MHRA releases spate of new guidelines on decentralized manufacturing

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) on Tuesday released six guidelines to clarify expectations and support the new regulatory framework for decentralized manufacturing (DM), which takes effect on 23 July 2025.

The guidelines implementing the modular manufacturing and point of care legislation encompass several key areas: applying for DM designation, the procedure for obtaining marketing authorization for the DM, the clinical trial authorization (CTA) for DM, good pharmacovigilance practices, the application of good manufacturing practices (GMP) for DM, and labeling requirements.

MHRA is one of the few regulatory agencies in the world to have established a regulatory framework for decentralized manufacturing. In September 2024, the US Food and Drug Administration (FDA) finalized a guidance on decentralized clinical trials, but the guidance did not address decentralized manufacturing. (RELATED: FDA’s final guidance on DCTs adds clarity on HCP task log, inspection requirements, data variability, Regulatory Focus 17 September 2024)

In October 2022 FDA published a discussion paper on point-of-care (POC) and decentralized manufacturing; but has not issued any guidance on the topic. (RELATED: FDA releases discussion paper on distributed and point of care manufacturing, Regulatory Focus 14 October 2022).

According to MHRA, decentralized manufacturing can refer to two modes of manufacturing, as defined by its decentralized manufacture hub. These modes include point of care (POC) and modular manufacturing (MM).

MHRA defines POC as relating to the “method of manufacture, shelf life, constituents or method or route of administration” which “can only be manufactured at or near the place where the product is to be used or administered.” Modular manufacturing applies to products manufactured or assembled in a self-contained modular unit.

The guidance on GMP for decentralized manufacturing states that applications or variations to an existing license must be submitted for each dosage form. It further notes that “as with any new application or variation, this will be assessed and expected to trigger an inspection based on the principles of Quality Risk Management.”

The guidance addresses how inspections will be conducted for the DM approach. The guidance states that the control site must be in the UK and hold the appropriate MHRA issued manufacturing license.

The control site is the physical site that is mentioned in the clinical trial application and oversees the POC manufacturing system. Other sites are subordinate to the control site.

The guidelines indicate that during an inspection, the following documents should be available at the site:  A control strategy for decentralized manufacturing, a decentralized manufacturing master file (DMMF), clear information regarding the status of each remote site involved in decentralized manufacturing; monitoring processes to ensure data integrity at the site, an initial and ongoing training program, and a qualified person (QP) present at the site.

Guidances: Labelling, UK Guideline on Good Manufacturing Practice (GMP), UK Guideline of Good Pharmacovigilance Practices, Clinical Trial Authorisation (CTA) and Good Clinical Practice (GCP), Marketing Authorisation application, The designation step