UK To Implement Novel Framework For Point-Of-Care Manufacturing
By Jackie Mulryne, Eftychia Sideri, and Heba Jalil, Arnold & Porter
On October 21, 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) announced that the U.K. will be the first country in the world to introduce a tailored framework for the manufacture of innovative medicines at or close to the location where a patient receives care.
A new statutory instrument was laid before the U.K. Parliament to amend the Human Medicines Regulations 2012 and the Medicines for Human Use (Clinical Trials) Regulations 2004 to provide a new regulatory framework to support the manufacture and supply of these innovative products. This includes:
- products with a very short shelf life and highly personalized medicines that mean they have to be manufactured close to the place where they are administered, known as point-of-care, or POC, products. This often applies to advanced therapy medicinal products (ATMPs) but could also be technologies such as 3D printing.
- products that are manufactured in a self-contained modular unit to enable deployment from that site to other locations, known as module manufacture, or MM, products.
This new framework follows a consultation in 2021, in which the MHRA and the Northern Ireland Department of Health sought views on legislative proposals to introduce a new regulatory framework for the manufacture and supply of POC products. The consultation received overwhelming support, where 91% of responders agreed with the need for a new regulatory framework. At present, there is no specific framework that covers decentralized manufacturing of medicines in the U.K., but as products become more innovative, and more personalized to the patient, the need for change has increased. At present, any on-site manufacturing has to rely on the hospital having obtained the requisite licenses and having put in place the required quality, safety, and traceability standards under the general framework. This leads to practical – and contractual – difficulties between the company and hospital sites.
The new framework seeks to provide the necessary regulatory oversight to ensure that POC and MM products have appropriate quality, safety, and efficacy attributes, while allowing increasing numbers of patients to benefit from these innovative products. According to the MHRA, the proposed regulation ensures that POC and MM products can be more easily made in or near a hospital setting and can get to the patients who need them safely and more quickly.
Manufacturers’ Obligations
The structure of the new framework is centered on having a control site, which will be the only location named on the manufacturer’s license. This control site will oversee all aspects of the manufacturing system, including the individual manufacturing locations and their activities, and be named on clinical trial and marketing authorization application.
The holder of the manufacturer’s license will be required to maintain a POC or MM master file (which may include an IMP master file if the product is being manufactured for a clinical trial). For POC manufacture, the POC master file will name all of the individual POC manufacturing sites and the relevant authorization and supervision mechanisms for those sites. Similarly, for MM manufacture, the master file must set out the relevant modular units.
Some of the key obligations on the manufacturer’s license holder are:
- to ensure that the medicinal products specified in the license are not handled, controlled, stored, or distributed on any premises other than the control site and those specified in the master file
- to ensure the information contained in the master file is kept up to date and is consistent with the U.K. marketing authorization for the product (where relevant)
- to record and report all suspected adverse reactions to the marketing authorization holder or sponsor.
To apply for a manufacturer’s license for POC or MM products, the applicant must supply detailed information about the product and the sites at which it will be manufactured and assembled, including:
- the location of each site at which the manufacturing and the operations are to take place
- a description of the process by which the license holder will approve and suspend new sites
- a description of the various processes at each site, including manufacturing and assembly, in addition to details of the supervision arrangements by the license holder
- contact details for people at each site who are to be contacted regarding manufacturing and assembly and quality operations under the license
- a description of the processes by which the license holder will review and amend the master file for the product.
Impact On Marketing Authorization Holders And Clinical Trial Applicants
Marketing authorization holders for medicinal products that will be manufactured using POC or MM methods must supply information to the manufacturer’s license holder so that the manufacturer can ensure the license and master file are consistent with the marketing authorization at all times.
Marketing authorization applicants or applicants for clinical trial authorizations involving such products must supply the MHRA with a copy of the master file and provide information regarding the measures put in place to ensure the follow-up of the efficacy of the product and of any adverse reactions to the product. Under GMP, the marketing authorization holder has various obligations in relation to manufacture, and the two authorization holders will need to ensure appropriate processes, information sharing, and oversight to ensure both sets of obligations are met.
Next Steps
The timing of the proposal is not clear, and the government has a long list of legislative priorities for its first year. However, the amendments could come into force in 2025. In the meantime, the MHRA is developing supporting guidance to aid the interpretation of the new regulations ahead of the legislation coming into force.
Position In The EU
Only high-level general considerations are set out in guidance by the European Commission and European Medicines Agency in relation to decentralized manufacturing and the manufacturing of ATMPs at POC. Therefore, as with the current position in the U.K., while decentralized manufacturing methods are permitted, few companies operate in this area due to the difficulties in navigating member states’ national legislation and the lack of a clear EU framework and guidance.
However, the European Commission’s proposal for reform of the EU regulatory framework for medicinal products, published in April 2023, which is currently pending adoption by the council after approval by the European Parliament in April 2024, contains proposals concerning the decentralized manufacturing of ATMPs. Similar to the U.K.’s proposed framework, a key role will be played by a central manufacturing site that will be responsible for oversight of the decentralized sites. According to the proposal, a manufacturer’s license would be required only for the central manufacturing site, subject to specific conditions.
The proposal, however, only provides high-level principles on the interactions between central and decentralized sites, and detailed guidance will be essential for companies to implement such manufacturing schemes. Further, it is still unclear to what extent the proposed legislation will be approved and/or modified by the council and by when the final legislation will be adopted.
This article was originally published as a blog post on Arnold & Porter’s BioSlice Blog.
About The Authors:
Jacqueline Mulryne is a partner on Arnold & Porter’s life sciences team. She provides regulatory, policy, and compliance advice to companies in pharmaceutical and medical technology sectors as well as cosmetics and foods. She supports companies on a broad range of issues including intellectual property rights, clinical research, market authorization, and market access strategy.
Eftychia Sideri is an associate on Arnold & Porter’s life sciences team. She focuses on EU regulatory matters affecting companies in the pharmaceutical, medical devices and food sectors.
Heba Jalil is an associate on Arnold & Porter’s life sciences team. She has acted for pharmaceutical companies in relation to a range of litigation and regulatory matters, including public inquiries regarding medicinal products and product liability litigation before the UK courts.