口服固体制剂连续制造物料处理考虑及监管检查要点探讨

Considerations on Material Handling and Regulatory Inspection Key Points for Continuous Manufacturing of Oral Solid Dosage Forms

随着人用药品技术要求国际协调理事会(ICH)Q13指南的发布以及多个采用连续制造技术的口服固体制剂获批,药品连续制造在该类产品领域的监管发展受到越来越多的关注。物料处理是连续制造平台重要的组成部分,本研究分析了物料输入、连续给料和连续混合方面的技术特点,介绍了口服固体制剂连续制造的物料处理步骤,并从工艺验证、稳健性、设施设备、过程控制、质量保证和清洁等方面探讨了监管检查的关注点。在相关技术考量方面,工艺设备应能持续稳定地传递物料且尽可能控制风险并降低物料损耗,因此需要深入了解物料特性,科学地设计工艺设备和开展确认验证;在监管检查方面可关注连续工艺的专属风险以及对产品质量可能产生的影响。期望能以此促进连续制造在制药行业的应用,同时也建议监管机构、制药企业以及全社会共同参与,充分运用过程分析技术、创新检验方法和数字化质量保证等手段助力持续生产出符合质量要求的产品,从而推动我国制药工业向高水平现代化迈进。

With the release of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH)Q13 guideline and the approval of several oral solid dosage form drug products adopting continuous manufacturing techniques,the regulatory development in this area is receiving increasing attention.Material handling is an important part of a continuous manufacturing platform.In this paper,the material handling for continuous manufacturing of oral solid dosage forms is introduced through analyzing the technical characteristics of material input,continuous feeding and continuous mixing.Also,the concerns of supervision and inspection are studied from the aspects of process validation,robustness,facilities and equipment,process control,quality assurance and cleaning.For technical consideration,process equipment should handle materials continuously and stably,with risks controlled and losses reduced as much as possible,so it is necessary to have a deep understanding of material characteristics,scientifically design process equipment and carry out qualification and verification;while regulatory inspections may focus on continuous process-specific risks and their possible effects on product quality.Hopefully this paper could accelerate the application of continuous manufacturing in pharmaceutical industry together with the aid of cooperation of regulation agencies,industrial community as well as the whole society,making full use of process analysis technology,innovative testing methods and digital quality assurance to steadily manufacture qualified products,thus promote domestic pharmaceutical industry to a high level of modernization.