Since July 15th, 2019, the Mutual Recognition Agreement (MRA) is in effect. Following the completion of the FDA’s assessment of all EU Inspectorates, on July 11th.
In general, MRAs are agreements that promote market access and encourage greater international harmonisation of compliance standards. Both parties benefit from the agreement: it reduces the amount of duplicate inspections, which in turn allows them to allocate their resources to sites that pose a higher risk and at the same time it could help broaden the overall inspection coverage of the global supply chain.
The Mutual Recognition Agreement allows the FDA and EU health authorities to:
1. Rely on each other's GMP inspection system
The agreement is based on concrete evidence on both sides that their respective procedural frameworks for regulatory inspections of manufacturers are comparable and carried out equivalently. From the European perspective, teams consisting of professionals from the European Commission (EC), EU national competent authorities, and the EMA have visited several sites and HQ of the FDA. And the FDA has performed a full-fledged assessment of the respective supervisory systems of all EU Member states since May 2014.
2. Share their information on inspections and quality defects
The 2017 amended Sectoral Annex to the MRA that was implemented back in 1998 allows the FDA and the EU to use each other’s inspection reports and other related information obtained from these inspections to help determine whether a facility is manufacturing high quality drugs according to GMP guidelines. Based on the information from an inspection, both the FDA and/or EU can choose to conduct further inspections the ensure patient safety.
The FDA has stated that it will even begin using reports of inspections conducted earlier than the formal recognition date. To this purpose, the inspectorate determines an MRA Reference Date for each of the EU Health Authorities applying the following considerations:
Completion of a European Union’s (EU) Joint Audit Programme audit, with all corrective actions appropriately addressed
FDA’s review and determination that the EU’s conflict of interest provisions provide the same level of impartiality as the FDA
Completion of any corrective actions identified by FDA. This reference date will in fact precede the formal recognition date, which generally coincides with an MRA milestone deadline.
3. Waive batch testing of products on import into their territories
The MRA already facilitated cost reduction in the pharmaceutical industry by reducing the number of inspections taking place at facilities. It now also reduces costs for manufacturers by waiving re-testing of their products upon importation.
“The MRA states that from 11 July 2019, qualified persons (QP) in the EU Member States will be relieved of their responsibility for carrying out the controls on human medicines laid down in Article 51 paragraph 1 of Directive 2001/83/EC."
There are certain conditions that apply to this statement, of course:
verification that the product was manufactured in the United States
the controls have been carried out in the United States
each batch/lot is accompanied by a batch certificate issued by the manufacturer
The mutual recognition agreement between EU and US regulators strengthens reliance on each other's inspection expertise and resources. Mutual benefits for EU authorities and the FDA mentioned by EMA include:
the ability to focus inspection resources on other parts of the world where active pharmaceutical ingredients and medicines for the EU or US markets are manufactured
prioritising inspections of medicines manufacturing sites for higher risk cases;
reassuring patients that they can rely on the quality, safety and efficacy of all medicines, no matter where they are manufactured
improving the ability to identify and address potential problems at manufacturing sites before they become a public health risk
reducing the administrative burden and costs from duplicative inspections for pharmaceutical manufacturers, including smaller producers
History of MRA events so far
Although it is a huge milestone for the international pharmaceutical industry that the MRA is now operational, there are still some steps to be taken. A wide variety of the pharmaceutical products are included in the amended MRA, but medicines derived from blood or blood plasma, vaccines, or veterinary drugs are not yet covered. Medicinal products for veterinary use can be expected to be included in December 15th, 2019 and the other human medicinal products by July 15th, 2022. So that means for these product categories that the FDA and EU will still require to inspect for themselves in the other’s territory. With the completion of the MRA the EU and FDA the need for duplicate inspections may have been omitted but note that both inspectorates reserve the right to inspect in each other’s territory at any given time.
Inspecting outside their territories is also not yet operational but it is said that further guidance will be made available for this process over time. If progress is made here to rely on each other’s inspections in, for instance, China, India, and Latin America, that could significantly reduce costs further and allow the inspectorates to increase their focus on high-risk manufacturers globally.
A big question is whether importation testing and recertification will be required again for exports to the UK? Basically, if there is no mutual recognition agreement between the UK and the US (or the EU for that matter) there is a need for retesting and recertification. Obviously, this would be a significant economic cost to pharmaceutical companies located there. So, it would be in the best interest of the UK to get a Mutual Recognition Agreement in place to prevent this situation.
Blog by: Nick Veringmeier - Business Director NL