Investigational Medicines 2021 UK Guidance

by
MedicinesUK Post-Exit Guidance Notes [2020]
Guidance

Importing Investigational Medicinal Products (IMP) from countries on a list to Great Britain

Updated 20 October 2020

New rules for January 2021

The UK has left the EU, and the transition period after Brexit comes to an end this year.

This page tells you what you’ll need to do from 1 January 2021. It will be updated if anything changes.

For current information, read: Good manufacturing practice and good distribution practice

You can also read about the transition period.

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 ethically approved and authorised by the MHRA. 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 1 January 2021 and there are no changes planned regarding import of IMPs to Great Britain 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 into Great Britain 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 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 QP named on the UK MIA(IMP) 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 from 1 January 2021 to implement this guidance.

IMPs coming to Great Britain from Northern Ireland do not require this additional oversight.

IMPs coming directly to Great Britain 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 Great Britain from a listed country for use in UK clinical trials following QP certification by the listed country MIA(IMP) holder:

  • 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

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

3.2 Documentation available to the QP named on the UK MIA(IMP)

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 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 Great Britain 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 Great Britain clinical trial site

Until the QP named on the UK MIA(IMP)confirms that the batch of IMP has been appropriately certified by the listed country QP, the IMP should not be made available for use by the Great Britain trial sites. 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 Great Britain storage and distribution ‘hub’

You may use a distribution facility to store IMPs imported from a listed country before supply to Great Britain 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 QP named on the UK MIA(IMP). Great Britain 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 Great Britain, but the storage location should be visible to the QP named on the UK MIA(IMP)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 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. Guidance is available on importation of medicines from an approved country for import and the requirements for RPi.

Importation from a country that is not a listed country will require a manufacturers licence.

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

Contact

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. Alternatively, contact your Trade Association by emailing:

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