Comparative Review of Drug Master File Regulation in the US, Brazil and Malaysia

Abstract

The Drug Master File (DMF) is an important regulatory document that contains confidential information related to the manufacturing, processing, packaging, storage, and quality control of pharmaceutical products and active pharmaceutical ingredients (APIs). It supports regulatory submissions such as INDs, NDAs, ANDAs, and marketing authorization applications while protecting proprietary information. This review provides a comparative study of DMF regulations in the United States, Brazil, and Malaysia. In the United States, the FDA regulates DMFs under 21 CFR 314.420 with mandatory electronic submissions in eCTD format. Brazil follows the DIFA and CADIFA framework regulated by ANVISA under RDC 359/2020, focusing on API quality and CTD-based submissions. Malaysia, regulated by NPRA, follows ASEAN Common Technical Dossier (ACTD) guidelines and accepts DMF, CEP, and ACTD Part II-S submissions. The review compares regulatory requirements, submission procedures, documentation review timelines, lifecycle management, and electronic submission systems among these countries. It also highlights the increasing adoption of harmonized electronic submission formats and the importance of DMFs in achieving global pharmaceutical regulatory compliance and market authorization. A comparative chart developed in this study effectively illustrates these differences and similarities, serving as a valuable resource for pharmaceutical companies navigating the complexities of international drug approval. Ongoing dialogue and collaboration among regulatory authorities are essential for harmonizing DMF requirements, which will streamline processes and enhance global competitiveness. Understanding the DMF regulatory framework across these regions is crucial for manufacturers to manage submissions and maintain compliance while protecting proprietary information efficiently. Furthermore, advancements in electronic submission methods, such as the eCTD format, are set to enhance regulatory efficiency, ensuring the timely delivery of safe and effective pharmaceutical products to the market. This review ultimately underscores the critical role of DMFs in the pharmaceutical regulatory landscape, facilitating compliance and safeguarding sensitive information.