How to release IMPs in the EU

The manufacturing of Investigational Medicinal Products (IMPs) or Clinical Trial Material (CTM) is more complex than the manufacturing of marketed products. The same is applicable for the role of the Qualified Person (QP). But also manufacturers outside the EU who want to run clinical trials in the EU need to consider a few things:

The role of the Qualified Person (QP)

The QP is responsible for certifying that each batch of investigational medicinal product has been produced and tested / checked in accordance with

• EU GMP
• The Product Specification File
• The IMPD (Investigational Medicinal Product Dossier) or the CTA (Clinical Trial Authorisation)
• The Product Specification File (according Annex 13 to the EU-GMP Guide)

The IMP QP is accountable from manufacture all the way to the patient by

• assessing GMP issues
• participating in inspections and audits at sites involved in the manufacturing and distribution of IMPs
• being a reliable contact for the health authorities
• knowing applicable legislation and processes including exceptions which may impact the quality and safety of the IMP
• being involved in complaint handling and recall processes

Release or certification?

The terms QP release and QP certification, are often (incorrectly) used interchangeably. However the responsibilities for release and certification are defined in clinical trials legislation. In EU-GMP Annex 13, the term "Certification by the QP" is used.

Two-step release procedure

Release of IMPs for use in a clinical trial should not occur until after the QP has certified the batch. The sponsor may not start a clinical trial until the clinical trial authorisation has been granted for the trial and all conditions of the authorisation have been met; and an Ethics Committee positive opinion has been granted and each trial site has been approved (Article 9 of 2001/20/EC).

Although the QP certification and regulatory approval processes may be run in parallel, the sponsor is responsible for ensuring both steps are completed prior to the release of IMPs for use in a clinical trial. (source: MHRA FAQs)

Product Specification File (PSF)

The PSF is a reference file containing, or referring to files containing all the quality information related to an IMP. The content can vary depending on the product and stage of development. It should be accessible by the QP as a basis for QP certification. Where different manufacturing steps are carried out at different locations, separate files may be maintained at these locations.

Import into EU

An IMP can only be imported by a pharmaceutical manufacturer with a respective import license and a Qualified Person.