12-14 December 2023
The final EMA Guidelines (Rev. 2) on the quality requirements for pharmaceutical and biological investigational medicinal products (IMPs) have been released on the EMA website together with an overview of comments received on the draft guidelines published last year. 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).
According to the agency, it should be clearly differentiated between the requirements for an Investigational Medicinal Product Dossier (IMPD) for a clinical trial (CT) and a marketing authorization dossier. Information to be provided for IMPs should focus on the risk aspects and should consider the nature of the product, the state of development / clinical phase, patient population, nature and severity of the illness as well as type and duration of the CT.
The guideline provides the documentation requirements on the chemical and pharmaceutical quality of IMPs and Auxiliary Medicinal Products (AxMPs) containing
Requirements for IMPs and AxMPs to be tested in phase I - IV studies as well as the requirements for comparators and IMPs to be tested in generic bioequivalence studies are included. Guidance on standard information which should usually be presented in the quality part of an IMPD is provided (for certain situations, e.g. where the DS from the specific source to be used for an IMP is already included in a medicinal product authorized within the EU a simplified IMPD will suffice). In addition, examples are provided for changes to IMPs, containing chemically defined or herbal DS, and their classification (e.g., Substantial Modification (SM), Non-substantial Modification (NSM)).
The guideline addresses the specific documentation requirements on the biological, chemical and pharmaceutical quality of IMPs containing biological / biotechnology derived substances and applies to proteins & polypeptides (produced from recombinant or non-recombinant cell-culture expression systems), their derivatives, and products of which they are components (e.g. conjugates). Moreover, the guideline lists examples of modifications which are typically considered as "substantial". The guideline also applies to AxMPs containing proteins & polypeptides as active substances. The principles may also apply to other product types such as proteins & polypeptides isolated from tissues and body fluids. However, Advanced Therapy Medicinal Products (ATMPs) are out of scope.
Many of the comments received related to the question "What is a SM / NSM?". Some of the comments addressed, for example, the following topics:
For further information please see the two EMA guidelines (Rev. 2) on the requirements to the chemical and pharmaceutical quality documentation concerning IMPs and on the requirements for quality documentation concerning biological IMPs.