Regulatory Update: EU/US Inspection MRA

All EU Members Have Now Joined!

BY Yuexia Li and Robert Iser - 7.31.19 -

A pharmaceutical facility current Good Manufacturing Practice (cGMP) inspection.

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:

 

Country

Name of the regulatory authority for medicinal products for human use

Date Under MRA

Slovakia 2

State Institute for Drug Control / Štátny ústav pre kontrolu liečiv (ŠÚKL)

July 11, 2019

Germany 1

Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten (ZLG)

June 26, 2019

Luxembourg 1

Minìstere de la Santé, Division de la Pharmacie et des Médicaments

June 10, 2019

Netherlands 1

Healthcare Inspectorate / Inspectie voor de Gezondheidszorg (IGZ)

June 10, 2019

Bulgaria 1

Bulgarian Drug Agency

ИЗПЪЛНИТЕЛНА АГЕНЦИЯ ПО ЛЕКАРСТВАТА

April 29, 2019

Cyprus 1

Minnistry of Health – Pharmaceutical Services

Φαρμακευτικές Υπηρεσίες, Υπουργείο Υγείας

April 29, 2019

Poland 1

The Main Pharmaceutical Inspectorate/

Główny Inspektorat Farmaceutyczny (GIF)

February 7, 2019

Slovenia 1

Agency for Medicinal Products and Medical Devices of the Republic of Slovenia

Javna agencija Republike Slovenije za zdravila in medicinske pripomočke (JAZMP)

February 7, 2019

Estonia 1

State Agency of Medicines / Ravimiamet

November 28, 2018

Belgium 1

Federal agency for medical and health products / Fedraal Agentschap voor geneesmiddelen en gezondheidsproducten/ Agence fédérale des médicaments et produits de santé

November 16, 2018

Denmark 1

Danish Medicines Agency / Laegemiddelstyrelsen

November 16, 2018

Finland 1

Finnish Medicines Agency / Lääkealan turvallisuus- ja kehittämiskeskus (FIMEA)

November 16, 2018

Latvia 1

State Agency of Medicines / Zāļu valsts aģentūra

November 16, 2018

Portugal 1

National Authority of Medicines and Health Products / INFARMED, I.P / Autoridade Nacional do Medicamento e Produtos de Saúde, I.P

September 14, 2018

Ireland 1

Health Products Regulatory Authority (HPRA)

June 1, 2018

Lithuania 1

State Medicines Control Agency / Valstybinė vaistų kontrolės tarnyba

June 1, 2018

Greece 1

National Organisation for Medicines

March 1, 2018

Hungary 1

National Institute of Pharmacy and Nutrition

March 1, 2018

Czech Republic 1

State Institute for Drug Control

March 1, 2018

Romania 1

National Agency for Medicines and Medical Devices

March 1, 2018

United States 1

Food and Drug Administration

November 1, 2017

Austria 1

Austrian Agency for Health and Food Safety / Österreichische Agentur für Gesundheit und Ernährungssicherheit (GmbH)

November 1, 2017

Croatia 1

Agency for Medicinal Products and Medical Devices / Agencija za lijekove i medicinske proizvode (HALMED)

November 1, 2017

France 1

French National Agency for Medicines and Health Products Safety / Agence nationale de sécurité du medicament et des produits de santé

November 1, 2017

Italy 1

Italian Medicines Agency / Agenzia Italiana del Farmaco

November 1, 2017

Malta 3

Medicines Regulatory Authority

November 1, 2017

Spain 1

Spanish Agency of Medicines and Medical Devices/ Agencia Española de Medicamentos y Productos Sanitarios

November 1, 2017

Sweden 1

Medical Products Agency / Läkemedelsverket

November 1, 2017

United Kingdom 1

Medicines and Healthcare products Regulatory Agency

November 1, 2017


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.


We are always available for a conversation.

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