On 16 November 2018, the United States (US) Food and Drug Administration (FDA) confirmed the capability of the Danish Medicines Agency to carry out Good Manufacturing Practice (GMP) inspections at a level equivalent to that of the FDA, which adds Denmark to the list of recognised countries under the Mutual Recognition Agreement between the European Union (EU) and the U.S.

Factual background

The Mutual Recognition Agreement between the EU and the US was adopted in 1998. The agreement included a Sectoral Annex on Pharmaceutical Good Manufacturing Practices, which allowed EU and US regulators to rely on each other’s GMP inspections. However, this part of the agreement was never fully implemented.

Based on the 1998 Mutual Recognition Agreement, negotiations between the EU and the US continued in regard to the Sectoral Annex. Finally, in June 2017, the European Commission confirmed its acceptance and recognition of FDA’s capability, capacity and procedures to carry out GMP inspections at a level equivalent to that of the EU.

Shortly after, in November 2017, the FDA confirmed the capability and recognition of the national food and drug authorities of eight EU member states. Subsequently, in November 2018, Denmark and five other member states were added, and the number of recognised member states is gradually expanding. The FDA plans to assess each EU member state’s authority individually, and accordingly a transition phase will be in place until July 2019. Meanwhile, the agreement is intended to be operational in all EU member states by 15 July 2019. For the time being, the FDA relies on a total of 24 local authorities in the EU to replace their own inspections.

Purpose of the Mutual Recognition Agreement

The main purpose of the Mutual Recognition Agreement between the EU and the US is to strengthen reliance on each other's inspection expertise and resources of the pharmaceutical companies that manufacture classic human medicines and to share information on, for instance, quality issues identified on local manufacturing sites. The agreement also entails that the EU and the US recognise each other's regulations of the GMP of drugs.

The mutual benefits for EU authorities and the FDA in respect of reliance on each other’s inspection expertise include:

  • the ability to focus inspection resources on other parts of the world where active pharmaceutical ingredients and medicines for the EU or US markets are manufactured;
  • priority of inspections of medicines manufacturing sites for higher risk cases;
  • reduction of costs and administrative burden from duplicative regulatory inspections of pharmaceutical manufacturers, including smaller manufacturers.

Moreover, the pharmaceutical industry in general will benefit from the agreement. As Denmark has an extensive pharmaceutical production, and since the US is a significant export market for Denmark, the FDA has made frequent and extensive inspections at Danish manufacturing sites. With the FDA’s recognition of the Danish Medicines Agency, Danish pharmaceutical companies will avoid duplication of work relating to the authorities' inspection at manufacturing facilities.

Scope of the Mutual Recognition Agreement

The current scope of the amended Sectoral Annex of the Mutual Recognition Agreement covers a broad range of human medicines and medical products including:

  • human chemical pharmaceuticals;
  • medicinal gases;
  • human biologicals, including immunologicals and biotherapeutics;
  • human radiopharmaceuticals;
  • homeopathic medicines if classified as medicinal products;
  • vitamins, minerals and herbal medicines if classified as medicinal products;
  • active pharmaceutical ingredients;
  • intermediate products and bulk pharmaceuticals.

Products excluded from the scope of the agreement are:

  • veterinary products
  • human blood and plasma;
  • human tissues and organs;
  • veterinary immunologicals;
  • advanced therapy medicinal products.

The operational scope of the Mutual Recognition Agreement is expected to expand gradually. Veterinary products will be considered for inclusion by no later than 15 July 2019 and human vaccines and plasma-derived medicines will be considered for inclusion by no later than15 July 2022.

Products intended for use in clinical trials (investigational medicinal products) will be considered for inclusion at a later stage. These products will be covered on condition that they are inspected by the FDA.