Good Manufacturing Practice for Investigational Medicinal Products and Auxiliary Medicinal Products

The authorisation requirement applies to all steps in the manufacturing process: drug product manufacturing, packaging/re-packaging, labelling/re-labelling/blinding, import to EU/EES if applicable and release within EU/EEA. Release shall be performed by a Qualified Person (QP). The same rules apply for unauthorised Auxiliary Medicinal Products (AxMP).

In order to obtain a Manufacturer/Importer Authorisation (MIA), the IMP should be manufactured by applying Good Manufacturing Practice (GMP) according to Regulation (EU) 2017/1569. The Commission has published Guidelines in line with the Regulation. The Regulation and Guidelines also refer to chapters and annexes in EU-GMP (Eudralex Volume 4).

Verification of GMP compliance in the clinical trial application – drug product manufacturing

All manufacturers included in the drug product manufacturing process for unauthorised IMPs and AxMPs, should be presented in the clinical trial application, normally as part of the pharmaceutical quality documentation (Investigational Medicinal Product Dossier – IMPD).

The following documents should be provided in the clinical trial application to verify compliance with EU-GMP for all manufacturers.

Manufacture in Sweden:

• a copy of a valid MIA, GMP-certificate or a reference to the authorisation number.

Manufacture in other EU/EEA countries:

• a copy of a valid MIA or GMP-certificate, translated to English or Swedish if applicable.

Manufacture in a country outside of EU/EEA, which has a Mutual Recognition Agreement (MRA) with EU:

• a QP-declaration or a copy of a valid MIA or GMP-certificate from the issuing authority in the particular country
  
  • The QP responsible for import of the IMP into EU/EES, verifies in the QP-declaration that the manufacturing outside of EU/EEA is performed in line with EU-GMP or comparable standards. The declaration should include the basis for the QP’s assessment, generally an on-site audit.
  • MRAs are bilateral agreements between EU and each country. It should be noted that each MRA has a different scope, meaning that IMP manufacturing is not included in all MRAs. If a MRA that covers IMP is in place with the particular country, QP-declaration is not required, only MIA or GMP-certificate.
• a copy of a valid MIA or GMP-certificate for manufacturers responsible for import and QP-certification within the EU/EEA.

Manufacture in a country outside of EU/EEA, which does not have a MRA with EU:

• a QP-declaration (more information on QP-declarations above)
• a copy of a valid MIA or GMP-certificate for manufacturers responsible for import and QP-certification within the EU/EEA.

A QP-declaration template is available in EudraLex Volume 10, Clinical trials guidelines, Chapter III:

Verification of GMP compliance in the clinical trial application – drug substance manufacturing

For chemically manufactured active substances, compliance with EU GMP Part II, section 19 is recommended, but not required. GMP-verification documents are not required in the application.
For biotechnologically manufactured substances and Advanced Therapy Medicinal Products (ATMP), compliance with EU GMP Part II (annex 2) and Part IV, is generally required. GMP verification as described above for manufacturing of IMPs should be provided in the CTA.