After a public consultation last July, the EMA published its Reflection Paper on Good Manufacturing Practice (GMP) and Marketing Authorisation Holders (MAH) on 23 July 2021. The Paper aims to clarify the responsibilities of the MAH in the GMP guidelines and the applicable legislation. While it is not legally binding, the EMA expects competent authorities to use the Paper as guidance when performing inspections, and so MAHs should familiarise themselves with the document. In this blog we have summarised the key takeaways.
What does the Paper reflect upon?
Whilst MAHs often do not engage in manufacturing activities directly, the Paper reminds MAHs that they bear the ultimate responsibility for compliance with the regulatory obligations imposed on them in respect of manufacturing activities, even where the tasks are delegated to an affiliate or outsourced. The Paper sets out a non-exhaustive lists these obligations in Sections 5 and 6, grouped into under different themes, as follows:
- 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; and
- Continual improvement activities.
- Falsified Medicines Directive (FMD)-related responsibilities for MAHs such as for safety features, repository systems, serialisation data uploading and unique identifier decommissioning.
The Paper confirms that delegation of tasks or activities is possible and indeed sometimes necessary in complex supply chains. However, it states that any delegation needs to be in writing, as outlined in Chapter 7 of the GMP Guide which requires that “any activity that is outsourced should be appropriately defined, agreed and controlled in order to avoid misunderstandings which could result in a product or operation of unsatisfactory quality.” This requirement is likely to require many MAHs to revisit their intra company documentation, to ensure that delegated tasks are appropriately documented. There is no requirement beyond ‘in writing’, but it would be prudent to have such obligations in a written agreement, especially given the MAHs wide-ranging responsibilities that remain intact when delegating.
What should I do now?
The Paper increases the likelihood of adverse inspection findings based on MAHs and the companies to whom they delegate tasks not having appropriate documentation in place.
MAHs should therefore review their supply chain structures to ensure they have technical agreements in place to govern any delegated tasks and activities. The agreements should offer the MAHs sufficient oversight and ability to intervene if needed.