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EU-GMP New Annex 16: The 6 most important points

GMP Pharma - Halfmann Goetsch PartnerThe European Commission has prepared the revision of Annex 16 to the EU Guidelines for Good Manufacturing Practice for Medicinal Products „Certification by a Qualified Person and Batch Release“.

Coming into operation as of 15th April 2016, every GMP expert should be informed what matters in the new Annex 16.

Here are the six most important points that you should be aware of:

  1. 1. Why a revision of the Annex?

The Annex has been revised to reflect the increasing globalisation of the pharmaceutical supply chains and the introduction of new quality control strategies in order to prevent the entry of counterfeited medicinal products into the European market.The authorities saw the need to take this into account in the regulations.

Furthermore, the revised Annex 16 takes ICH documents Q8, Q9 and Q10 into consideration.

Last not least, the Annex 16 redefines the role of the Qualified Person and what he has to take care of personally and what he can delegate.

2. Who has the responsibility for a medicinal product?

It is clearly stated that the ultimate responsibility for the performance of a medicinal product over its lifetime, its safety and efficacy, lies within the Marketing Authorization Holder.

However, it is the Qualified Person who is responsible for ensuring that each individual batch that is being released has been manufactured in compliance with the laws in force in the Member State where the certification takes place, with the requirements of the marketing authorization and with Good Manufacturing Practice (GMP):

3. What does the batch release include?

  • The checking of the manufacture and testing of the batch
  • The quality release of the batch, which is the certification of the finished product batch performed by a QP
  • The transfer to saleable stock of the finished batch which takes into account the certification performed by a QP

The batch release is intended to ensure that the batch has been manufactured and checked according to the MA requirements, the principles and guidelines of GMP and any other relevant legal requirements.

  1. 4. What else is in the QP’s responsibility?

There are plenty of responsibilities that have to be ensured, e.g. all activities associated with manufacture and testing have been carried out according to GMP, the entire supply chain of the active substance and medicinal product is documented and available for the QP, all audits of sites involved have been carried out and reports are available, just to mention a few. (You will find the complete scope in “Certification by a Qualified Person and Batch Release”).These tasks may be delegated to appropriately trained personnel. However, the QP has to have on-going assurance that he can rely on the pharmaceutical quality systems.

  1. 5. What happens if multiple sites are involved?

Even in the case that various sites are involved in manufacture, importation, testing and storage of a batch before its certification, the QP who performs certification of the finished product batch is responsible for all stages of the manufacture of the batch. He has to ensure that all steps have gone through an agreed quality management system in order to assure GMP compliance.

He may rely on GMP assessments by third parties or share responsibility with other QPs (operating under the same or a different manufacturing authorization holder) but he has the final responsibility.

This means the QP may delegate tasks, provided that a reliable and acknowledged quality management is in place and that all intermediate steps (also storage, transport and sampling) are being controlled.

  1. 6. Is certification possible in case of unexpected deviations?

The Annex 16 states regarding the handling of unplanned deviations “Provided registered specifications for active substances, excipients packaging materials and medicinal products are met, a QP may, consider confirming compliance/certifying a batch where an unplanned and unexpected deviation from details contained within the Marketing Authorisation and/or GMP has occurred.” (3).

However, the impact of the deviation has to be thoroughly investigated and the impact should be assessed in accordance with a quality risk management process.

The Annex 16 will come into operation as of April 15


EC: Draft of Annex 16 (12 Oct 2015)

1 Comment

  1. Beril Tezcanlı on 18. July 2019 at 8:55

    If a product is produced by a CMO and released by an EU site, can we issue the site as a manufacturer instead of CMO on the packaging materials

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