The QP Oversight Process

The MHRA introduced the QP Oversight process for clinical supplies entering into Great Britain from the EU/EEA after Brexit. The Medicines for Human Use (Clinical Trial) Regulations 2004 requires that all interventional clinical trials to be ethically approved and authorised by the MHRA.  For IMPs that are imported from “an approved list” that have been certified by a QP in a listed country EU/EEA a system is required to assure that the initial QP certification has occurred. The assurance system must be overseen by a QP (the QP Oversight process) and is performed by a QP named on a UK MIA(IMP).

IMPs may be either:

• sent direct to the Great Britain clinical trial site

• via a Great Britain storage and distribution ‘hub’

Both require the oversight of a UK MIA(IMP) holder and QP, with systems in place to ensure that:

• IMPs are not made available for use in Great Britain clinical trial sites until appropriate QP certification in a listed country has been verified by the QP named on the UK MIA(IMP)

• IMPs are only shipped to appropriate Great Britain trial sites detailed within the UK trial application

• up-to-date information and documentation relating to the clinical trial and associated Product Specification File are made available by the Sponsor to the QP named on the UK MIA(IMP)

• the clinical trial is authorised by the MHRA before IMP is made available to the Investigator

There should be written agreements which describe the assigned responsibilities and provision of relevant information between the organisations. These include agreements between:

• sponsor and the UK MIA(IMP) holder responsible for the oversight of import from the listed country

• sponsor and the listed country MIA(IMP) holder

• UK MIA(IMP) holder and Great Britain storage and distribution hub (if applicable)

• sponsor and Great Britain storage and distribution hub (if applicable)

The QP named on the UK MIA(IMP)should have the following documentation available as part of the oversight process for import of IMP to Great Britain from listed countries:

• details of the manufacturing and distribution supply chain.

• the UK Clinical Trial Application form, plus amendments. This should be used to confirm the site responsible for final certification of the finished IMP.

• the UK Clinical Trial Application and any amendment approval records (including any post approval commitment requirements).

• evidence that the certifying site in the listed country is appropriately licensed and holds a current GMP certificate for the IMP dosage form(s) and associated activities (e.g. manufacture, packaging, testing and / or import from a third country).

• details of the approved Great Britain trial sites from the ethics application, plus any updates or amendments.

• details of each shipment of IMP to Great Britain including the addressees’ information. This should be verified against the ethics approvals.

• details of any excursions from the stated storage conditions during shipment, along with any decisions taken by the Sponsor and certifying QP, and the rationale for those decisions.

• details of the responsibilities described in the written agreement between the Sponsor and the listed country MIA(IMP) holder.

This is not an exclusive or exhaustive list as requirements may vary depending on the responsibilities of each organisation in the supply chain.

Evidence of initial QP certification can be confirmed via the following:

• Batch certificate confirming QP certification in accordance with Article 13.3 of Directive 2001/20/EC

• Statement of certification (ad-hoc, confirming certification in accordance with Article 13.3 of Directive 2001/20/EC)

• Access to the certifying MIA(IMP) holder’s internal systems (e.g. global Enterprise Resource Planning system) that confirms batch certification

If you import authorised or unauthorised products for use in a UK clinical trial in Great Britain that are:

• non-investigational medicinal products

• unmodified comparators to be labelled in Great Britain prior to QP certification and release to the clinical trial,

importation from a listed country should use a wholesale dealer’s licence (WDA(H)). A Responsible Person for import (RPi) may be required.

Obtaining non-investigational medicinal products from Northern Ireland will require a WDA(H), unless you are the Sponsor of the clinical trial.

The decision whether to perform direct shipments to clinical sites or to use a hub is something that needs to be considered by the Sponsor as there are justifications for each option.

Direct shipments can provide a just in time approach that does not have supplies siting in the UK that could be used at other trial sites, however, the provision of import licences and customs clearance issues and temperature excursions may lead to delay in the supplies reaching the clinical site in the timeline required for dosing. The QP oversight process will also need to be completed once the supplies are within the UK adding additional time to the process. Each individual shipment will require the QP oversight to be performed, where there are multiple sites with multiple shipments the cost savings of using a UK hub may not be as great as first perceived.

Direct shipments or the use of a UK hub is something that a Sponsor needs to consider on a “case by case” basis for each study.