Measures to prevent falsified APIs

The Medicines and Healthcare products Regulatory Agency (MHRA) has published two pieces on its blog about the risk of falsified Active Pharmaceutical Ingredients (APIs) entering the supply chain and Europe-wide measures being taken to prevent this. We provide a quick guide to the key points. The blog itself can be found here: https://mhrainspectorate.blog.gov.uk/author/ewannorton/
 
The blog highlighted a number of controls which have been implemented within Europe to minimise the risk of falsification as follows.

• Registration – companies which are API manufacturers, importers or distributors need to be registered. The 2017 Orange Guide contains guidance on registration requirements.
• Inspection – the MHRA is implementing a risk-based assessment / inspection programme of all API importers and distributors (in addition to manufacturers).
• GDP requirements – the MHRA requires that all activities comply with the “Guidelines on principles of Good Distribution Practice of active substances for medicinal products for human use” (2015/C 95/01).

In respect of finished drug product manufacturers:

• Supply Chain Traceability – the holder of a Manufacturing Authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation or Clinical Trial Authorisation and do not place patients at risk. Finished drug product manufacturers must carry out regular periodic or rolling quality reviews and EU GMP Guide Chapter 1 specifically requires the review of supply chain traceability of active substances. The MHRA has confirmed that the requirement is to “fully map all the parties involved in the supply chain and periodically re-assess this for accuracy”.  This begins with the ‘active substance starting materials’ i.e. the Registered Starting Materials for the API manufacturing process.
• Registration of Suppliers - finished drug product manufacturers must check that their API Manufacturers, Importers and Distributors are “appropriately registered for all the activities they perform”.  This can be checked on the EudraGMDP website. Checks must be carried out periodically to ensure a registration has not lapsed.
• Audits of API Suppliers - EU GMP Guide Chapter 5 stipulates the regular audit of both manufacturers and distributors of active substances to confirm compliance with the relevant good manufacturing practice and good distribution practice requirements.
• QP Responsibilities - EU GMP Guide Annex 16 requires that, “the entire supply chain of the active substance and medicinal product up to the stage of certification is documented and available for the QP”. This should include the manufacturing sites of the starting materials.  All audit reports of sites involved in the manufacture of the active substance must be available to the QP performing the certification.

Stevens & Bolton’s Life Sciences team can offer regulatory advice and also has experience of pharmaceutical supply chain disputes including with API manufacturers both inside and outside the EU. For more information about the team, please contact Charlotte Tillett, Partner and Head of Life Sciences or your usual contact at Stevens & Bolton.