MHRA guidance for decentralised manufacture of medicines

The MHRA has published guidance documents on the implementation of the UK's decentralised manufacture framework for personalised medicines and those with a very short shelf life. 

The suite of guidance covers issues including MA application, clinical trial authorisation and labelling, as well as good clinical, pharmacovigilance and manufacturing practice. 

The regulatory framework for decentralised manufacture (DM) was introduced into UK law on 23 January 2025 and will come into force on 23 July 2025. 

For further information on the DM framework, please see our previous article: Pioneering regulation enables manufacture of modular and point of care medicines in the UK - Burges Salmon.

What is decentralised manufacturing?

Decentralised manufacturing permits medicine production closer to the point of care, enabling highly personalised or short shelf-life medicines to be produced in smaller, modular facilities such as clinics, hospitals, or even mobile units. 

It allows for greater responsiveness to individual patient needs by reducing reliance on more traditional medical supply chains. It can also mitigate shelf life and storage issues when there is a lack of proximity between the patient and the site of medicine production. 

Overview of MHRA Guidance 

The MHRA has released seven guidance documents which we summarise below:

• The Designation Step
  • Purpose of Designation: The designation process ensures that decentralised manufacture is only used where clinically or operationally essential. The designation step confirms whether a product meets the legal criteria for Point of Care (POC) or Modular Manufacture (MM).
  • Application: Applicants must submit a justification supported by quality, and where necessary clinical, data that should demonstrate why centralised manufacturing would be inappropriate and explains how the product meets the legal test for POC or MM. A designation letter is then issued if approved. 
  • Regulatory use and validity: Before applying for a Clinical Trial Authorisation (CTA), Marketing Authorisation (MA), or manufacturing unlicenced medicines, a designation is required. If the product faces significant changes, a new designation will be needed. 
• Marketing Authorisation Application
  • The MAA should include evidence of decentralised manufacture designation. While it is not a mandatory requirement for the Control Site's Manufacturing Licence (MIA) to be appropriately scoped at submission, the applicant must provide a current and appropriately scoped Certificate of GMP Compliance in the response to the Request for Information.
• Clinical Trial Authorisation (CTA) and Good Clinical Practice (GCP)
  • Control Site: Every decentralised Investigational Medicinal Product (IMP) must have a designated Control Site that will oversee the manufacturing process and must hold a valid MIA(IMP) licence that covers decentralised manufacture. The MIA(IMP) for the Control Site is required in the CTA application dossier and the DM Master File (DMMF) should also be submitted. 
  • Quality and Validation standards: DM IMPs must meet the same development and quality standards as centrally manufactured products. 
  • Blinded Trials: For blinded DM clinical trials, sponsors must ensure that DM and administration processes don't unintentionally reveal treatment assignment. Differences in preparation time, appearance, administration, or record-keeping between active and placebo products must be carefully managed to maintain the integrity of the blind throughout trial. 
• UK Guideline of Good Pharmacovigilance Practices
  • Manufacturing Variability: manufacturing changes may be more complex for DM medicines, especially POC medicines, it is important that pharmacovigilance considers differences at manufacturing site levels well as at product and active substance level.
  • Traceability: Full traceability of product name, batch number, and manufacturing site is essential to detect and evaluate any safety concerns quickly. 
  • Risk Management and Reporting: Risk management plans must reflect the unique challenges of DM and detail how safety data will be collected and reported. Adverse reactions must be reported with product identifiers in line with existing timelines. 
  • Signal Detection and Oversight: The requirements for signal management in GVP module IX equally apply to DM products and signal detection for DM should be specific to the product as well as the active substance. 
  • Additional Monitoring: DM products will be subject to additional monitoring and the black triangle must be displayed on new products in line with the HMR 2012 regulation 202A. 
  • Safety communications and updates to product information must be timely and tailored to the DM model, ensuring accurate and up-to-date information is received by patients and healthcare professionals. 
• UK Guideline on Good Manufacturing Practice (GMP)
  • The UK-based Control Site must hold an MHRA-issued manufacturing licence and oversee all decentralised sites. The Control Site manages the DM Master File, site onboarding, training, equipment, and product release procedures. 
  • Inspections will be triggered by licence applications or variations for DM activities. Inspectors will assess quality risk management, oversight of remote sites, and the consistency of manufacturing processes amongst all locations. 
  • Product Release: For some POC products local release may happen before full analytical testing, with final certification post-administration. Traceability and robust Pharmaceutical Quality Systems must be present across all sites. 
  • Additional considerations: The guidance also discusses home-based manufacturing and the use of substances of human origin all of which require tailored risk management and regulatory compliance. 
• Labelling
  • Labelling requirements specific to the type of medicinal product and its supply status should be met. There is an exception for POC products which are required to be administered immediately (e.g. within 2 minutes of completed manufacture) and where no portion of the product will be retained. 
• Human Medicines Modular Manufacture and Point of Care regulations 2025: Overview
  • This provides a further overview of the new DM regulatory framework and is designed to assist stakeholders in understanding the scope and intent of the new legislation and navigate licencing, oversight, and safety requirements for DM manufacturing models. 

Preparing for implementation 

With just over a month to go before the centralised manufacture framework comes into force on 23 July 2025, stakeholders should ensure that they have reviewed the MHRA guidance, consider updating internal systems to meet traceability requirements, assess their licencing needs, and engage early with the MHRA to secure the required licences. 

If you have any questions regarding regulatory requirements, please contact our Health, Care and Life Sciences team. 

This article was written by Rory Trust and Amelia Hartley Baker.