Agreement now operational between 12 EU Member States and FDA

The mutual recognition agreement between the European Union (EU) and the United States (US) to recognise inspections of manufacturing sites for human medicines conducted in their respective territories is progressing as planned. Today, the US Food and Drug Administration (FDA) confirmed the capability of four more EU Member States (Czech Republic, Greece, Hungary, and Romania) to carry out good manufacturing practice (GMP) inspections at a level equivalent to the US. There are now a total of 12 Member States whose inspection results the FDA can rely on to replace their own inspections.

Plans for the agreement to be operational in all EU Member States by 15 July 2019 are on track.

The agreement is underpinned by robust evidence on both sides of the Atlantic that the EU and the US have comparable regulatory and procedural frameworks for inspections of manufacturers of human medicines. Teams from the European Commission, EU national competent authorities, the European Medicines Agency (EMA) and the FDA have been auditing and assessing the respective supervisory systems since May 2014, and are working closely together to reach the agreement's milestones.

In June 2017, the European Commission confirmed that the FDA has the capability, capacity and procedures in place to carry out GMP inspections at a level equivalent to the EU. Since 1 November 2017, EU Member States can rely on inspection results from the FDA to replace their own inspections. On 1 November 2017, the FDA confirmed the capability of eight EU Member States (Austria, Croatia, France, Italy, Malta, Spain, Sweden, and United Kingdom). The assessment of four more EU Member States by 1 March 2018 as planned reaffirms that the timetable for assessment of all remaining inspectorates before 15 July 2019 can be met.

Each year, EU national authorities and the FDA inspect many manufacturing sites of medicines in the EU, the US and elsewhere in the world, to ensure that these sites operate in compliance with GMP. Around 40% of finished medicines marketed in the EU come from overseas and, for around 85% of medicines sold in the EU, at least one manufacturing step takes place outside the Union.

The mutual recognition agreement between EU and US regulators strengthens reliance upon each other's inspection expertise and resources. Mutual benefits for EU authorities and the FDA include:

relying on each other's inspections and hence avoid duplication. To this effect, information is being continuously exchanged, including most recent and upcoming GMP inspections of manufacturing sites;

a better use of their inspection resources to focus on sites of higher risk where active pharmaceutical ingredients and medicines for the EU or US markets are manufactured;

reassuring patients that they can rely on the quality, safety and efficacy of all medicines, no matter where they have been 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.

Whilst veterinary medicines are not immediately included in the operational scope of the agreement, they will be considered for inclusion by no later than 15 July 2019. Discussions to this effect have been initiated between experts on both sides.

Background to the MRA agreement

To make the agreement operational, the EU and the US need reassurance that the GMP inspectorates on both sides have the capability, capacity and procedures in place to conduct inspections and to supervise manufacturing sites of medicines at an equivalent level. In September 2015, EU officials visited three FDA field offices, FDA's headquarters in Silver Spring, Maryland, and an FDA laboratory as part of its assessment. The EU team applied the same criteria that it applies within the EU when it audits its own Member States.

The EU invited the FDA to observe the internal EU audits of the inspectorates of each Member State performed as part of the joint audit programme. These audits aim to ensure consistency across all EU inspectorates by assessing processes, workforce skills and compliance with EU laws and relevant guidelines. To date, the FDA has observed the audits of inspectorates responsible for human medicines of almost all EU Member States.

After observing the audit of a country's inspectorate, the FDA conducts an independent assessment that includes a review of the country's conflict-of-interest policies, samples of inspection reports, inspector training records, inventory of drug manufacturing facilities, surveillance program and numerous standard operating procedures.

In the EU, inspections of manufacturing sites are carried out by national competent authorities from EU Member States. EMA plays an important role in coordinating these activities in collaboration with the Member States.