The application to carry out a clinical trial (Investigational Medicinal Product Dossier, IMPD) is a document which must contain all the relevant quality information regarding the manufacture, testing and packaging of APIs as well as of investigational medicinal products. The chapter structure of the IMPD is comparable to the format of the CTD: sections S are dedicated to information about the API (from S.1. = General Information to S.7. = Stability). Sections P include information about the investigational medicinal product under test (from P.1. = Description and composition of the investigational medicinal product to P.8. = Stability).
A set of requirements for chemical investigational products regarding the detailed content of the IMPD was established in 2006. A draft for consultation for biological and biotechnological investigational medicinal products was published at the end of 2010. Now - almost 9 months after the expiry of the consultation deadline - the European Medicines Agency has published the final guideline entitled: "Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials".
The new guidance document applies to proteins, polypeptides, their derivatives, and conjugates.
Beside requirements on documentation regarding the manufacture, testing and packaging of APIs and investigational medicinal products (which are already known from the "chemical" guideline), the new document also describes which elements must be documented by the applicant regarding biotechnological properties.
The chapter about "Control of critical steps and intermediates" (P.3.4.) contains - among other things - detailed information about the required documentation for sterilisation by filtration. In the chapter "Excipients of human or animal origin", information can be found about viral safety documentation. More details are contained in appendices "A.2. Adventitious agents safety evaluation" concerning microbiological contamination.
Major changes in the manufacture, testing and packaging must be reported and documented. Chapter 4 "Substantial Amendments" presents a list of 9 elements which are considered as substantial changes - according to the guideline - like the extension of the shelf-life for example. In the context of a clinical trial, it may be useful to extend the shelf-life of the investigational medicinal product. However, the applicant has to undertake the corresponding stability studies in accordance with the approved stability protocol. Shelf-life extension that goes beyond twice the accepted duration or extension up to 12 further months is not considered as a substantial change. Shelf-life extension that goes beyond the accepted extension or missing stability protocol for this extension are - in turn - a substantial amendment which must be justified and documented.
Please also see the complete "Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials".
Note: At the conference "How to write the Quality Part of an IMPD" on 13/14 November 2012 in Vienna, Austria, you will get first-hand information from a member of the EMA's working group (BWP) who has worked on the elaboration of this Guideline.
Dr Gerhard Becker
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)