Efficient Creation of CMC Submission Documents

There is ample room for improving efficiency in the creation of CMC documents for submissions, and this need is magnified for the preparation of eCTD documents. This article will introduce the current challenges and suggest solutions for improving efficiencies, according to the following topics that will be addressed in separate articles in this blog:

1. CMC eCTD Challenges and Solutions
2. The CMC Submission Team – see separate article
3. Mapping and Planning – see separate article
4. Granularity and Life Cycle Management – see separate article
5. Annotated Templates – see separate article
6. Submission-Ready Documents – see separate article
7. The Module 2 Quality Overall Summary and Key Messages– article to be written
8. Document Management – article to be written

Note: Chemistry, Manufacturing, and Controls (CMC) Documents are written for various applications:

• Clinical Applications:
– IND – Investigational New Drug Application
– CTA – Clinical Trial Application (EU)
– IMPD – Investigational Medicinal Product Dossier (EU)
• Marketing Applications:
– NDA – New Drug Application
– BLA – Biologics License Application
– ANDA – Abbreviated New Drug Application
– MAA – Marketing Authorization Application
• Drug Master Files (DMF)
• Amendments, Responses to agency questions
• Post-Approval Supplements and Variations, Annual Reports

CMC eCTD Challenges and Solutions

Writing CMC documents in eCTD has created more challenges than in other areas of the eCTD. With eCTD submissions, ownership is pushed back to the functional areas who create the pdf documents. Authors who have traditionally written their documents using their technical expertise, have to shift to a new era where publishing standards must be taken into account. Authors not only must understand the regulatory guidance and regional differences, but also must be trained on the use of eCTD templates for an efficient publishing process. Many of these technical folks have not needed to be proficient in Microsoft Word, but now they are being asked to create hyperlinks and stick to the style guide.

Take this new challenge and multiply it by the number of authors that contribute to Module 3. The authors come from various functional areas and contract manufacturing organizations. There must be effective leadership of the CMC submission group to coordinate consistent messages, terminology, format, and content in the various sections of Module 3.

If that’s not enough challenge in an organization transitioning to eCTD, the CMC authors must also understand the concept of life cycle management in order to decide on the appropriate granularity of the documents in Module 3. In addition, the reviewability of the eCTD document is dependent on the accuracy and effectiveness of the hyperlinks and bookmarks.

From interviews with eCTD vendors and industry sponsors alike, Module 3 has been the greatest challenge in the transition to eCTD.

The key problem is:
The publishing group doesn’t understand the CMC content to make decisions about granularity, hyperlinks, and bookmarks.
The CMC group has not historically understood the publishing process to know why this information is important to publishing, and the publishing process has also been evolving with the eCTD transition.

The key solution is:
The publishing group, Regulatory Affairs, and the CMC group must work as a team to create eCTD documents as efficiently as possible.
Suggested processes such as CTD mapping, annotation of templates, and preparation of submission-ready documents (described below) will improve efficiency if the team supports the processes.

See separate articles on:
• The CMC Submission Team
• Mapping and Planning
• Granularity and Life Cycle Management - to be updated in the future with case studies
• Annotated Templates
• Submission-Ready Documents
• The Module 2 Quality Overall Summary and Key Messages
• Document Management