Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transparency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combinations are not discussed in this paper). Emphasis is placed on considerations for structuring a compliant drug-device stability program, including the use of bracketing and matrixing the test schedule to support the establishment of the product expiry date and how legacy products can be evaluated to meet current standards.

中文翻译：

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药物器械组合产品的稳定性考虑 - 21 CFR 第 4 部分更新

组合产品是包含以下两项或多项的治疗和诊断产品：药物、生物制品和设备。这些产品是提高临床疗效所必需的，并且具有不止一种作用方式 (MOA)。因此，它们需要更复杂的监管途径并遵守至少两 (2) 套监管标准。2013 年，联邦法规 (CFR) 第 21 章第 4 部分发布，以阐明在包含药物、器械或生物制品时适用的 GMP 法规。FDA（美国食品和药物管理局）在 2017 年发布了额外的指南，以简化监管框架，并在多个监管标准重叠时提供关于证明 GMP 合规性的透明度。本文总结了药物器械组合产品的现行良好生产规范 (CGMP) 要求（本文未讨论生物组合）。重点放在考虑构建合规的药物器械稳定性计划，包括使用括号和矩阵测试计划来支持产品有效期的建立以及如何评估遗留产品以满足当前标准。