Mutual Recognition Agreement of Inspections
The EMA and FDA have been negotiating the conclusion and approval of a Mutual Recognition Agreement (MRA) since 1998. The final MRA, approved in November 2017, was based on robust data from inspections conducted by participating European Union (EU) countries that are members of the EMA and FDA. The data showed that inspection processes between agencies were comparable when conducting GMP (Good Manufacturing Practices) inspections for medicinal products for human use. The final MRA became fully applicable on 12 July 2019 for GMP inspections and batch certifications between 29 EU and US countries. The mutual recognition agreement allows the EMA and FDA to optimize their inspection capabilities and eliminate the need for multi-agency inspections. This allows patients to trust the safety, identity, strength, purity and quality of all medicines, regardless of where the products are manufactured or which authority has inspected the manufacturer. The EU, in turn, has asked the FDA to carry out 21 inspections. In addition, the FDA has postponed 172 inspections in the EU. « This allowed our investigators to inspect other high-risk areas, » Laska said. In addition, the FDA has provided the European Union with 97 inspection reports that it can use for its own compliance decisions (Figure 2). Measures to implement the agreement in all EU Member States are progressing. The expected operating date is July 15, 2019.
The mutual recognition agreement between EU and US regulators reinforces the interdependence of each other`s inspection expertise and resources. Mutual benefits for EU authorities and the FDA include: The current scope of the agreement only covers medicines for human use, with the exception of vaccines and plasma-derived products. The products covered by the agreement include: Post-MRA implementation inspections carry more weight as they are accepted by several organizations. Therefore, drug manufacturers need to gain a comprehensive understanding of the main differences between EU and US regulations. Understanding EU and US GMP regulations and inspections is now more important than ever. A « glimmer of hope, » the 2020 COVID-19 pandemic, is strengthening cooperation between regulators, according to Laska. This year alone, the US FDA requested 235 inspection reports by European authorities. 167 of these inspections were closed. The current MRA has its roots in the existing mutual recognition agreement between the European Community and the United States of 1998. « Many of you may remember that in the late nineties, some initial work on the agreement was done, but it was quickly suspended, » Laska said.
One of the many future steps of the agreement has been an important step in the evaluation of veterinary medicines The agreement does not currently apply to veterinary products, however, the EU and the FDA have agreed that veterinary medicines will be considered for inclusion by 15 December 2019 and discussions have already taken place between technical experts. On March 11, 2020, the FDA announced that it was postponing foreign surveillance inspections. On March 18, it announced that it was postponing routine surveillance inspections in the country. « The benefits of the agreements we have reached to ensure more efficient coverage of facilities shipping products to the U.S. have been remarkable, » commented Laska. « Together, Europe and the United States account for more than 80% of global new drug sales. » ( European Commission). With inspections that meet the strict standards of the EU and the US together, there is an impact on the distribution of products sold in the two largest markets. Since the locations fall under the jurisdiction of both markets, companies face tough enforcement measures if they are found to be non-compliant. Every year, EU national authorities and the FDA inspect many pharmaceutical manufacturing facilities in the EU, the US and elsewhere in the world to ensure that these sites are operating in accordance with Good Manufacturing Practices (GMP). Under the MRA, EU and US regulators will now rely on mutual inspections of medicines for human use on their own territory, thus avoiding duplication of efforts. Through the MRA, the EU and the US will be able to free up resources to inspect facilities in other countries. The pharmaceutical industry is one of the most competitive sectors in Europe and has a strong presence in many European Union (EU) countries.
The Mutual Recognition Agreement (MRA) for drug manufacturer inspections between the US Food and Drug Administration (FDA) and the EU started at the end of 2017 and was gradually extended to all EU Member States in July 2019. We quantified the number of FDA and EU GMP (Good Manufacturing Practice) inspections conducted in each territory between 2009 and 2018. The 5 EU Member States with the highest number of FDA inspections were Germany, followed by Italy, France, the United Kingdom and Spain. All of them, with the exception of Germany, have joined the group of the first 8 EU Member States to be recognised by the FDA under the MRA. In 2018, these 5 EU Member States were among the top 10 exporters of medicines from the EU to the US. Only 4 of these 5 EU Member States (Italy, Germany, France and the United Kingdom) accounted for 53.4% of total pharmaceutical production in the EU in 2018. We also examined the nature of the manufacturing operations covered by the manufacturer approvals granted by each EU Member State to manufacturers in its territory. We have demonstrated a high prevalence of conventional technology in many EU countries compared to the production of complex technologies. In the future, this imbalance should be corrected at national and EU level. For example, supporting (bio)pharmaceutical manufacturing through pharmaceutical policy initiatives, especially for EU countries with lower levels of innovation and technology, would promote the sustainability and competitiveness of these countries in pharmaceutical manufacturing. The full implementation of the MRA between the US FDA and the EU can make it faster and more cost-effective for both parties to bring medicines to market, which will improve the future competitiveness of the pharmaceutical industry in the EU and the US.
Fear. Fear. Sleepless nights. Terror of non-compliance. Do you remember the thoughts that came to your mind when you heard that a regulator would inspect your facility? And then multiply that by ten when you learned that not only did members of the U.S. Food and Drug Administration (FDA) come to inspect your facility, but inspectors from one of the member states of the European Medicines Agency (EMA) would arrive for an inspection just one week after the FDA inspection ended. Breathe deeply, life will be better! After all, signing a historic agreement between the FDA and the EMA means that these days are now behind you. EU and US compliant companies will have faster access to the markets of each other and other countries that depend on FDA and EMA inspections. Europe and the United States account for more than 80% of global sales of new medicines. However, a large part of the APIs and finished drugs are imported from countries outside their territory.
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