MHRA’s Decentralized Manufacturing Regulation Set to Take Effect

The United Kingdom’s regulatory authority, the Medicines and Healthcare products Regulatory Agency (MHRA), has introduced amendments to the Human Medicines Regulations 2012 that will bring medicines closer to the patient through decentralized manufacturing (DM).

The amendment to the regulation was signed into law through a statutory instrument (SI) on January 23, 2025 (1). The amended Human Medicines Regulation and the Medicines for Human Use (Clinical Trials) Regulations 2004 will take effect July 23, 2025, supporting the manufacture of medicine at the point of care (POC) as well as modular manufacturing (MM) (2).

Notably, DM will create flexibility for manufacturers while enabling the maximum number of patients to access the medicines they need, when they need them, in a safe and timely manner (3).

The amendment applies to a wide range of pharmaceutical dosage forms, including medical gases, biological, biotech, blood, small molecule, and advanced therapy medicinal products (ATMPs).

What Are POC and MM?

Medicines manufactured close to the patient (for example, at the bedside) for immediate administration are classified as POC. In general, this allows medicinal products—typically those with a short shelf life or that are highly specialized—to be made and administered at or close to a patient’s location.

Manufacturers intending to obtain a POC license will need to provide evidence to the MHRA that their product “can only be manufactured” at or near the place where the product is to be used or administered (4). The MHRA must also agree that the product meets the legislative requirements.

MM can include any activities performed away from traditional manufacturing sites (for example, at a clinic or hospital laboratory) to enable deployment to other locations. The flexibility to move manufacturing facilities allows medicines to be closer to patients and accessed faster. This can be important when rolling out vaccines or in a military field environment. To qualify for the MM license, the agency has taken a broader approach that is not limited to starting materials or short shelf life, but the rationale must support scaling out rather than scaling up. The MHRA will be looking for justification based on product deployment—for example, early rollout during a pandemic (3,5).

Each product will have a DM master file (DMMF) that captures the locations, status of manufacturing sites, contact details, products, processes, and procedures (3).

How Can Manufacturers Obtain POC or MM Licenses?

During an MHRA webinar on decentralized manufacturing, the agency provided guidance on the designation process (3). Applicants are encouraged to apply early or once data indicate their product will meet the relevant DM designation criteria.

The application must provide background information about the product and justification for why the proposed product meets the legal basis. Applicable fees will be based on scientific advice. The MHRA will issue a decision on DM designation within 60 days if no additional information or meeting is required. If a meeting or further information is needed, the applicant can expect to receive the designation decision within 90 days (4).

Manufacturers that already hold other licenses—such as manufacturing and import authorizations (MIA), MIA investigational medicinal products (IMPs), or manufacturing specials (MS)—can submit a variation to add the POC or MM licenses to their existing license. According to the MHRA, an application will trigger an inspection that will assess the systems and controls in coordination with the DMMF (3).

Manufacturer Obligations

All DM products are required to have a control site, which is the only site listed on the manufacturer’s authorization. Individual secondary sites will be authorized by being included in the DMMF. Manufacturers are not required to submit a variation to notify the MHRA of new or decommissioned sites; however, they must notify the MHRA of any material alteration to the control site or modular units (2). License holders must maintain the DMMF and keep it up to date with annual reporting of updates and changes.

In addition to these general requirements, there are specific obligations that license holders must follow:

Labeling

Labeling requirements will follow the standard requirements of a marketing authorization. However, there is a labeling exemption for medicines manufactured for immediate administration at the POC, with no portion of the medicinal product being retained after administration. In such cases, the use of “pre-applied patient identified” on the primary packaging is recommended (2).

Qualified Person Release

Although the Qualifies Person (QP) can nominate an individual who is independent of the manufacturing and clinical team of the patient in question to release a POC product, the license holder must demonstrate how they will ensure consistency in the release process and how the process will be reviewed, including how the QP will maintain oversight (4).

Pharmacovigilance and Clinical Trial Use

Throughout the product’s lifecycle, manufacturers are expected to demonstrate how they will maintain product and batch traceability. To demonstrate traceability, manufacturers must show the integration of several healthcare settings, particularly those involved or used for the DM product.

Manufacturers are required to have a robust process in place to show how adverse events (AEs) are collected, allocated, and evaluated, including oversight of contracts and agreements. Decentralized medicines, including the control and manufacturing site lists, will be included in the pharmacovigilance system master file (PSMF). The license holder must also demonstrate how the qualified person for pharmacovigilance (QPPV) maintains oversight of the process and sites, and how the process links to other personnel or departments such as the responsible person (RP) or quality department (2).

The MHRA will focus on the processes and their management. For example, if there is an issue at one of the sites, how will the license holder know whether it is an isolated incident or whether multiple sites are affected? What processes are in place to manage such situations?

Similarly, for clinical trials, there is emphasis on how risks are identified, managed, and mitigated. Manufacturers must demonstrate how the investigator maintains oversight of the investigational medicinal product (IMP) activities at remote sites and how blinding of treatments is managed (2).

Although manufacturers’ obligations are similar to those in a traditional manufacturing environment, there will be greater emphasis on risk minimization and whether a manufacturer can demonstrate oversight of all processes—from manufacturing and product traceability to adverse events.

Conclusion

DM is designed to ensure that patients can access innovative medicines that are not easily deliverable in a traditional, centralized manufacturing setup. The development of new guidance underscores the MHRA’s commitment to a patient-first approach, allowing access to treatment where and when it is needed without compromising quality.

As treatment methods continue to evolve and experience with DM increases, it is likely that the guidance will change over time.

How well do you understand the amendments, how they will affect manufacturing practices, and what will be required to meet DM objectives? We would like to hear what these changes will mean for you.

References

1. The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2025. UK Statutory Instruments, 2025 No. 87. https://www.legislation.gov.uk/uksi/2025/87/contents/made
2. “Statutory instrument laid in Parliament provides first regulatory framework of its kind that will transform the manufacture of innovative medicines at the point of patient care.” GOV.UK. https://www.gov.uk/government/news/statutory-instrument-laid-in-parliament-provides-first-regulator
3. Decentralized manufacture hub. GOV.UK. https://www.gov.uk/government/collections/decentralised-manufacture-hub
4. Decentralized manufacture: The designation step. Medicines and Healthcare products Regulatory Agency. June 10, 2025. https://www.gov.uk/guidance/decentralised-manufacture-the-designation-step
5. The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2025. GOV.UK