EU and FDA Reliance Regarding Drug Manufacturer Inspections

On December 7, 2016, Dara Corrigan, J.D., the FDA’s Associate Commissioner for Global Regulatory Policy, introduced the Mutual Reliance Initiative (MRI).


For FDA professionals focused on drug quality and safety, the rapid increase in imported drugs from nations where the FDA devotes limited inspection resources is of great concern. One way to address this concern would be to create an expanded inspectorate, one in which investigators and inspectors from the FDA and trusted partners, such as those in the European Union, would work together, rely on each other’s inspections, avoid duplicating inspections, and conduct more inspections in areas where the increase in drug manufacturing has greatly increased, such as China and India.


To meet this challenge, the FDA responded with the Mutual Reliance Initiative (MRI). The concept is simple. EU country inspectors would continue to inspect in their respective countries, the FDA would continue to inspect the manufacturing facilities in the U.S., and the EU and FDA would rely upon each other for inspections in other parts of the world. The MRI is designed to prevent duplication, lower costs, and enable the regulators to devote more resources to parts of the world that present greater risks. The savings would be considerable – over the past five years, approximately 40 percent of the FDA’s drug inspections were performed in the EU.


There is a history of U.S.-EU collaboration. In 1998, in an annex to a U.S.-EU trade agreement, the U.S. and the EU agreed to recognize each other’s good manufacturing practice drug inspections. However, the agreement was never fully implemented.


Since 1998, the FDA expanded its reach beyond U.S. borders by opening foreign offices in China, Europe, India, and Latin America. The FDA now conducts more foreign inspections and has gained more than 15 years of experience collaborating with the EU.


Equally important was the 2012 passage of the Food and Drug Administration Safety and Innovation Act. Recognizing that the FDA cannot and should not monitor the world’s drug inventory by itself, Congress authorized the FDA to accept the findings of a foreign inspector when the other country’s drug inspectorate is capable of conducting inspections that meet U.S. standards.


The MRI was launched in May 2014. As part of MRI, the FDA and the EU assembled dedicated teams to assess the risk and benefits of entering into a mutual recognition agreement. The FDA was invited to observe the EU’s Joint Audit Programme, in which two EU nations audit the inspectorate – the regulatory authority – of another member. The FDA first observed the audit of Sweden’s inspectorate by auditors from the United Kingdom and Norway. Since then, the FDA has observed an additional 12 audits of drug inspectorates across the EU with more audit observations planned through 2017.


This unprecedented access allows FDA observers to gather firsthand knowledge of the laws that govern EU good manufacturing processes drug inspections and how inspectorates manage the drug inventory within their respective borders. Also, interacting with auditors across the EU provides a unique opportunity to understand the regulatory framework in the EU. With 28 member states (27 after Britain leaves the EU), there can be differences the FDA must understand.


Corrigan clarified that the so-called “Brexit” had no impact on the FDA’s relationship with its United Kingdom counterparts. Once the UK finalizes its departure from the EU, the FDA and the UK will reexamine existing commitments and, if necessary, renegotiate any existing agreements. According to reports, it is likely going to take the UK and EU two years to finalize the terms of the Brexit.


MRI is one of the key components of the pharmaceutical sector covered in the Transatlantic Trade and Investment Partnerships (T-TIP), but could also take another path if the initiative progresses more quickly than the trade negotiations.


The observation and analysis of the drug inspectorates in the EU has only been possible because of the extraordinary devotion and collaboration across the FDA. Observers of the audits have included subject matter experts, management, and investigators from the Center for Biologics Evaluation and Research, the Center for Drug Evaluation and Research, the Office of Regulatory Affairs, and the Office of Global Regulatory Operations and Policy. These and other FDA employees guided the FDA successfully through the EU’s audit of the FDA in September 2015, when the EU visited three district offices, the main FDA campus, and a drug laboratory as part of its assessment. The EU team applied the same criteria that it applies within the EU when it audits its own member states.


Looking forward, the FDA hopes to sign an agreement with the EU soon and is working to complete assessments of the capability of the drug manufacturing inspectorates of two to four other countries within the EU.


These first steps with the EU will lead toward the agency’s goal of an expanded inspectorate, containing investigators and inspectors from the FDA and across the EU. These collaborations will enhance the FDA’s ability to evaluate risk, produce better data, and minimize public health risk globally. Indeed, the need to engage globally in different ways is imperative.


See the FDA Voice Blog Post


See also Medical Law Perspectives, May 2013 Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication