The EU’s General Pharmaceutical Legislation amendment proposal, which was published on 26 April 2023 (“the Proposal”), is introducing new measures to regulate decentralized manufacturing, which is increasingly used for certain categories of medicinal products. In particular, the Proposal introduces new obligations for manufacturers and for national competent authorities overseeing decentralized sites. In this blog, we briefly explore some of the changes introduced by the Proposal.
The Proposal acknowledges the need for decentralized manufacturing, which is of high importance especially for medicinal products such as short shelf life or autologous Advanced Therapy Medicinal Products (“ATMPs”) and other medicinal products consisting of Substances of Human Origin (“SoHO”). For these medicinal products, strategically positioning manufacturing sites in multiple locations in proximity to patients (as opposed to one central facility, where distribution is much slower and inflexible) allows for the end product to reach patients across the EU faster and in more secure way. Introducing this flexibility is intended to contribute further to creating a stable supply of medicinal products, and preventing shortages.
New obligations for Manufacturing Authorization Holders
Under the Proposal, decentralized sites do not require their own manufacturing authorization, provided they carry out their manufacturing or testing steps under the responsibility of the qualified person of a central site.
Manufacturing authorization holders of central sites must request the competent authority of the Member State in which the decentralized site is established, to register the decentralized site. A registration in the Union database, which will be created by the EMA, is then necessary to enable manufacturing activities to commence in the decentralized site. In case of medicinal products containing, consisting of, or derived from autologous SoHOs, decentralized sites have to be registered as a SoHO entity pursuant to the Proposal for a Regulation on standards of quality and safety for substances of human origin intended for human application.
Because decentralized sites do not need a manufacturing authorization, the Proposal requires manufacturing authorization applications to specify whether the site in question is a central site responsible for the oversight of decentralized sites. For each decentralized site, the central site’s manufacturing authorization application must include a written confirmation that the manufacturer has verified compliance with the Good Manufacturing Practices principles (“GMP”) through regular audits. The scope of the manufacturing activities permitted at the decentralized sites is limited to the products and operations specified in the manufacturing authorization of the corresponding central site. The Commission is expected to further detail GMP principles for decentralized manufacturing of medicinal products.
To enable national authorities to verify compliance with these rules, manufacturing authorization holders must allow the official representatives of the competent national authorities access to premises of central or decentralized sites at any time. Finally, the Proposal introduces new responsibilities for qualified persons of authorized central sites. In fact, where the manufacturing authorization is granted to a central site, the qualified person is not only responsible for the central site, but also of the quality of the medicinal product manufactured or tested at decentralized sites and its conformity to the marketing authorization.
New obligations for National Authorities
The Proposal makes the national competent authorities in which decentralized site are established responsible for both the registration and the supervision of those decentralized sites. Under the Proposal, their supervisory powers include the possibility to take the following measures:
- on-site inspections, where appropriate unannounced;
- remote inspections, when justified;
- compliance control measures; and
- the effective follow-up thereof.
These powers should be exercised in cooperation with the competent authority responsible for the supervision of the central site.
This blog is based on the wording of the EU’s proposal published on 26 April 2023. This wording could significantly change during the legislative process. Our Dublin, Brussels, Frankfurt and London teams will continue to monitor this legislation. We will be hosting a webinar to discuss the impact on 9 May. To sign up for the webinar please click here.