Mind the Gap: Strengthening relations with the European Medicines Agency to the benefit of public health

David Martin, M.D., M.P.H.

Cars driving on the left side of the road and exhortations to “mind the gap” when exiting the underground became a part of my daily routine when I joined the FDA Office of International Programs as the Acting FDA Liaison to the European Medicines Agency (EMA) in London. EMA is an important partner for the FDA: It coordinates a network of 4,500 European scientists and evaluates and supervises human and animal medicines for more than 500 million people in 31 countries.

Sabine Haubenreisser and David Martin

EMA’s Sabine Haubenreisser, MSc, Ph.D., and David Martin, M.D., M.P.H., who served as the Acting FDA Liaison to the European Medicines Agency from June through September 2014.

On my first day at the EMA, I learned that its Pharmacovigilance Risk Assessment Committee (PRAC) was debating a suspension of the European marketing authorization for a product approved in the United States by FDA. Moreover, PRAC was seeking urgent action within a week, which required quick response by FDA. Without it, suspension of a marketing authorization by Europe for an FDA-approved product could be confusing to patients, medical care providers, and industry in the U.S.

Consulting with management, review team members, and the international team from the FDA Center for Drug Evaluation and Research (CDER), I described the decision points to be addressed by the Europeans. The CDER team was already conducting a preliminary epidemiologic analysis of the possible relationship between the product and the adverse event in a large U.S. medical claims database. EMA had been already made aware of the ongoing CDER analysis, but needed formal detailed information to include in its benefit/risk assessment. PRAC had to be briefed on the broad outlines of the FDA evaluation within 48 hours, and needed access to FDA’s interim analysis within two weeks.

After a quickly arranged briefing under the auspices of an FDA-EMA confidentiality arrangement, CDER completed and shared the analysis in less than one week. At a follow-up meeting, FDA, EMA, and PRAC experts reviewed all data sources. The information indicated that the benefits of the product outweighed the low potential risk of adverse events. This information was included in the formal review by the PRAC, and a majority of PRAC members voted to maintain the product’s marketing authorization.

This episode showed  the importance of reciprocal FDA and EMA representation at each agency, which is currently carried out by EMA’s Sabine Haubenreisser, MSc, Ph.D. in FDA’s headquarters in White Oak and FDA’s Amy Egan, M.D. in London. Contacts between the liaisons and host agency leadership facilitate strategic dialogue that informs future policy making. And through close observation of the U.S. and European regulatory agencies in action, the FDA and EMA liaisons can help both sides find common ground when they are faced with regulatory decisions that could impact global public health.

David Martin, M.D., M.P.H., served as the Acting FDA Liaison to the European Medicines Agency from June through September 2014. He is the Director of the Division of Epidemiology within FDA’s Center for Biologics Evaluation and Research.

About EMA: European Medicines Agency

EU facts and figures: European Union

EMA/FDA confidentiality agreement: International Programs

FDA and Sub-Saharan Partners Protecting Public Health

By: Beverly Corey, DVM

FDA and its partners in Sub-Saharan Africa have made great strides in improving the oversight of the clinical trials of medical products in development—an important advance in protecting public health in both the U.S. and Africa.

This is important not only to protect the Africans who are participating in these tests of medical products, but also because the FDA and other regulatory authorities must rely on the results of these studies when reviewing marketing applications for the products.

FDA’s Office of International Programs (OIP) established its Sub-Saharan Africa Post in Pretoria, South Africa, in June 2011. We have been building regional relationships that allow us to share information about FDA policies and procedures, and to better understand the regulatory landscape there. The latter is no small feat in this vast region of 54 countries with varying degrees of regulatory strengths and capabilities.

However, our collaboration with the Southern Africa Development Community (SADC), which represents 15 African nations, has allowed FDA to strategically engage in strengthening regulatory capacity in the area of Good Clinical Practices (GCPs) and clinical trial inspections. These practices, and the inspections to ensure that they are followed, are designed to protect the integrity of data produced by the trial and the safety of its participants.

This activity has given expertise to regulators who did not think their knowledge base was extensive enough to audit (monitor) and inspect clinical trials. Regulators in countries that once did not audit clinical trials are now doing so. With more than 2,000 clinical trials being conducted in Africa—over half of them in South Africa—this is a momentous public health achievement. 

GCP team members meet with the principal investigator and staff at a TB clinical trial site

The Sub-Saharan Africa Post conducted a successful FDA/SADC Good Clinical Practice Inspection training from August 24-28, 2012, in Lusaka, Zambia. Thirty six drug regulators from 13 SADC countries participated, including Angola, Botswana, Lesotho, Malawi, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Swaziland, Tanzania, Zambia and Zimbabwe.

This was the third in an FDA training series—typically offered in three to four phases—to develop trainers who have expertise in clinical practices and inspection. These individuals will also be prepared to train others within their agencies and the regulated community.  

This particular workshop was designed to reinforce lessons learned and provide additional inspectional experience for those who completed workshops in the first two training phases in Botswana in 2010 and in Pretoria in 2011. The goals of Phase 3 include reviewing core knowledge and skills, preparing inspection reports and inspectional observations; acquiring additional mock inspection experience at clinical investigator sites; gaining experience with new types of study protocols; and promoting regional networking.

These countries continue to make substantial progress in the oversight of clinical trials. For example, at the onset of our first training, only three of 13 participating countries were involved in how clinical trials are conducted. We now have an additional two countries conducting oversight, with others poised to start soon. Other milestones from our training include important advances towards systematic oversight in Botswana, Mauritius, Swaziland, Tanzania, Zambia and Zimbabwe.

The definitive winner here is public health, both the health of the African people who participate in the trials and the health of the patients who may one day be taking these drugs being studied.

Beverly Corey, DVM, is the Senior Regional Advisor for  Sub-Saharan Africa, FDA Office of International  Programs, US Embassy, Pretoria, South Africa