20/21 October 2021
In January 2020, the European Medicines Agency (EMA) published a draft of a so-called reflection paper entitled "Good Manufacturing Practice and the Marketing Authorisation Holder" and invited comments from stakeholders. Now the final document has been published. The content of the document is GMP responsibilities that apply to Marketing Authorisation Holders. As not all Marketing Authorisation Holders (MAH) are also manufacturers and have a Manufacturing/ Import Authorisation (Manufacturing/ Import Authorisation Holder, MIAH), the aim here is to provide clarity on the different responsibilities and their practical significance for MAHs. Ultimately, the aim was to summarise and, if necessary, explain in one document the responsibilities that are described in various places in the relevant GMP documents such as the EU-GMP Guidelines or the respective Directives.
It is important to note that the title of the reflection paper is "GMP and Marketing Authorisation Holder", not "GMP for the Marketing Authorisation Holder". So far, EU legislation does not require demonstrable GMP competence for pure MAHs. However, the reflection paper describes several GMP responsibilities of the MAH. Since the MAH has the ultimate responsibility for the product, the MAH should consequently also be responsible for GMP compliance. The MAH is therefore obliged to appoint at least one MIAH with appropriate authorisation and competence. While many MAHs are also MIAHs with proven GMP competence, many MIAHs are little more than a registered office somewhere in the EU without any manufacturing activities.
Documents published by EMA fall into a number of defined categories depending on their intended purpose. The following is extracted from the Procedure for European Union Guidelines and Related Documents within the Pharmaceutical Legislative Framework, published by EMA 18 March 2009:
"A reflection paper may be developed to communicate the current status of discussions or to invite comment on a selected area of medicinal product development or a specific topic. It can provide a framework for discussion or clarification particularly in areas where scientific knowledge is fast evolving or experience is limited. A reflection paper does not provide scientific, technical or regulatory guidance, but may contribute to future development of such guidelines, or related document."