Regulatory Update: EU/US Inspection MRA

The pharmaceutical facility current Good Manufacturing Practice (cGMP) inspections are the key to ensure the quality of drugs/medicines for the patients around of the world.  While it is critical for ensuring the drug product quality, it is also time consuming, and affected by many factors including regional regulations and cultural differences.  In today’s global environment, harmonizing the quality standards for manufacturing facility inspections plays an important role in securing the drug supply for patients around the world.  The Mutual Recognition Agreement (MRA) between the US FDA and European Union (EU) countries was created to meet such a role.

The Food and Drug Administration Safety and Innovation Act (FDASIA) enacted in 2012 paved the road for the MRA to become legally possible in the US.  Under FDASIA, the FDA has the authority to enter into agreements to recognize drug inspections conducted by foreign regulatory authorities, if the FDA determined those authorities can conduct inspections that meet U.S. requirements. 

In May 2014, FDA and EU started collaboration to evaluate the way they could each inspect drug manufacturers and assess the risks and benefits of mutual recognition of drug inspections.  The MRA took effect on November 1, 2017 with 9 countries as initial participants (USA and 8 EU countries).  Since then, a total of 28 EU countries and USA have joined the MRA with the last one, Slovakia joining on July 11, 2019.  A time table of when countries joined is as follow:

Information cited in this article is from:

https://www.fda.gov/international-programs/international-arrangements/mutual-recognition-agreement-mra

1. The capability determinations apply to routine surveillance inspections.  In the future the following product and inspection types may be included in the coverage of the agreement, and this is pending further consideration:

·         Vaccines for human use

·         Plasma derived pharmaceuticals

·         Investigational products (clinical trial material)

·         Veterinary products

2. Slovakia – only for inspections of chemically synthesized active pharmaceutical ingredients intended for use in drug products for human oral administration and manufactured in a dedicated, single product facility.

3. Malta - capability excludes sterile or aseptically processed drugs and biological products; and non-sterile, highly potent drug products.

It should be noted that the following are excluded from the scope of MRA:

·         human blood

·         human plasma

·         human tissues

·         human organs

·         veterinary immunologicals

Now with the MRA in-place, FDA is collaborating with the MRA participants and is reviewing their recent inspection reports and related information in determining each manufacturer’s suitability for the U.S. market in lieu of an FDA site inspection.

The benefits of MRA is apparent and plays key role in the global harmonization and standardization of the quality of manufacturing facility for producing human drugs.  Specifically:

·         The MRA provides greater efficiencies for US and EU regulatory systems by avoiding a duplication of inspections, and

·         The MRA enables reallocation of resources towards inspection of drug manufacturing facilities with potentially higher public health risks across the globe, as such, preventing low quality or even dangerous medicinal products entering into the market places.

FDA will continue to perform some inspections in EU countries with capable inspectorates, such as product specific, pre-approval inspections that support marketing approval decisions. However, FDA expects to perform fewer routine surveillance inspections in EU countries with a capable inspectorate.

The implementation of US-EU MRA is yet another great example of collaboration that creates a win-win situation for regulatory authorities globally.