By providing a clear regulatory framework for point of care medicines, the UK aims to enable increased access for patients to some of the most innovative medicines currently available, including certain advanced therapy medicinal products (“ATMPs”), radiopharmaceuticals, 3D printed products, blood products and medicinal gasses.
The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2024 ("POCAR") were laid before the UK Parliament on 21 October 2024 and, if passed, will amend the UK’s Human Medicines Regulations 2012 (“HMR”) and Medicines for Human Use (Clinical Trials) Regulations 2004 (“CTR”) to enable the manufacture and delivery of two new regulatory categories of medicine: (1) point of care (“POC”) medicines; and (2) modular manufacture ("MM") medicines.
POCAR follows a 2021 consultation with stakeholders on various proposals to support the regulation of POC medicines. The consultation received overwhelming support (91%) in favour of changes to existing regulation. With this reform, the MHRA will be the first regulator globally to take steps to modernise the current framework of medicines regulation which is predicated on centralised manufacture and subsequent distribution of medicines.
What are POC medicines?
POC medicines are those which must be manufactured on demand in the presence of, or close to, the patient. The manufacturing process for a POC medicine upends the traditional manufacturing process for most medicines, which typically involves medicines being manufactured at highly specialised GMP (Good Manufacturing Practice) sites and distributed globally.
The need for POC manufacture is growing, in particular due to the development of more ATMPs which are frequently highly personalised and have a very short shelf life.
In addition to ATMPs, POC manufacturing could be relevant to other medicinal products which are unsuited to centralised manufacture, including 3D printed products, blood products, radiopharmaceuticals and medicinal gasses.
What is Modular Manufacture?
Modular manufacture sits in the middle of the spectrum between the traditional, centralized approach to manufacturing medicinal products and POC manufacture. It involves semi-permanent or permanent manufacturing units which are either self-contained or partially dependent on a central manufacturing hub. Modular manufacturing sites will sometimes complete the "personalization" of a medicine, for example of a precision cancer immunotherapy.
As part of its 2021 consultation, the MHRA sought views on whether additional regulation for MM was necessary or whether, given that it involves manufacture primarily in a factory setting, the existing regulatory framework with new GMP guidance documents might be sufficient. The outcome is that POCAR does introduce new regulation for MM.
Current regulation
In the UK, to make or import human medicines, a manufacturing licence from the MHRA is required, which is site-specific. The manufacturer must be able to demonstrate compliance with GMP and pass regular GMP inspections. This model is not suited to individual hospitals producing medicines at POC. At present, POC medicines are generally provided as unlicensed “specials” medicines, which makes them unsuited to delivery-at-scale.
Key POCAR concepts
POCAR supplements the existing regulatory model for medicines and investigational medicinal products (“IMPs”) under the HMR and CTR with a number of concepts already used by the MHRA in other regulatory areas to provide the flexibility required for POC or MM manufacture, whilst still ensuring the quality and safety of the end-product.
POCAR introduces two new forms of Manufacturer's Licence for the manufacture of MM and POC medicinal products or IMPs.
An "MM Master File" or "POC Master File" (or, in the case of an IMP, MM (IMP) Master File or POC (IMP) Master File) will be the central document forming part of an MM or POC Manufacturer's Licence. The concept of a Master File has been adapted from existing regulation, in particular requirements for active substance master files to be included in the marketing authorisation dossier for a medicine. The applicable Master File must be maintained up to date by the holder of the MM or POC Manufacturer's Licence and will contain a detailed description of the arrangements for the manufacture or assembly of a product (with one Master File required per product). The Manufacturer's Licence holder must submit an annual update on all changes made to the Master File to the MHRA.
POCAR adopts a "hub and spoke” model, with the concept of a "control site" which is listed on the Manufacturer's Licence and individual modular units or POC sites specified in the relevant Master File. This approach is already used in the regulation of transfusions and transplants.
As with the manufacture of any medicine, compliance with GMP is key and the MHRA noted as part of the 2021 consultation that existing GMP guidelines used in the manufacture of short shelf life products such as radiopharmaceuticals would be relevant for POC medicines.
Looking forward
If passed, POCAR is subject to a six month implementation period, so will be in force by summer 2025 at the earliest. In the interim period, the MHRA intends to publish additional guidance on POC and MM manufacturing. The MHRA will also work closely with other regulators in the UK and internationally to ensure a "joined-up approach" to regulation in this area.
Pharmaceutical companies should consider whether POCAR will impact the manufacturing set-up for any existing products or could unlock new strategies and opportunities for the manufacture of pipeline products.
Whilst new legislation could provide an avenue for the wider introduction of POC medicines, questions will remain about their feasibility. In particular, amendments to the HMR and CTR will not address other issues relating to POC medicines (and ATMPs more generally), including as to funding, pricing and reimbursement, and providing adequate human and hospital resource to enable their delivery to patients.
Authored by Jane Summerfield, Bonella Ramsay, and Bea Watts.
