Guidance

Importing Investigational Medicinal Products (IMP) from EEA to UK

Updated 10 October 2019

This guidance was withdrawn on 24 February 2020

For current information on Importing investigational medicinal products from approved countries see Good manufacturing practice and good distribution practice

1. Introduction

The requirements and procedures for clinical trials in the UK are set out in the Medicines for Human Use (Clinical Trials) Regulations 2004. These regulations require all interventional clinical trials to be authorised by the MHRA and ethically approved. They also include requirements for the application and assessment of each trial, the supply of investigational medicinal products (IMPs), the conduct of clinical trials in accordance with Good Clinical Practice and safety reporting.

Detailed guidance on the manufacture and import of IMPs are described in Eudralex Volume 4 and Eudralex Volume 10, including guidance for the issuance of the Qualified Person Declaration for the importation of IMPs manufactured in third countries outside the EEA. These requirements will remain in effect following the UK’s exit from the EU and there are no changes planned regarding import of IMPs to the UK from countries outside of the EEA.

2. Import of IMPs from an approved country

If you are the Sponsor of a UK clinical trial using IMPs imported from countries on an ‘approved country for import’ list (initially, all EU and EEA countries) you will require a UK Manufacturing and Import Authorisation (MIA(IMP)) holder to put in place an assurance system to check these IMPs have been certified by a Qualified Person (QP) in a listed country, before release to the trial.

This assurance system must be overseen by a UK QP, however the IMPs would not require recertification. The routine tasks relating to verification of QP certification in a listed country may be delegated by the UK QP to appropriate personnel operating within their MIA(IMP) quality system.

A Sponsor may perform verification of QP certification in a listed country themselves if they are the holder of a UK MIA(IMP). Alternatively, they may outsource this verification to a third party who holds a UK MIA(IMP).

There will be a one-year transition period following the date of the UK’s exit from the EU to implement this guidance.

IMPs coming directly to the UK from third countries that are not on the approved country for import list will continue to require import and QP certification in the UK by the MIA(IMP) holder as per the existing requirements.

3. Oversight process

There are two routes for IMPs to be received into the UK from a listed country for use in UK clinical trials following QP certification by the listed country MIA(IMP) holder:

• direct to the clinical trial site
• via a UK 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 the trial until appropriate QP certification in a listed country has been verified by the UK QP
• IMPs are only shipped to appropriate trial sites detailed within the UK trial / ethics application
• Up-to-date information and documentation relating to the clinical trial and associated Product Specification File are made available to the UK QP by the Sponsor
• In addition to QP certification in the listed country, the clinical trial is authorised by the MHRA before IMP is made available to the Investigator

3.1 Written agreements

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 UK storage and distribution hub (if applicable)
• Sponsor and UK storage and distribution hub (if applicable)

3.2 Documentation available to the UK QP

The UK QP should have the following documentation available as part of the oversight process for import of IMP to the UK 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 UK trial sites from the ethics application, plus any updates or amendments.
• Details of each shipment of IMP to the UK 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 because information requirements may vary depending on the responsibilities of each organisation in the supply chain.

3.3 Acceptable evidence of QP certification

Written evidence should be available to demonstrate that each batch of IMP imported from a listed country has been QP certified for use in the specified UK trial. This should be verified prior to the first shipment of IMP from each batch to the UK trial site(s).

Not all options listed below may be suitable for different supply chain relationships, however just one of these pieces of evidence is sufficient to satisfy the requirements of the Regulations. Other evidence may be acceptable provided it confirms that QP certification has taken place for the batch in question.

Batch certification by a Qualified Person may be confirmed using evidence such as:

• 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

4. Supply of IMP to a clinical trial site

Until the UK QP confirms that the batch of IMP has been appropriately certified by the listed country QP, the IMP should not be made available for use in the trial. This is in addition to the two-step release procedure described in EU GMP Annex 13. Regulatory release of the IMP may be given for some countries at different times therefore the Sponsor should ensure the regulatory release is in place for the UK prior to IMP being made available for use in the trial.

5. Using a UK storage and distribution ‘hub’

You may use a distribution facility to store IMPs imported from a listed country before supply to UK clinical trial sites. IMPs may be imported to the distribution hub from a listed country before confirming that QP certification has taken place in the listed country if they are segregated electronically or physically until certification has been confirmed by the UK QP. UK storage and distribution facilities should be named on the UK MIA(IMP) of the company responsible for oversight of the import.

6. Reference and retention samples

Additional reference and retention samples are not specifically required to be stored within the UK, but the storage location should be visible to the UK QP and defined in the written agreement with the Sponsor. Provision for timely access to the samples by the UK competent authority should be made within the relevant written agreements.

7. Importing non-investigational medicinal products for use in a clinical trial

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

• non-investigational medicinal products
• unmodified comparators to be labelled in the UK prior to QP certification and release to the clinical trial

This should be imported from a listed country using a wholesale dealer’s licence (WDA(H)).

A Responsible Person for import may be required. Guidance is available on importation of medicines from an approved country for import and the requirements for Responsible Person for import.