In the previous two articles, we have shared our experience on various aspects of effective IND/IMPD CMC writing, considering proper planning, assigning a dedicated CMC writing team, and having effective project management. In addition, we discussed technical writing particulars giving some key messages on document preparation. Now, we will discuss other important points. These are safety, data completeness, and geographical regions.
Safety first
The IND/IMPD is a regulatory document submitted to the Competent Authorities for an investigational medicinal product to receive approval to initiate clinical investigations in humans. In this respect, the CMC data are the first data submitted to the Competent Authorities representing the quality of the investigational product. In this role, with support from toxicological studies, CMC data play a key role in providing evidence that the investigational product is safe for humans’ administration and demonstrate Sponsor readiness to embark on the clinical research journey. Here, the safety of the investigational product goes first, along with the efficacy and other characteristics as intended.
From the CMC regulatory point of view, we should admit that CMC data at this stage of development is limited in terms of manufacturing process verification, development of analytical control methods, and availability of stability data. Therefore, the correct and proficient presentation of CMC data in the IND/IMPD is very important, according to which the investigational product is assessed in terms of expected purity, potency, and safety.
Concept of Completeness
When planning a clinical trial and IND/IMPD submission timelines, the Sponsor should carefully consider the progress of the CMC development, closely monitoring it with the CMC development team, learning when the required CMC data are ready. Very often, the dilemma is whether to submit fewer data earlier and then supplement the file at later stages of clinical development or to prepare a more detailed submission file that will take a little longer and delay IND/IMPD submission.
A commonly utilized approach for CMC submission is a file building approach, where the submission proceeds fulfilling minimum requirements at the time of submission and is then complemented at the later stages as clinical trials progress. Although there is no single answer and it depends on the situation, a minimal approach with a minimum required CMC information is very often used for early clinical trials.
Therefore, although clinical operations want to start clinical investigations earlier, there is the CMC regulatory to determine the minimum requirements for the submission of IND/IMPD and whether they are ready. Certainly, the situation may vary depending on the type of a product, if it is a novel compound or any modification of an already authorized medicinal product where information on drug substance is already available to the Competent Authorities.
Regions
In regard to the IMPD, very often a question comes up whether to develop the document as a single file for all countries or adapt it to specific regions or markets if the Sponsor is planning multi-regional, multi-country clinical trials.
In response, I would say that generally a single CMC document is prepared for the submission of the IMPD in different markets and is adapted at the request of the Competent Authorities, as required, unless very specific requirements are set in the country, that require a separate preparation of CMC part.
In this regard, it is advisable to work closely with the product development project team to learn about the situation if additional countries are added or commercial priorities change, and that clinical operations change their plans or priorities accordingly.
If you want to obtain more information on effective IND/IMPD writing, contact us!
Ramune Rukiene, MSc
Director Regulatory Affairs
Biomapas
