First Principles Biopharma, LLC, Louisville, CO, USA.
Similis Bio, JSR Life Sciences, LLC, Sunnyvale, CA, USA.
J Pharm Sci. 2024 Nov;113(11):3123-3136. doi: 10.1016/j.xphs.2024.09.013. Epub 2024 Sep 21.
The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability. Significant R&D CMC work continues post-approval to support continuous improvement and market expansion of the commercial product. These activities are crucial elements of Product Lifecycle Management, and taken together, they comprise Pharmaceutical Quality or Chemistry, Manufacturing and Controls (CMC). The objective of this paper is to mitigate the regulatory ambiguity of R&D quality systems with practical, risk-based examples and recommendations when conducting supportive CMC studies for biological products. Making sound strategic CMC decisions under any circumstances assumes data from R&D studies are reliable, traceable, and complete. While there are specific regulatory guidelines on phase-appropriate cGMP activities, none exist for quality practices in R&D CMC laboratories conducting non-cGMP studies. Hindsight is not the time to discover that R&D studies lack key elements that would otherwise have allowed the data to be directly presented to regulators, if needed. There is a strong prospective business interest in protecting considerable investments made for CMC R&D studies. Therefore, establishment of a robust and stage-appropriate R&D laboratory quality system is essential for companies seeking to capitalize on prior knowledge, protect investments, and be prepared for accelerated approval pathways.
药品开发是将潜在新药从学术发现转化为患者实际治疗的关键环节。它将新药的创意转化为如何制造、配方、表征和控制药物，以用于非临床和早期临床试验的实验室研究。从临床前研发发现工作到商业发布，都会产生大量的研发 CMC 数据，用于开发和优化 cGMP 制造和测试操作，同时支持产品可比性、阐明产品/杂质结构、评估关键质量属性、开发药物输送模式以及为长期稳定性开发产品配方。在批准后，还会进行大量的研发 CMC 工作，以支持商业产品的持续改进和市场扩张。这些活动是产品生命周期管理的关键要素，它们共同构成了医药质量或化学、制造和控制（CMC）。本文的目的是通过实际的、基于风险的例子和建议，减轻研发质量体系的监管模糊性，为生物制品进行支持性 CMC 研究。在任何情况下，做出明智的战略 CMC 决策都假设研发研究的数据是可靠的、可追溯的和完整的。虽然有关于适当阶段 cGMP 活动的具体监管指南，但对于进行非 cGMP 研究的研发 CMC 实验室的质量实践，没有相关规定。事后才发现研发研究缺乏关键要素，这会导致数据无法直接提交给监管机构，这并不是明智之举。在 CMC 研发研究方面进行有前瞻性的商业投资，保护这些投资是非常重要的。因此，建立一个强大且适合各阶段的研发实验室质量体系，对于寻求利用现有知识、保护投资并为加速审批途径做好准备的公司来说至关重要。
