Last month, we reviewed some of our Research Collaboration Agreement (RCA) activities with the US Food and Drug Administration (FDA).1 This included a joint project to develop an internal FDA/CDER system (based on the Leadscope technology) to enter, validate, and register chemicals linked to internal (Q)SAR consultation reports. This information, along with access to toxicity databases, is made available internally to FDA/CDER reviewers through a simple web-based user interface. As part of the current FDA/CDER workflow, chemical structures are manually re-drawn from the PDF submissions before being validated, registered, and stored in the database.

The US FDA has recently made several presentations describing the benefits of avoiding this manual re-drawing of chemical structures by requesting Drug Master File (DMF) Holders to submit an electronic record of these chemicals.2,3 Such chemicals would include starting materials, impurities, intermediates, by-products, and degradants. Having access to an electronic representation of the chemical structures would avoid the time-consuming process of isolating and re-drawing the chemicals, which is also prone to errors. This in turn enables a more efficient use of resources.

It is now possible to submit structures in a computer-readable format, as an SD file, since it has been added as an acceptable file format as part of the Electronic Common Technical Document (eCTD)5. The SD file format is a commonly used electronic representation of a chemical structure and associated tabular data.4 This information has recently been posted on the FDA’s website.5

For DMF Holders to implement a process, a trusted technology is needed for collecting, formatting, annotating, and validating their SD files for submission. To address this need, we have developed a solution for creating such SD files, including structure drawing and rigorous structure validation.

If you would like to discuss this in more detailed, please contact me (Glenn Myatt; glenn.myatt@instem.com).

Reference

  1. In silico insider blog: US FDA collaborations – predicting mutagenicity and beyond…
  2. US FDA poster: Structure-Data File from Sponsors’ Submissions Promotes Rapid Chemical Registration and Computational analyses –
  3. US FDA poster: Stop Re-drawing Chemicals! Implementation of Computer-Readable Chemical Structure Format for Drug Impurities –
  4. Quick Guide to Creating a Structure-Data File (SD File) for DMF Submissions
  5. Drug Master File (DMF) Submission Resources

Published by Glenn Myatt

Glenn J. Myatt is the co-founder of Leadscope and currently Senior Vice President, In Silico & Translational Science Solutions at Instem with over 25 years’ experience in computational chemistry/toxicology. He holds a Bachelor of Science degree in Computing, a Master of Science degree in Artificial Intelligence and a Ph.D. in Chemoinformatics. He has published 34 papers, 10 book chapters and three books.