The new Annex 21, The Rules Governing Medicinal Products in the European Union
Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for
Human and Veterinary Use,
is now in effect. Are you prepared for it’s changes? There are a number of key requirements for a Manufacturing Import Authorisation (MIA) holder when importing medicinal products (human, IMP, veterinary) from outside the EU/EEA. While none of these are new requirements, there you may need to take action relating to your Quality System controls and records. Here are some of those changes;

Requirement for written agreements (TAs/ QTAs) – Written agreements should be in place between the site(s) performing manufacturing importation activities and the MAH of sponsor, as appropriate, in accordance with Chapter 7 of the EU GMP Guide. Have you qualified your sites of importation? Do your Supply Chain Diagrams include information on sites of importation?

Testing on importation in an EU-EEA state should cover ALL the tests needed to demonstrate that the product meets its specifications. If you are leveraging tests conducted outside the EU/EEA, you will need to engage with your regulatory agency to confirm if this will be acceptable going forward.

Imported products should be stored under quarantine after receipt until their release for further processing or following QP certification or confirmation, as appropriate. You may need to engage with your sites of importation relating to how they manage the status of your products on importation.

The documentation on the site of physical importation should include, at a minimum, the details of transportation and receipt of the product. Relevant ordering and delivery documentation should be available at the site responsible for QP certification or confirmation. See section 5.1.3 of the Annex for detailed requirements.  These records should be available to the site of certification or confirmation to support batch disposition.

PQRs: Where sampling of the imported product is conducted in a third country, the PQR should include an assessment of the basis for continued reliance on this sampling practice. PQRs should also include a review of deviations re transportation up to the point of batch certification. Specific requirements for sampling and transportation of imported products are detailed further in Annex 16 of the EU GMP Guide. The analytical results from importation testing should be compared with those in the CoA generated by the third country manufacturer. Any discrepancies or out of trends (OOT) should be documented and investigated.

The final reminder is the responsibility of the site for QP certification to ensure that an ongoing stability program is in place, as required under Chapter 6 of the EU GMP Guide.

If you need more guidance following the updated Annex 21, do not hesitate to contact us here