UK Guidance on Decentralised Manufacture for Clinical Trials CTA and GCP

1. Introduction

This guidance provides details on decentralised manufacture (DM) for investigational medicinal products (IMPs) in clinical trials, focusing on clinical trial authorisation (CTA) applications and good clinical practice (GCP) requirements. DM involves partially or wholly decentralised manufacturing processes. https://www.gov.uk/guidance/decentralised-manufacture-clinical-trial-authorisation-cta-and-good-clinical-practice-gcp

2. Definitions and Designation

DM IMPs require a DM designation to confirm justification in the clinical trial context. The CTA must reference this designation and confirm no changes to supporting information. A new designation is needed for significant changes. The designation process is outlined in separate guidance. https://www.gov.uk/guidance/decentralised-manufacture-the-designation-step For trials using both DM and non-DM IMPs, conventional centralised manufacturing applies to non-DM IMPs, such as placebos in most cases.

3. Control Site Requirements

A control site is mandatory for DM IMPs and must be proposed in the CTA application. This site requires certification for DM mode and inclusion of a suitably scoped Manufacturer's/Importer's Authorisation for Investigational Medicinal Products (MIA(IMP)) in the dossier. Submit the DM master file using the provided template. https://assets.publishing.service.gov.uk/media/698db7cf492ea446ea7f42ff/DM_Master_File_Template.docx

4. GCP and IMPD Considerations

General principles of product development, manufacture, and control apply to DM IMPs similarly to conventional IMPs. IMPD requirements follow guidelines on chemical and pharmaceutical quality documentation and quality documentation for biological IMPs. https://www.ema.europa.eu/en/requirements-chemical-pharmaceutical-quality-documentation-concerning-investigational-medicinal-products-clinical-trials-scientific-guideline https://www.ema.europa.eu/en/requirements-quality-documentation-concerning-biological-investigational-medicinal-products-clinical-trials-scientific-guideline Include batch analysis data from a representative number of DM locations in IMPD section P.5.4 to ensure quality compliance. Process validation or extended characterisation may be required for comparability, especially for complex products.

5. Real-Time Release Testing (RTRT)

For RTRT, demonstrate enhanced product and process knowledge in IMPD section P.2. Include representative process validation for multiple batches at critical steps in section P.3.5. The RTRT strategy must be based on understanding manufacturing processes, parameters, controls, and IMP attributes. Refer to guidelines on real-time release testing and Eudralex Volume 4 Annex 17. https://www.ema.europa.eu/en/real-time-release-testing-scientific-guideline https://health.ec.europa.eu/document/download/78d31fc9-760f-4fe9-9ccd-95595ef48a71_en?filename=2018_annex17_en.pdf

6. Blinding in Trials

Maintain blinding to avoid bias in safety and efficacy assessments. The sponsor is responsible for protocol measures to protect blind integrity, with formal assessments during setup and periodic reviews. For point-of-care manufacture, ensure manufacturing and administration do not reveal treatment assignment through process, time, appearance, characteristics, or record keeping. Additional information on labelling is available. https://www.gov.uk/guidance/decentralised-manufacture-labelling

7. Compliance with GMP and GCP

Compliance is ensured through batch analysis, process validation, and comparability demonstrations across DM locations.