Annex 16 QP Certification: important Questions and Answers

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29/30 March 2023

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What can a Supply Chain Diagram look like? How to rely on vendor-supplied samples? These are just two examples of questions being frequently asked in connection with the new Annex 16 of the EU-GMP Guidelines (Certification by a Qualified Person and Batch Release).

The new Annex came into force in April 2016 with quite a few new requirements and expectations. And it is still causing some uncertainty. Some of the major questions have now been answered in a blog of the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) Inspectorate.

For example, the new Annex 16 makes clear that "samples may either be taken after arrival in the EU, or be taken at the manufacturing site in the third country in accordance with a technically justified approach which is documented within the company's quality system." But how should this Pharmaceutical Quality System be used to support reliance on the vendor-supplied samples? This question is the first one to be answered in the blog:

"This could be similar to a typical vendor assurance programme for the qualification of a new vendor. For example, comparative analysis of samples taken in the third country and further samples taken after importation should be tested together, until a justification can be supported to rely on third country samples only. There should be assurances (through audit and technical agreement) that the manufacturing site takes the samples according to approved procedures, and that the samples are random and representative of the entire batch" (…), MHRA says.

Answers to other questions discuss the timing of comprehensive scientific studies, comparative analysis and how "a review of any unexpected result or confirmed out of specification result could be performed".

Annex 16 also requires the mapping of the supply chain: "The entire supply chain of the active substance and medicinal product up to the stage of certification is documented and available for the QP. (…) The document should preferably be in the format of a comprehensive diagram" (1.7.2). Now, with this blog, an example of such a supply chain diagram is provided to support the understanding of the supply chain and to "avoid any misinterpretation that can be caused by bulky documentation".

The complete set of frequently asked questions can be found in part 1 of the MHRA blog.