Issue link: https://www.e-digitaleditions.com/i/1514991
6 Pharmaceutical Technology ® Regulating Innovation, Quality, and Risk eBook January 2024 PharmTech.com AREE - stock.adobe.com D rug Master File (DMF) holders provide a hazard assessment for impurity classifica- tion to comply with International Council for Harmonisation (ICH) M7 (R2) Assess- ment and Control of DNA Reactive (Mutagenic) Impu- rities in Pharmaceuticals to Limit Potential Carcino- genic Risk (1) that includes the use of (quantitative) structure-activity relationship ((Q)SAR) models. Im- purities consist of starting materials, intermediates, by-products, and degradants and can total >15 for a single DMF. Currently, chemical structures for these impurities are submitted in the Electronic Common Technical Document (eCTD) (2) as unmanipulable portable data files (PDF files). Further review of the impurities using cheminformatics tools—by appli- cation of (Q)SAR models and registration in the FDA Global Substance Registration System (GSRS)—or for use in the Chemistry, Manufacturing, and Con- trols (CMC) review document, requires conversion of the structures to a computer-readable format. To resolve challenges with re-drawing chemical struc- tures and to improve review efficiency, inclusion of structural information in the structure-data file (SD File) format can be very helpful in DMF reviews. In 2021, the Division of Lifecycle Active Pharma- ceutical Ingredients (DLAPI) in FDA's Center for Drug Evaluation and Research (FDA/CDER), Office of New Drug Products (ONDP) began offering DMF holders the option to provide impurity structures as a sin- gle SD File. The agency also compiled a Quick Guide to assist industry in SD File creation (3). The SD File provides an extensible, portable text file encoding computer-readable chemical structures linked to as- sociated data fields. Under a collaboration between FDA/CDER's Office of Pharmaceutical Quality (OPQ), Office of Translational Science (OTS) and FDA's Of- f ice of t he Com m issioner (OC), DMF holders may now provide SD Files as part of the eCTD through Master File Submission of Structures Barbara Scott, David Green, Marlene Kim, Naomi Kruhlak, Tyler Peryea, and David Skanchy The SD File format offers benefits for KASA and cheminformatics to support regulatory submissions.