EU GMP Non-Compliance Report might lead to FDA Import Stop in future

The new MRA Agreement between the EU and the USA on the mutual recognition of GMP inspections is being discussed in depth. One shouldn't conclude though that the inspection pressure would decrease now because of the recognition of EU inspections. There is a series of exceptions to look out for. The FDA will first ask the competent authority of the EU when the last GMP inspection was performed at a site in question and which GMP deficiencies were found. If no recent inspection report is available (e.g. the inspection hasn't been performed recently), the FDA can either request a further inspection (Article 10) or perform an inspection itself. In the MRA Agreement, Article 11 states: "Within 15 calendar days of receipt of the request, the recognized authority shall acknowledge receipt and confirm whether it will conduct the inspection in accordance with the requested timelines"... further, it is stated that: "For greater certainty, if the recognized authority indicates that it will not conduct the inspection, the requesting authority has the right to conduct its own inspection of the manufacturing facility and the requested authority has the right to join the inspection."

Beside the fact that the FDA will perform its own inspections in the cases mentioned above, the future consequences of an EU GMP inspection for the US market should also be considered. Article 8 "Recognition of inspections" states: "For purposes of this Annex, to accept an official GMPs document means to rely on the factual findings in such document." A GMP Non-Compliance Report is also an official GMP document. If an EU authority declares a GMP Non-Compliance status - among other things in the EudraGMDP - the FDA will use this assessment and take measures against the facility in question. In some cases, those measures might lead to an import alert, in other words to an import stop for the US market.

There are still substantial questions with regard to which EU GMP inspectorates will be recognised as of the 1st of November, for there is no list with the recognised authorities yet. According to Article 19: "If, by 1 November 2017, the FDA has not completed assessments under this Annex of at least eight Member State authorities for human pharmaceuticals listed in Appendix 2, despite having received complete capability assessment packages from those authorities as specified in paragraph II.A.1 of Appendix 4 in accordance with the schedule set out in Appendix 5, application of the Articles referred to in paragraph 2 shall be postponed to the date on which the FDA has completed assessments of at least eight such authorities."

Regarding Germany, the Annex has a surprise too. Indeed, the German Federal States are responsible for GMP supervision. Although a coordinating body (ZLG) exists, the responsibility for GMP monitoring lies solely with the Federal States. Nevertheless, the Agreement provides that not the Federal inspectorates but the following authorities be assessed by the FDA:

• Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) - Federal Institute for Drugs and Medical Devices
• Paul-Ehrlich-Institut (PEI) - Federal Institute for Vaccines and Biomedicines
• Bundesministerium für Gesundheit (BMG) - Federal Ministry of Health / Central Authority of the German Länder for Health Protection Regarding  Medicinal Products
• Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL) -  Federal Office of Consumer Protection and Food Safety
• Federal Ministry of Food and Agriculture