Documentation relating to compliance with Good Manufacturing Practice (GMP) for Investigational Medicinal Product and Auxiliary Medicinal Product

The manufacturing and import of investigational medicinal products is subject to Good Manufacturing Practice (GMP) requirements or equivalent standards.

Investigational medicinal product

The manufacturing and import of investigational medicinal products is subject to GMP requirements or equivalent standards. The documentation required to show compliance with GMP is outlined in Annex 1, section F of the CTR:

  • for products authorised in the EU (even if not manufactured in the EU) no documentation is required;
  • for products with no EU authorisation, or no authorisation from a country that is a 3rd party to ICH, and not manufactured in the EU, an import authorisation and a QP declaration of GMP equivalence is required. In the latter case, if a Mutual Recognition Agreement (MRA) is in place with the particular country, the latter declaration is not required if the MRA already provides for this equivalence;
  • in  all other cases, an import authorisation is required.

A manufacturaring authorisation is not necessary for the following processes where this process is carried out in hospitals, health centres or clinics for exclusive use in these same places taking part in the same clinical trial in the same Member State (art 61, CTR):

  • the preparation of an investigational medicinal product in a pharmacy in accordance with a medical prescription for an individual patient (commonly known as the magistral formula).
  • the preparation of an investigational medicinal product in a pharmacy in accordance with the prescriptions of a pharmacopoeia and is intended to be supplied directly to the patients served by the pharmacy in question (commonly known as the official formula).
  • the preparation of radiopharmaceuticals used as diagnostic investigational medicinal products.
  • re-labelling or re-packaging by pharmacists or other persons legally authorised in the Member State concerned to carry out such processes.

Auxiliary medicinal products

Auxiliary medicinal products (AxMP) are medicinal products used in the context of a clinical trial as described in the protocol for background treatments, as challenging agents, rescue medication or to assess the end-points. See also the document on auxiliary medicinal products in clinical trials.

In principle, only authorised medicinal products should be used as AxMP in clinical trials (article 59 of the CTR). However, in certain circumstances unauthorised auxiliary medicinal products may be used, for instance an authorised AxMP is not available in the EU or where the sponsor cannot reasonably be expected to use an authorised AxMP. This has to be justified in the protocol.

Where the AxMP is not authorised, or where an authorised AxMP is modified while such modification is not covered by a marketing authorisation, it shall be manufactured according to GMP requirements or to at least an equivalent standard, in order to ensure appropriate quality. The documentation requirements in the application dossier for IMPs also apply to unauthorised AxMPs.