Decentralised Medicine Manufacturing Is Getting Closer
There are some major challenges, but the new world of Point of Care (POC) manufacturing comes with exciting prospects for innovators, suppliers and patients.
Imagine a world in which healthcare looks like this: an individual feels unwell, speaks to their GP remotely and receives a prescription; they scan their prescription into their 3D printer which makes a pill, they take the pill, they feel better. It's likely to be a bit more complex than that. And, in reality, local manufacturing seems likely to be used initially only within or very close to hospitals for complex, fragile products (such as blood products and advanced therapies). There are already some interesting examples of blood products that are made and administered at speed in this decentralised manner, which have provided inspiration for the MHRA's proposals on the topic.
What is 'Point of Care' Manufacturing?
This refers to medicines that are made for an individual at or close to the healthcare setting of that individual. It might be a practical reality that the required product doesn't last very long due to stability issues, so it needs to get from the manufacturing equipment to the patient very quickly. This is achieved by, effectively, making the product at the patient's bedside.
What's Changing?
The Government considered that the current regulatory framework for manufacturers did not fit the nature of POC manufacturing and supply, which is expected to become more common. Essentially, the regulatory regime (which was designed for a centralised model of manufacturing) would not be able to handle the oversight of manufacturing activity for a single product at potentially hundreds of locations. The MHRA led a consultation on a new regulatory framework to fill that gap and avoid standing in the way of progress in this area (we covered the consultation in an earlier article).
We expect a new draft statutory instrument (SI) under the Medicines and Medical Devices Act 2021 along with MHRA guidance on the topic (including new good manufacturing practice guidance). The SI would amend the Human Medicines Regulations 2012 and the Medicines for Human Use (Clinical Trials) Regulations 2004. The MHRA have stated that the new framework will be based on and link to the existing medicines framework and adopt a similar concept to the blood products framework. In this sense, it will be a variation on a theme, rather than a completely new thing. See the MHRA's response.
Key Points to Consider
The consultation yielded generally positive results with support for the MHRA's proposals. It also led the government to confirm that it will consider modular (relocatable), mobile (within a vehicle) and home manufacturing as falling within the remit of the new framework.
The Government wants to ensure that it adopts proportionate and risk-based controls to bring about future-proof and flexible protections that are equivalent to those that apply to conventional medicines. It also wants the legislation to be enabling, and it expects guidance to be adapted as experience is gained. It is not an easy job to develop a system that will enable and react to this emerging technology and way of working and we look forward to the full legislative proposal.
The current proposed outline for the framework centres on the concept of a 'Control Site', which would be named on clinical trial authorisation and marketing authorisation applications. The Control Site would be the mechanism for authorising other subordinate sites and would be responsible for ensuring quality and other aspects of compliance. It must also maintain a POC Master File naming the other manufacturing sites. In short, a hub and spoke model.
The MHRA hopes that the new framework will pave the way for similar regulatory frameworks outside the UK, so it will be important to keep an eye on the international stage. The US FDA, for example, has published a detailed discussion paper on distributed and POC manufacturing.
The Advanced Therapy Medicinal Product (ATMP) community is watching carefully. As pointed out in a recent publication by the Advanced Therapies Treatment Centres (ATTC), it would be possible to build on the MHRA's work on POC regulation to establish a domestic manufacturing sector in the UK which would address the wider manufacturing challenges posed by ATMPs.
Contracts
A new way of working requires a new way of contracting. Here are some thoughts on the contracts expected to fall on the desk of life sciences lawyers with novel requirements relating to POC products and processes:
- Patent and know how licences - including those covering manufacturing platform technology.
- Distribution agreements.
- Research and collaboration agreements.
- POC manufacturing technology and process development agreements.
- Equipment and consumables supply agreements - including direct to consumers.
- Maintenance and facility management agreements.
- Site data management services agreements and software licences and SAAS agreements.
- Manufacturing agreements between pharmaceutical companies and Control Sites, and Control Sites and satellite manufacturing sites - will CDMOs enter this space?
- Control Site Qualified Person (QP) appointment agreements.
- QP (Control Site) to assistant QP (satellite manufacturing site) agreements.
- Pre-clinical study agreements.
- Clinical trial agreements for POC product and clinical process studies.
- Training, inspection and release services agreements.
- NHS commissioned services agreements for POC manufacturing within a hospital - and related subcontracts.
- Licence to use and occupy hospitals and other facilities - including the use of existing quality management systems.
- Product transport and medicine administration services.
- Data processing agreements covering data flows between the patient and the Control Site (and all processors in between).
- Safety data reporting agreements.
- POC manufacturing expert consultancy agreements.
An influential briefing published by UCL recommended that businesses engage early with the MHRA, suppliers and academia to prepare for the range of challenges ahead. It emphasised that companies should design clinical implementation at the same time as designing the product. The briefing also called out the need for all regulators and related organisations to prepare for the coming changes, meaning that we can expect commentary from the HTA, HRA, NICE and the HSE. UCL suggested, for example, that the HSE could develop centralised approvals for the handling of genetically modified organisms (GMO) in the POC manufacturing environment.
We would be delighted to discuss these contracts and related issues with you as we help the sector prepare for manufacturing much closer to patients.