Updated – Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials
A guideline has been published by the European Medicines Agency regarding clinical trials on medicinal products for human use.
This guideline is linked to Regulation (EU) No. 536/2014 and repealing Directive 2001/20/EC. This guideline outlines the documentation requirements on the biological, chemical, and pharmaceutical quality of investigational medicinal products (IMPs) containing biological and biotechnology derived substances. The guidance applies to proteins and polypeptides, which are created from recombinant or non-recombinant cell-culture expression systems and Auxiliary Medicinal Products that contain these proteins and peptides. The guideline states that information regarding the nomenclature of the active substance should be given, along with a description of the structure and the general properties of the active substance. The names and addresses of each manufacturer should also be provided.
Additionally, a flow chart outlining the process parameters and in-processing testing should be provided. Reprocessing should be justified and described. In regards to the control of materials, materials used in the manufacturing of the active substance should be listed and describe where each material was used in the process.
Raw materials of animal or human origin, both the source and stage of the manufacturing process in which the material was utilized should be indicated. Safety information should be listed in Appendix A.2. Tests and acceptance criteria for the control of critical steps in the manufacturing process should also be provided. Any changes made to the manufacturing process should be summarized and allow for clear identification, and may require a comparability exercise to ensure that the change does not cause adverse effects. The guideline also states that process and product related impurities should be addressed, including the maximum amount for the highest clinical dose. Defined acceptance criteria and testing of the active substance is required for quantity, identity and purity.
For analytical procedures, the guidelines states that analytical methods for tests should be reported and suitability of the methods should be confirmed due to its evolving nature. Packaging material information of the active substance should also be provided, including any possible interactions between the active substance and the packaging. The stability protocol for the storage of the active substance should also be provided, including information on the specification, analytical methods and test intervals.
Active substances should be kept in a container closure system and be made of the same materials in the batch storage for the clinical trials. The shelf-life of the active substance’s storage should be indicated and include an evaluation of available data. Maximum shelf-life should not exceed more than twelve months longer that the time covered by real time stability data.
