Manufacture of IMPs - When is it Reconstitution?

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

Following the Brexit, the UK clinical trials regulations differ from those in the EU Member States. Therefore, the British Medicines and Healthcare products Regulatory Agency (MHRA) published on their blog a post on the manufacture of Investigational Medicinal Products (IMPs). This is relevant for all who wish to conduct clinical trials with investigator sites in the UK or have any IMP manufacturing activities in the UK.

Frequently Asked Questions

The questions and answers are relating to the following topics:

• Manufacture / Reconstitution
• Licensing / Testing
• Stability / Shelf Life
• QPs and Packaging / Labelling Activities

When is it Reconstitution?

According to the blog, the most frequently asked question relates to deciding if an activity should be considered as manufacturing or reconstitution. According to EU GMP Annex 13, the process of reconstitution has to be undertaken as close in time as possible to administration and has to be defined in the clinical trial application dossier and document available at the clinical trial site. The MHRA´s interpretation of "as soon as practicable before administration" is ideally at the bedside, "however it may be acceptable for the activities to be performed in the clinic’s pharmacy e.g. where IMP reconstitution is required to be performed in a clean area such as a laminar air flow cabinet. Preparation of IMP to be subsequently stored for use at a later date would not be considered reconstitution".

Does the IMP release testing need to be carried out in a GMP-certified laboratory?

It would be expected that the analysis would be performed in a GMP-compliant laboratory. However, the certifying QP may rely on the results of analysis from a non-EU laboratory and not repeat testing on import to the EU/UK. In this case, the QPs must assure themselves that the laboratory is compliant with EU GMP as part of the process of supply chain assurance and issuance of the QP Declaration for import.

More information is available in Manufacture of Investigational Medicinal Products – Frequently Asked Questions published on the MHRA Inspectorate´s blog.