The next component of the FDA and the European Medicines Agency cooperative clinical inspections program will be both narrower in scope and wider in reach, focusing on bioequivalence studies conducted at sites around the globe.

The two regulatory agencies announced Dec. 18 they will collaborate and share information on inspections of clinical and analytical facilities that conduct bioequivalence studies submitted to support generic small molecule drug applications.

Five EU member states – France, Germany, Italy, the Netherlands and the United Kingdom – as well as the EMA will participate in the program since generic marketing authorizations in Europe often are obtained by mutual recognition/decentralized/national procedures.

The EMA-EU MSs-FDA Initiative on Inspections for Generic Applications is an extension of an effort begun by the two agencies in 2009 to share information and best practices and cooperate on inspections of pharmaceutical clinical trial sites and studies to ensure compliance with good clinical practices. That effort focused on new drug applications for sites located in the U.S. and the European Union, whereas the new effort will be conducted at “sites all over the world.”

While expanding the global extent of the U.S./European GCP cooperation, the effort on generics will target facilities involved in bioequivalence studies, which typically are conducted at a single laboratory, compared to the multiple sites that participate in drug trials.

Prioritizing Workload

Leveraging the bioequivalence inspection resources of the European countries with those of FDA will not necessarily result in faster approval of ANDAs. “In the short term, we anticipate this program will not significantly affect the speed of FDA’s application approval rate,” the agency told “The Pink Sheet.”

What it will do, the agency said, is provide information on the quality of work conducted by bioanalytical firms not subject to a recent visit from FDA. It also will give the agency insight into how other inspectors do their jobs and “may help us to prioritize our inspections workload,” the agency noted.

The latter will be a criterion for the program’s success, according to FDA. “Early success means that information exchanged was useful toward inspections planning.”

The bioequivalence initiative follows up on a pledge by FDA in the generic drug user fee commitment letter negotiated with industry to look at how it could use information from inspections by foreign regulators to help bring parity to its inspection programs for domestic and foreign facilities. The letter specifically mentioned inspections for bioequivalence and good manufacturing practices.

The goal is to reduce the strain on FDA resources and minimize the impact on generic drug manufacturers from multiple inspections Also see "Generic User Fee Agreement Includes FDA Pledge To Determine Best Use Of Foreign Regulator Inspections" - Pink Sheet, 7 December, 2011..

Inadequate resources have led the agency to look abroad to other regulators to share the workload. An early EMA/FDA effort focused on GMP inspections to eliminate duplicative efforts Also see "EMA And FDA Co-Operate To Reduce GMP Inspections Burden" - Pink Sheet, 16 August, 2010..

A strain on resources prompted FDA to close its Amman, Jordan, office Also see "FDA To Close Office In Amman, Jordan; Operations Moving To White Oak" - Pink Sheet, 23 September, 2013..

In addition to turning to other agencies for support in inspections, FDA is developing an internal database that puts all facility data and compliance history in one location to facilitate oversight of those involved in both brand and generic drug manufacturing Also see "FDA GMP “Surveillance” Will Link Quality, Compliance Information To Inspections" - Pink Sheet, 25 November, 2013..

Similar To Initiative For Clinical Trial Inspections

The generics program will operate separately from the EMEA-FDA GCP initiative, but under the same terms of engagement when those align with the objectives of the bioequivalence initiative.

An assessment in 2011 of the first 18 months of the GCP inspection program for clinical trials showed progress toward improving communications between EMA and FDA about inspections. However, at that time, the agencies noted the need for additional inspections before they could accept each other’s findings Also see "Practice Makes Good: FDA, EMA Focus On CROs As GCP Info Sharing Improves" - Pink Sheet, 8 August, 2011..

The bioequivalence initiative has four objectives:

Periodic information sharing on inspections, including timely communication of negative outcomes that reveal systemic problems at a site that could call into question the reliability of data from all studies conducted at the site
Joint inspections, which occur when FDA and European inspectors are on site at the same time or in an overlapping time period and produce separate reports in compliance with their agency’s policies and procedures
Observed inspections, which involve an inspection by one agency’s personnel while observers from the non-inspecting authority are present to observe and learn about similarities and differences in process and procedures and gain an insight into how to interpret the inspecting agency’s findings
Training opportunities to improve bioequivalence inspections

The confidentiality arrangements between the European Commission, the EMA, interested EU member states and FDA will govern the bioequivalence initiative.

FDA/EMA Bioequivalence Collaboration Is Narrow In Scope, Wide In Reach

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