EMA Addresses Globalized Supply Chain Issues with Annex 16 Revisions

Nov 22, 2011

The EMA released a concept paper for consultation on Nov. 8, 2011, that recommends a revision to Annex 16 of the Guide to Good Manufacturing of Medicinal Products to address more complicated global supply chains and new falsified medicines legislation. Since Annex 16 was introduced in 2001, a number of positive and negative trends have occurred in the pharmaceutical industry. In particular, confusion has arisen over the role of the qualified person (QP), and harmonization of requirements has been lost between member states. The EMA cites several commonly asked questions within the concept paper:

  • What is the minimum a Qualified Person (QP) must personally carry out when certifying a batch?
  • What are the prerequisites for relying on statements from persons other than fellow QPs?
  • How is the control strategy and the batch certification release process linked?
  • What are the expectations for QPs reviewing batch records manufactured by third parties in third countries?
  • What knowledge should a QP have about the site(s) involved in the manufacturing of a batch?
  • What actions are expected from the QP when a batch cannot be certified and therefore released?

A key issue is that, because of dramatic changes to the supply chain and increasing amounts of global outsourcing, QPs are no longer always personally familiar with products and manufacturing sites. Though the responsibilities of the QP have not changed since 2001, when the directives were first established, at that time the QP was normally located at the same site where manufacturing and quality control testing of the batch was undertaken. A revision to Annex 16 will attempt to ensure that, at the very least, the originally intended level of control over batches is met, and that the risk of falsified medicines is reduced. Reemphasizing the role of the QP in line with new legislation and trends (or more specifically, the extent of QP involvement versus quality systems or other personnel at remote sites), and unambiguously confirming prerequisites for certification and batch release will help achieve these goals.

With regards to importation of pharmaceutical finished product manufactured in a third country, there is a legal requirement to test each batch in the EC/EEA before certification by a QP. While the minimum requirements for testing are clear in Article 51.1(b) of 2001/83/EC for human medicinal products, the legislation is silent as to whether sampling is understood as part of the testing, which has led to different interpretations across member states. However, the EMA states in the concept paper “there is guidance in GMP Annex 16.4 and elsewhere in the GMP Guide that at least some samples are taken after importation.”

The deadline for comments on the concept paper is January 2012. A draft version of the Annex 16 guidance will be released for public consultation in December 2012, with comments welcomed until end of February 2013. Adoption of the revised guidance by the EC is planned for November 2013.