13/14 December 2023
Although the Mutual Recognition Agreement (MRA) is not fully in operation, the EU is already accepting FDA inspections. Already last year, the European Commission stated that the FDA "has the capability, capacity and procedures in place to carry out GMP inspections at a level equivalent to the EU." This means that EU inspectorates already accept inspections of the FDA at US sites.
But this is only one side of the coin. There will still be auditors coming from the EU to the US. The reasons are the requirements for supplier qualification in the EU-GMP legislation:
Active Pharmaceutical Ingredients (API):
Article 8 of EU-Directive 2001/83/EC defines that "the application [of a marketing authorisation] shall be accompanied […] by
So already when applying for a marketing authorisation, the respective API suppliers need to be audited (and qualified) by the manufacturer. And this is the start of an ongoing qualification.
Article 46 of the same Directive requires that (to comply with the GMP guidelines) the product manufacturer shall verify compliance of the API manufacturer it uses by conducting audits at manufacturing and distribution premises and formalised risk assessment for excipients.
Chapter 5 of the EU-GMP Guide (Production) gives more detail "… Audits should be carried out at the manufacturers and distributors of active substances to confirm that they comply with the relevant good manufacturing practice and good distribution practice requirements." [5.29]
Chapter 7 of the EU-GMP Guide (Outsourced Activities) requires that "the Contract Giver is responsible for assessing the legality, suitability and the competence of the Contract Acceptor to carry out successfully the outsourced activities" prior to outsourcing activities [7.5] and that "the Contract Giver should monitor and review the performance of the Contract Acceptor (…)" [7.7].
According to Annex 16 of the EU-GMP Guide, the Qualified Person (QP) has to ensure that "all audits of sites involved in the manufacture and the testing of the medicinal products and in the manufacture of the active substance have been carried out and that the audit reports are available to the QP performing the certification." [1.7.3]
So basically the holder of the manufacturing authorisation is responsible for the supplier qualification by law but in fact the supplier qualification is one of the duties of the Qualified Person which can be delegated to appropriately trained personnel or third parties. The compliance of the selected supplier(s) with regulatory requirements and user requirement specification should be evaluated periodically. Changes at the supplier´s site (personnel, manufacturing process etc.) that pose a particular risk to the compliance with regulatory requirements and user requirement specification should be assessed and can lead to an additional audit.