Since 23 July 2025, manufacturing of medicines at the Point-of-Care (POC) and Modular Manufacturing (MM) have been possible in the United Kingdom, following the entry into force of the new legislation establishing the Decentralised Manufacturing (DM) framework (The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2025).
The new regulatory framework developed by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) is the first worldwide to address the need to manufacture personalised therapies as close as possible to the patient while providing the usual quality, safety and efficacy standards of centralised production. The implementation of the new Decentralised Manufacturing legislation was supported by a cross-agency team comprising of Quality and Clinical Trial assessors, Safety and Surveillance assessors, Inspectors for Good Manufacturing Practice (GMP), Pharmacovigilance (PV) and Good Clinical Practice (GCP) plus scientists from the MHRA Science Campus.
The issue was also included in the 2023-2024 working programme of the EMA’s Quality Innovation Group, alongside continuous manufacturing of biologicals and end-to-end continuous manufacturing. The MHRA also shared at the ICMRA Workshop on Decentralised or Distributed Manufacturing, that took place in December 2024, its experience of setting up the new framework. The outcomes of the meeting are expected to support the future publication of harmonised regulatory documents on decentralised manufacturing by other international authorities.
Cut times and provide better access
The two main objectives of the UK’s decentralised manufacturing framework are to significantly reduce the time needed to produce personalised innovative treatments for individual patients, without for example having to collect and forward their cells to a hub center for engineering. The ability to manufacture small or individual batches of therapy products in a matter of days rather than weeks or months will also reduce hospitalisation, thus providing a broader number of patients with access to innovative treatments. Medicinal products covered by the new framework include cell and gene therapies, tissue-engineered treatments, 3D printed products, blood products, and medicinal gases.
According to the new regulations, the final manufacturing steps for personalised or time-sensitive treatments such as, for example, antitumour CAR T therapies, can now be performed directly in hospitals, ambulances or local care settings in the UK, on the basis of clear, regulated protocols. If patients are unable to travel to the hospital due to compromised health conditions, the new framework also allows for mobile manufacturing units to be installed close to the patients’ homes or local care settings. This reflects the the aim of expanding the “hospital at home” programme, which is part of the NHS’s “10 Year Health Plan for England”.
The MHRA has opted for a “hub and spoke” model for decentralised manufacturing. A central Control Site provides detailed instructions on how to proceed and monitors overall processes to ensure compliance with procedures, patient safety and the efficacy of the locally manufactured products. The new processes will be an option and will be subject to the same GMP requirements as centralised manufacturing, that will remain the standard model.
Justification for decentralised manufacturing must be clearly linked to a clinical benefit; cost-only justification is not acceptable. In particular, the Control Site must have a dedicated licence and be responsible for generating and managing the Decentralised Manufacturing Master Files (DMMFs). Central hubs may also be inspected by regulatory authorities.
To optimise the development process and support the obtaining of marketing authorisation for decentralised or modular manufacturing, interested companies can access the MHRA’s scientific advice at any stage of product development. Various guidelines covering different aspects of decentralised manufacturing are also available on the MHRA’s Decentralised Manufacture Hub webpage. These guidelines should be read alongside existing guidelines. Initially drafted by the MHRA, the guidelines were then finalised according to comments raised during a dedicated workshop. The Designation step is a particularly critical part of the application process, as it requires the MHRA to assess whether the legal requirements for Point-of-Care or Modular Manufacture have been met.
The first considerations on requirements for DM
The MHRA has published a first set of considerations to help stakeholders understand the new procedures.
Applications for decentralised manufacturing can only be submitted by applicants with a legal presence in the UK. The new framework is a “scale out” option, opposite to the usual “scale up” model used for the large-scale, centralised manufacturing of medicinal products characterised by long term stability.
The development of the DM framework was based on three distinct pillars. From a regulatory perspective, the MHRA has developed and made available all the necessary technical and procedural guidance documents, which will be updated in line with the experience gained from the new processes and the emergence of new regulatory issues. Institutionally, the MHRA collaborated with various healthcare providers to set up the new system, including the National Health Service (NHS) and its Specialist Pharmacy Service, the Human Tissue Authority (HTA) and the National Institute for Health and Care (NICE).
The suitability of a decentralised manufacturing location should be jointly evaluated by the applicant and the relevant healthcare provider. Technical considerations for evaluating the suitability of a location for DM include manufacturing complexity, environmental conditions requirements and automation availability.
A wide range of technologies
Decentralised manufacturing can be used in the UK to provide Point-of-Care services to patients. These include products that require particular attentions with respect to the manufacturing process, the shelf life, the characteristics of constituents or the method or route of administration. The new framework can be applied to all dosage forms, whever they are new products or existing centrally-manufactured ones, they are at the clinical trail stage or already authorised.
Point-of-care technologies may refer to the provision of temporary manufacturing capabilities to meet intermittent or occasional clinical demand. In such instances, a contract service providing access to mobile PoC manufacturing technologies could be the optimal solution for healthcare providers, similar to the way mobile MRI or CT scanners are used.
Another possible application of PoC manufacturing is to make products available only when needed, for example during a surgical procedure or while patients are being treated at an intervention on the ward. Alternatively, products that have been manufactured at a stable intermediate stage can be delivered to the patient’s home. Final PoC manufacturing can then follow once clinical authorisation to complete the manufacturing process is available.
On the other hand, modular manufacturing enables the rapid production or assembly of the target products within a self-contained modular units located as close as possible to the patient. This approach could be particularly useful if the patient requires conditioning prior to receiving the innovative therapy, as in the case with personalised cancer treatment.
Another possible application of modular manufacturing is the rapid deployment of pandemic vaccines, particularly in the early stages of a pandemic when the fill-finish capacity may still be limited, storage conditions may be an issue, or regional manufacturing may be limited.
