Reference Standard Characterization and Management

Element的完整参考标准管理程序支持小分子药物, 生物制剂和生物类似物的结构和纯度的参考标准表征, periodic requalification, and reference standard storage and distribution.

合格的参考标准品作为有效的基线材料，以满足纯度的法规要求, 既要确认药品的纯度，又要证明对产品相关杂质的控制.g., product degradation) and analytical method performance. Furthermore, 制造商依靠合格的参考标准来评估生产工艺变更对药品的影响, as well as for overcoming challenges that arise during manufacturing. 在药物开发的早期对参比标准进行彻底和严格的表征, 随着产品发展到后期，投资将获得回报, resulting in a significant impact on improved final product quality. Reference standard qualification, development, 表征和管理对于提供安全有效的治疗方法至关重要，可以经得起监管审查.

Non-compendial reference standard development services

Some well-characterized, high purity (>99.5%) compendial reference standards, also referred to as primary reference standards, are available for purchase from pharmacopoeias. Alternatively, in the absence of a readily available official source, 必须遵循FDA提供的监管指南来建立作为参考标准的化学品. When developing and characterizing new reference standards, 需要考虑和克服几个挑战和考虑因素, including operational efficiency and reliability. 药物开发人员发现，在临床前和临床开发过程中，药典参考标准可能无法获得，这并不罕见, 包括第一阶段批释放和第二阶段和/或第三阶段杂质测试. 对于大多数大分子和先进的生物治疗药物来说尤其如此.

The synthesis, characterization, 新的非药典参考标准的鉴定和管理对内部制药团队来说可能是一个挑战. Element的知识渊博的科学家团队在成功合成方面有着良好的记录, 作为专有化合物的结果，表征和鉴定非药典参考标准, generic drug applications, extractables and leachables studies, 以及其他一些药典参考标准不容易获得的情况.

Reference standard requalification, storage and distribution

Typically, annual requalification is recommended for reference standards, however, depending on how the reference standard is put to use, 再确认的分析程序可能比初始确认过程较少涉及. 用于化学鉴定的参考标准通常要求不那么严格的再鉴定, 包括使用NMR或FT-IR进行识别测试，并将该数据与初始表征过程中生成的初始数据集进行比较. 同样，如果标准品用于纯度测试，则必须重新分配纯度. 由于吸湿和降解的风险，需要进行全纯度测试.

In addition to requalification services, Element offers storage and distribution services, 对于没有能力或意愿存储参考资料的虚拟制药公司来说，哪些是特别有价值的. 所有参考标准管理程序均遵守GMP程序, including proper storage conditions, requalification schedules and shipment.

Biologics and biosimilars reference standard characterization

生物制药药物具有比小分子药物更复杂的结构, and full characterization is often not achievable. Therefore, a broad range of analytical tests (e.g., 以细胞为基础的效价法和色谱法经常用于评估活性成分和药品的质量属性, including characterization, comparability, lot release and confirmation of stability. Reference standards calibrate and confirm the suitability of these tests, 并通过建立原始生物制品或生物仿制药的标准理化概况，为后续测试提供基准.

在可能的情况下，使用药典标准作为主要参考标准. However, in-house reference standards are established for various purposes, 包括测定生物活性的定量比较分析方法, qualitative analytical methods for purity testing, and performance control assays to evaluate system suitability. In-house reference standards are also used for batch release, stability, characterization studies and comparability assessments. ICH Q6B概述了生物制剂参考标准的一般监管期望, Q2(R1), 和Q7A，在制定和应用参考标准时应予以考虑.

Element’s deep understanding of the regulatory landscape, 成功克服了复杂大分子产品开发的独特挑战, 深入的科学专业知识奠定了我们为生物制剂和生物类似药提供全面参考标准鉴定服务的基础, tailored to meet the specific needs of your product. Ensure reference standards are appropriately stable, suitable for their purpose, qualified according to schedule, 并代表Element作为CDMO合作伙伴在关键临床研究中使用的任何适用的既往参考标准材料.

The Element advantage

通过Element的参考标准表征，自信地满足法规要求, 为满足你们药品的独特需求而定制的认证和管理程序. To learn about our complete reference standard qualification, characterization, and management programs for pharmaceuticals, biologics, and biosimilars, or to speak with one of our experts, contact us today.