On 25 January 2023, the UK government published its response to the consultation on Point of Care (POC) manufacturing, described as personalised medicines made for the patient either within or very close to the healthcare setting. The joint consultation between 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. Those proposals were warmly received by stakeholders and steps will now be taken to introduce amendments to the legislative framework for POC manufacture and supply.
The existing framework
The majority of medicinal products are manufactured at a small number of sites and supplied globally. Unsurprisingly, the current human medicines legislation was set up with such products in mind. However, a number of highly innovative products must be manufactured and supplied at the POC, typically because they have a very short shelf life or need to be highly personalised. As it stands, there is no legal or regulatory framework that specifically covers de-centralised manufacturing, which means that on-site manufacturing, while possible, relies on the hospital having obtained the requisite licenses and having put in place the required quality, safety and traceability standards.
The European Commission maintains a flexible approach towards new manufacturing methods such as de-centralised manufacturing, but the regulatory guidance developed by the European Commission and the European Medicines Agency (EMA) provides only high-level general considerations which, we understand, will be the subject of further development and specification in the future. The EMA and Heads of Medicines Agencies (HMA) strategy to 2025 refers to the need for such guidance without any specific drafting or adoption timelines. It is our understanding that the preliminary drafting discussions are ongoing. However, the lack of clarity at EU level has led the EU Member States to take different approaches based on their own understanding and interpretation of the EU-level rules and guidance.
In the UK, post-Brexit, the MHRA has sought to address this in the current proposals.
The proposals for a new POC framework
The consultation proposed to amend the Human Medicine Regulations 2012 and the Medicines for Human Use (Clinical Trials) Regulations 2004 to create a new framework for manufacture and supply at the POC.
The new framework will be based on, and link to, the current regulatory system for medicines approvals, clinical trials, regulatory compliance at manufacturing sites and safety monitoring. The government was careful to clarify that the use of the new POC framework would not undermine the current, centralised model. The current model will represent the default option unless manufacture at the POC can be justified as essential because of the nature of the product. In addition, it will still be possible to manufacture unlicensed medicines at the POC under the ‘Specials’ regime (also known as named patient supply). However, considering the potential for manufacture at a large number of sites, the grant of an authorisation to manufacture POC products as a ‘Special’ will include new requirements within the POC framework.
The proposed framework for POC manufacturer is centred on a ‘Control Site’, which will be the only location named on the marketing authorisation. The Control Site will be required to maintain a POC Master File, which will name all of the individual POC manufacturing sites. This will be the mechanism used to authorise the sites of manufacture. The Control Site will oversee all aspects of the POC manufacturing system, including the individual manufacturing locations and their activities, and be named on clinical trial and marketing authorisation applications.
Response to the consultation
The proposals received overwhelmingly positive responses. In summary, 91% of responders agreed with the need for a new POC framework and 94% agreed with the proposed framework. In addition, there was broad support for the framework to apply across the full range of manufacturing scenarios, including modular manufacture and home-based manufacture.
Responders praised the benefits of the ‘hub and spoke’ approach encapsulated by the Control Site concept. These benefits include a proportionate and risk-based mechanism to add new manufacturing sites in order to increase capacity without the lengthy and expensive process of updating clinical trial or marketing/manufacturing authorisations.
Some responders were concerned that there would be limited or no time to conduct analytical tests after manufacture and prior to administration. The UK government said that it will use manufacturing control mechanisms that already exist in medicines regulations to address this concern. Manufacturers will need to comply with Good Manufacturing Practice, although expectations will be adapted to suit the nature of POC products. For instance, Real Time Release Testing may be more appropriate than traditional end-product testing.
In light of the proposals’ positive reception, the MHRA has started to work on a joined-up approach with other regulators within the UK and internationally, in order to facilitate the development of equivalent regulatory regimes in other territories. The UK government is taking steps to make a Statutory Instrument under the Medicines and Medical Devices Act 2021 to provide a legislative basis for the new POC framework. It says it will develop robust guidance to accompany that legislation in cooperation with stakeholders.