Marlene Kim is a Chemist at FDA Office of the Commissioner/Office of Digital Transformation/Office of Data, Analytics, and Research/Health Informatics Staff.

Marlene Kim

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Drug Master File (DMF) holders provide a hazard assessment for impurity classification to comply with International Council for Harmonisation (ICH) M7 (R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (1) that includes the use of (quantitative) structure-activity relationship ((Q)SAR) models. Impurities 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 application of (Q)SAR models and registration in the FDA Global Substance Registration System (GSRS)—or for use in the Chemistry, Manufacturing, and Controls (CMC) review document, requires conversion of the structures to a computer-readable format. To resolve challenges with re-drawing chemical structures and to improve review efficiency, inclusion of structural information in the structure-data file (SD File) format can be very helpful in DMF reviews.

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Barbara Scott* is a Master Reviewer at FDA Center for Drug Evaluation and Research/Office of Pharmaceutical Quality/Office of New Drug Products/ Division of Lifecycle Active Pharmaceutical Ingredients, Barbara.Scott@fda.hhs.gov. David Green is a Senior Pharmaceutical Quality Assessor at FDA Center for Drug Evaluation and Research/Office of
Pharmaceutical Quality/Office of New Drug Products/ Division of Lifecycle Active Pharmaceutical Ingredients. Marlene Kim is a Chemist at FDA Office of the Commissioner/Office of Digital Transformation/Office of Data, Analytics, and Research/Health Informatics Staff. Naomi Kruhlak is Scientific Lead, Computational Toxicology Consultation Service at FDA Center for Drug Evaluation and Research/Office of Translational Sciences/Office of Clinical Pharmacology/ Division of Applied Regulatory Science. Tyler Peryea is a Chemist at FDA Office of the Commissioner/Office of Digital Transformation/Office of Data, Analytics, and Research/Health Informatics Staff. David Skanchy was the Division Director (retired) at FDA Center for Drug Evaluation and Research/Office of Pharmaceutical Quality/Office of New Drug Products/ Division of Lifecycle Active Pharmaceutical Ingredients.

*To whom all correspondence should be addressed.

Pharmaceutical Technology/Pharmaceutical Technology Europe

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When referring to this article, please cite it as Scott, B. et al. Master File Submission of Structures. 

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The SD File format offers benefits for KASA and cheminformatics to support regulatory submissions.