Dr. Naresh Sharma, Deputy Drugs Controller (India), CDSCO
In a workshop hosted by the Central Drugs Standard Control Organization (CDSCO) and FDCA in association with the Indian Drug Manufacturers Association (IDMA), Dr. Naresh Sharma, Deputy Drugs Controller (India), highlights the importance of vendor audits, the role of excipients with the revised schedule M and also elaborates best practices for vendors to adhere to.
Effective from 2025, the DCGI (Drug Controller General of India) is working diligently to implement these changes for the betterment of the industry. This revision aligns with global standards, incorporating WHO TRS (Technical Report Series) guidelines directly into Indian regulations. Over time, as WHO updates its standards, Indian manufacturers will adopt these changes, ensuring compliance with international norms.
Compliance with Schedule M is non-negotiable. Implementing these standards will position us to gain a significant competitive edge. GMP requirements, which apply to both human and animal products, extend to vendor audits and qualification processes, covering APIs (Active Pharmaceutical Ingredients), excipients, and packaging materials.
Quality is a relentless commitment to the continuous improvement of products, processes, and systems. Meeting global requirements for consistent quality necessitates a focus on raw materials, excipients. Schedule M is not just a regulatory mandate but an opportunity for Indian pharmaceutical companies to elevate their standards to meet global expectations.
Excipients and raw materials are integral to pharmaceutical formulations, playing a significant role in determining the quality, efficacy, and safety of medicines. Excipients, often perceived as inactive ingredients, directly influence the stability, bioavailability, and performance of a drug. Rigorous testing during product development ensures that the concentration is justified. For instance, when a formulation incorporates 1% of a dissolution enhancer, manufacturers must validate whether concentrations like 0.5% or 2% offer comparative or superior benefits. This validation is crucial to optimizing safety and therapeutic efficacy.
Manufacturers must meticulously document every step of product development, including stability studies, bioavailability assessments, and bioequivalence data. A culture of quality, reinforced by continuous training, is essential to maintaining compliance with Good Manufacturing Practices (GMP). Workshops, such as those conducted by EDMA, emphasize embedding quality practices across all levels of production, from raw material sourcing to the final product.
The Revised Schedule M guidelines stress the importance of vendor qualification, especially for raw materials, including excipients. Even minor changes in raw material characteristics can have profound effects on the final product. A notable example involved an API synthesis process modification that significantly reduced dissolution rates, underscoring the necessity of strict supplier agreements and monitoring systems to address changes proactively. Similarly, the choice of different optical forms of APIs can alter bioavailability and therapeutic outcomes, despite meeting standard pharmacopeial tests. Manufacturers must perform in-depth literature reviews and technical evaluations to ensure the suitability of new raw materials.
Discrepancies in regulatory standards across regions also pose challenges. A case involving calcium leucovorin injection> demonstrated how variations in endotoxin limits between Indian and U.S. pharmacopeias created compliance issues. Although the product met Indian standards, it failed U.S. requirements. By adhering to the stricter standard, the manufacturer prioritized global uniformity and patient safety, exemplifying the importance of adopting rigorous quality benchmarks.
Excipients significantly affect not only drug formulations but also manufacturing processes. For example, a change in the supplier for PEG 300, an excipient used in etoposide injection, led to a rise in impurities in the final product. Despite meeting standard specifications, variations in the pH of the excipient altered the manufacturing process, resulting in higher impurity levels. Such cases highlight the importance of close monitoring and understanding the interactions between excipients and specific manufacturing conditions.
The pharmaceutical industry must adopt a holistic approach to ensure the quality and reliability of its products. This involves treating APIs and excipients with equal rigor, conducting robust vendor qualifications, and adhering to stringent specifications. Comprehensive documentation of changes and a commitment to continuous improvement are essential to maintaining global compliance. By fostering a culture of excellence, manufacturers can consistently deliver high-quality medications, ensuring safety and efficacy for patients worldwide.
The revised Schedule M is not just a regulatory mandate but an opportunity for Indian pharmaceutical companies to elevate their standards to meet global expectations. By focusing on dedicated production lines, mastering a limited number of products, and adhering to stringent quality practices, we can ensure that Indian medicines continue to make a significant impact on global health.
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