Fear. Anxiety. Sleepless nights. Terror of noncompliance. Remember those thoughts that raced through your mind when you heard a regulatory agency was going to inspect your facility? And then, multiply that by ten when you learned that not only members from the United States Food and Drug Administration (US FDA) were coming to inspect your facility, but that inspectors from one of the European Medicines Agency (EMA) Member States would arrive for an inspection just one week after the FDA completed their inspection. Take a deep breath, life is getting better! Finally, the execution of a historic agreement between the FDA and EMA means that those days are now behind you.

EMA and FDA have been in negotiations to complete and approve a Mutual Recognition Agreement (MRA) since 1998. The final MRA that was agreed to in November 2017 relied on robust data from inspections conducted by participating countries within the European Union (EU), who are members of the EMA, and the FDA. The data demonstrated that the inspection processes between the agencies were comparable when performing good manufacturing practices (GMP) inspections for human pharmaceuticals. The final MRA became fully applicable for GMP inspections and batch certification between 29 countries in the EU and US on July 12, 2019. The Mutual Recognition Agreement allows EMA and FDA to optimize their inspection capacity and eliminate the need for inspections from multiple agencies. This will enable patients to trust the safety, identity, strength, purity, and quality of all medicines, no matter where the products are manufactured or which agency inspected the manufacturer.

The participating EU countries and the US now completely recognize each other’s inspections of manufacturing sites for human medicines conducted in their respective territories by their respective agencies. However, the MRA included language that both EMA and FDA reserve the right to inspect in each other’s territory at any time. This situation could arise in connection with the submission of a supplement/variation that requires an on-site verification of GMP compliance if there is no recent pertinent inspection report available.

Implications of the Mutual Recognition Agreement

As described in Article 9 of the GMP Sectoral Annex of the MRA, the EU Qualified Person (QP) is relieved of the requirements of Article 51 of EU Directive 2001/83/EC (i.e., each production batch has undergone a full qualitative analysis within a Member State, a quantitative analysis of at least all the active substances, and all the other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorization). Additionally, the MRA authorizes importation of commercial drug product into the EU from the US without requiring batch testing in an EU member state, provided the tests were performed in the United States. Upon importation, documentation must be provided confirming the batch was manufactured in the US and must include a Certificate of Analysis issued by the manufacturer, signed by the person responsible for releasing the batch, certifying that the batch complies with requirements of the marketing authorization.

So, while the arrival of an inspector is still nerve-wracking, you can rest assured that there will most likely be only one Agency appearing at your doorstep for a GMP inspection. Furthermore, the MRA allows easier importation into the EU for both commercial and investigational medicinal products from the US, eliminating the requirement for review of the drug product manufacturing information including the batch record, testing, and GMP compliance review by a QP. Access to people in European member states for clinical trials is now more streamlined than ever before. If you plan to take advantage of the MRA and conduct clinical studies throughout the European Union, the expert advisors at Pearl Pathways can support your company’s Investigational Medicinal Product Dossier submission to EMA member states. Contact us today for a free consultation.

Authors: Mark Slisz and Beckinam Nowatzke