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Commencement of operational phase of the EU – US mutual recognition agreement on inspection of manufacturers of medicines

News Category: Regulatory news

Date: 08/03/2018

Please see update from 1 June 2018
 
The HPRA welcomed the commencement, on the 1st November 2017, of the operational phase of the mutual recognition agreement (MRA), between the European Union and United States, on inspection of manufacturers of medicines. When fully operational it will mean that the outcomes of inspections of manufacturers of medicines will be mutually recognised and only in exceptional circumstances will one party carry out an inspection in the territory of the other. 

Scope of MRA

(Mutual Recognition Agreement)

  • The initial scope includes human medicines, which incorporates intermediates and in-process materials, certain biological products and active pharmaceutical ingredients (APIs). 
  • Veterinary medicines are not included at this time but a decision on their inclusion will be made no later than mid-July 2019.
  • Certain human medicines, including vaccines and plasma derived medicines, are not included at this time but could be added (a decision on this will be made no later than mid-July 2022).
  • Veterinary immunologicals are excluded as, in the US, these are regulated by its Department of Agriculture rather than the US Food and Drug Administration (FDA) which regulates all other human and veterinary medicines.

 

Current status

  • Batch testing on importation from the US will continue until the capability of all EU authorities has been assessed by the FDA, i.e. until July 2019.
  • Prior to the 1st November 2017, the EU had assessed the good manufacturing practice (GMP) inspection system of US FDA and was satisfied that it was equivalent to that operated by EU competent authorities.   
  • The FDA has been working in the EU to assess the capability of the GMP inspection system of each of the human medicines competent authorities. This is a considerable task and will be completed in stages up to July 2019.
  • As part of this due diligence, the FDA has been observing audits carried out under the EU Heads of Medicines Agencies (HMA) Joint Audit Programme (JAP). As the FDA is reliant on the JAP schedule in the EU, there is no particular order or prioritisation to its evaluation of member state competent authorities. By the 1st November 2017, as required under the terms of the MRA, the FDA had completed the capability assessment for eight competent authorities in the following member states:  Austria, Croatia, France, Italy, Malta, Spain, Sweden, and United Kingdom. On the 1st March 2018 an additional four competent authorities in the following member states were added: Czech Republic, Greece, Hungary, and Romania

  • The agreement includes other milestones for the FDA’s completion of capability assessment on further competent authorities, i.e

      • 01/06/2018 -  2 additional assessments
      • 01/12/2018 -  6 additional assessments
      • 15/07/2019 -  8 additional assessments

       

  • For further details on the capability assessment see Appendices 4 and 5 of the MRA.

 

FDA’s assessment of the HPRA

The audit of the HPRA’s GMP inspection system under the JAP took place during the week of 15th May 2017 and was observed by the FDA. A number of documents were provided to the FDA in mid-November by the HPRA as part of the formal capability assessment. We’ve recently been informed that the capability assessment of the HPRA has commenced. 

What’s happening in practice?

  • At present, the outcomes of FDA inspections of US based manufacturers of human medicines falling within the scope of the MRA are recognised by all EU member state competent authorities for human medicines.
  • The FDA recognises and accepts GMP documents relating to the outcomes of inspections of manufacturers that fall within the scope of the MRA. This currently applies to inspections that have been carried out by the competent authorities of the eight named member states within their own territories.
  • Where the FDA has yet to complete its capability assessment of a member state competent authority, it may carry out an inspection of a manufacturer of human medicines based in that country.
  • For manufacturers of medicines (human or veterinary) that are outside the current scope of the MRA, inspections by each party in the territory of the other will continue.

 

Useful links

 

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