In 1998, the EU and the US signed a broad Mutual Recognition Agreement (MRA), which included a Pharmaceutical Annex providing for anticipated and limited reliance on each other’s Good Manufacturing Practice (GMP) inspections. However, this Agreement was never fully implemented.
Since May 2014, teams from the European Commission, the European Union (EU) national competent authorities, European Medicines Agency (EMA), and the United States Food & Drug Administration (US FDA) have been auditing and assessing the respective supervisory systems.
In June 2017, the European Commission confirmed that the US FDA has the capability, capacity, and procedures in place to carry out GMP inspections for human medicines at a level equivalent to the EU.
November 1, 2017, marked the entry into operation of the agreement between the EU and the US to recognize inspections of manufacturing sites for human medicines conducted in their respective territories.
In July of 2019, the FDA completed its assessment of all 28 EU GMP inspectorates for human medicines. This assessment confirmed that they have the capability, capacity, and procedures in place to carry out GMP inspections at a level equivalent to the US.
July 11, 2019 Milestone
The FDA confirmation completed the transitional phase of the MRA process, making the MRA fully operational on July 11, 2019.
“We welcome the implementation of this agreement, which means authorities on both sides of the Atlantic will now be able to rely on each other’s inspection results. This milestone is a testimony to the importance of our strategic partnership with the US. It will support making best use of our inspection capacity so that patients can rely on the quality, safety, and efficacy of all medicines, no matter where they have been manufactured,” said Guido Rasi, Executive Director of EMA.
The FDA will continue to perform some inspections in EU countries with capable inspectorates, such as product manufacturing assessment inspections to support marketing approval decisions. However, the FDA expects to perform fewer routine surveillance inspections in EU countries with a capable inspectorate.
The MRA covers Routine Surveillance Inspections for the following:
- Marketed finished pharmaceuticals for human use in various pharmaceutical dosage forms such as tablets, capsules, ointments, and injectables, including:
- Marketed biological products:
• Allergenic products
- Active pharmaceutical ingredients or bulk drug substance
The MRA does not currently apply to the following products:
- Human blood and plasma
- Human tissues and organs
- Veterinary immunologicals
- Advance therapeutic medicinal products
What does this mean in practice?
The EU and the FDA will not duplicate routine surveillance inspections within each other’s territories. However, the MRA does allow for the right to inspect in each other’s territory at any time.
The EU and the FDA have the option to rely on inspection reports issued by a recognized authority for manufacturing facilities located outside their respective territories. However, this provision in the MRA to accept the outcome of inspections conducted outside the US or the EU is not yet operational, and further guidance will be published in due course.
As of July 11th, importation testing in the EU for human medicines as laid out in Article 51 paragraph 1 of Directive 2001/83/EC will not be required provided that the product was manufactured and tested in the US. Each batch/lot should be accompanied by a batch certificate issued by the manufacturer, certifying that the product complies with marketing authorization requirements and should be signed by the person responsible for releasing the batch/lot.
Expansion of Operational Scope to include:
- Veterinary medicines: by December 2019
- Vaccines for human use and plasma-derived medicines: by July 15, 2022
- Guidance for reliance on GMP inspections outside of EU & US to be published
About the Author:
John has more than 23 years of experience providing technical and consulting services in cGMP pharmaceutical and biotechnical environments. John is an experienced QP with several years’ experience releasing both commercial and clinical material to market. John is a Quality Systems SME. He understands FDA and EU regulations, regulatory guidance documents, and ICH guidelines and has applied the knowledge to develop risk based approaches for several applications. John has significant experience in GMP/ISO compliance auditing of manufacturing facilities and supply chain.