often involve different inspectorates in Europe than those audited for human pharmaceuticals, implementation could take some time. Yet, eventually, with metrics in place, we could confirm their benefits as well, allowing manufacturers to avoid unneeded inspections while ensuring that medicines are safer for patients.

Mark Abdoo is FDA's Associate Commissioner for Global Policy and Strategy