illev Pharma East has a highly educated and dedicated team of international experts with many years of experience in Pharmaceutical industry.

3 March 2022

Investigational medicinal products (IMPs)

EMA Guidelines on the requirements for quality documentation concerning medicinal products in clinical trials 

European Medicines Agency published on their website final Guidelines (Revision 2) on the quality requirements for investigational medicinal products (IMPs);

Addresses the documentation on the chemical and pharmaceutical quality of IMPs and Auxiliary Medicinal Products containing chemically defined drug substances, synthetic peptides, synthetic oligonucleotides, herbal substances, herbal preparations and chemically defined radio-active/radio-labelled substances to be submitted to the competent authority for approval prior to beginning a clinical trial in humans. It includes the requirements for IMPs and Auxiliary Medicinal Products to be tested in phase I, phase II, phase III and phase IV studies as well as the requirements for modified and unmodified comparator products and IMPs to be tested in generic bioequivalence studies.

Addresses the specific documentation requirements on the biological, chemical and pharmaceutical quality of IMPs containing biological/biotechnology derived substances. It also lists, as regards documentation on the biological, chemical and pharmaceutical quality of the IMP, examples of modifications which are typically considered as ‘substantial’. Advanced Therapy Medicinal Products are excluded from this guideline.


The date of coming into effect was 31 January 2022, which is also the application date of the Regulation (EU) No. 536/2014 on clinical trials (CTR).

New Guidelines will be of great help to sponsors of IMPs for new drugs and biologics while deciding whether manufacturing changes are considered a “substantial modification” needing prior approval. Both Guidelines namely replace an earlier version issued in 2017 (2018 for biological IMP’s) by including a new section on the changes to the investigational products which need prior approval or “substantial modification” applications before restarting clinical trials.

In general, all IMPs should be produced in accordance with the principles and the detailed guidelines on Good Manufacturing Practices (GMP) for IMPs (EU GMP Annex 13, Detailed Commission guidelines on good manufacturing practice for investigational medicinal products for human use, pursuant to the second subparagraph of Article 63(1) of Regulation (EU) No 536/2014).

Here at Billev Pharma East, we have been helping organisations for over 10 years to achieve quality and operational excellence. We have experience implementing and consulting with organisations of all sizes, therefore, we can offer an expert perspective on successfully implementing a new legislation, regulation requirements into your organisation quality management system.