In July 2021, the European Medicines Agency (EMA) published the final reflection paper entitled “Good Manufacturing Practice and the Marketing Authorisation Holder” after a period of consultation with the relevant stakeholders. The document focuses on and describes the good manufacturing practice (GMP) responsibilities applicable to Marketing Authorisation Holders (MAHs). With the rise in virtual organisations, not all Marketing Authorisation Holders (MAH) are manufacturers or hold an MIA and these virtual organisations will contract out many if not all the GMP related activities.  Where the MAH is not an MIAH, they are required to appoint a competent MIAH.

The reflection paper aims to clarify and summarise the different MAH responsibilities that currently exist in the various legislation, directives and guidelines. The document is designed to assist MAHs in assuring the compliance of their medicines placed on the market.

At the outset, the paper clearly defines the MAH and Qualified Person responsibilities as stated in Annex 16 to the EU-GMP guidelines. Annex 16 provides guidance on the certification by a Qualified Person (QP) and on batch release within the European Union (EU) of medicinal products for human or veterinary use that hold a marketing authorisation (MA) or made for export. The annex also applies to investigational medicinal products (IMP) for human use, subject to conditions. As defined in Annex 16, “The ultimate responsibility for the performance of a medicinal product over its lifetime, its safety, quality and efficacy, lies with the marketing authorisation holder (MAH). However, the QP is responsible for ensuring that each individual batch has been manufactured and checked in compliance with laws in force in the Member State where certification takes place, in accordance with the requirements of the marketing authorisation (MA) and with Good Manufacturing Practice (GMP)”

This reflection paper provides clarification of the activities that may be outsourced / delegated versus responsibilities that may not.  The various MAH responsibilities detailed are summarised below:

Section 5:

  • Outsourcing and technical agreements;
  • Audits and qualification activities;
  • Communication with manufacturing sites (e.g. MA dossier information, variations, regulatory commitments, etc.);
  • Product Quality Reviews;
  • Quality defects, complaints and product recalls;
  • Maintenance of supply of medicinal products;
  • Continual improvement activities.

Section 6:

  • FMD-related responsibilities for MAHs, including responsibilities for safety features, repositories systems, serialisation data uploading and unique identifier decommissioning.

By outlining the MAH’s responsibilities in a clear and concise manner, the paper supports the role of the QP and does not change the QPs responsibilities as outlined in Annex 16.

For example:

The paper confirms the need of the MAH to provide the relevant manufacturing sites with the necessary information about MA variation approval and target implementation dates and what regulatory commitments have been agreed with the competent authorities, so that the QP at the site has full knowledge of same to for QP release.

QPs need to be satisfied with the arrangements that have been put in place by the MAH for the upload of the safety features data to the repositories system are adequate and these  responsibilities are outlined in the paper.

In conclusion, the reflection paper clarifies the responsibilities of the MAH and confirms the responsibilities of the QP.


Human Medicines, Pharmacovigilance and Committees Division Reflection paper on Good Manufacturing Practice and Marketing Authorisation Holders,  EMA/419517/2021, 23 July 2021

EudraLex Volume 4,  EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use.  Annex 16: Certification by a Qualified Person and Batch Release

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