The future of host cell protein (HCP) identification during process development and manufacturing linked to a risk-based management for their control.
The future of host cell protein (HCP) identification during process development and manufacturing linked to a risk-based management for their control.
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DOI：
10.1002/bit.25628
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发表时间：
2015-09
影响因子：
3.8
通讯作者：
Smales CM
中科院分区：
文献类型：
--
作者：
Bracewell DG;Francis R;Smales CM
利用生物系统合成复杂的治疗产品已经取得了显著的成功。然而，在产品开发过程中，必须非常重视定义来自该生物系统的可接受杂质水平，该列表的标题是宿主细胞蛋白（HCPs）。蛋白质组学分析的最新进展显示了这类杂质的多样性；随着这些知识和能力的增长，不可避免地出现了一些问题，即当前测量hcp的方法是否彻底。根本问题是如何充分测量（并反过来监测和控制）如此大量的蛋白质种类（可能有数千种成分），以确保安全有效的产品。一种相当优雅的解决方案是使用免疫测定法（酶联免疫吸附测定法[ELISA]），该方法基于针对宿主细胞（生物系统）的多克隆抗体，用于合成特定的治疗产品。然而，测量完全取决于所使用的抗体血清，这决定了测定的敏感性和HCP谱的覆盖程度。它提供了一个HCP量的总和模拟值；如果所有HCP成分可以被认为是相同的，则为阳性；如果HCP蛋白质组的某些成分更有可能导致更高的风险，则为阴性。在一个彻底的基于风险的方法中，人们希望能够解释这一点。这些问题导致了正交分析方法的研究；最突出的是质谱分析。这些技术可以潜在地识别和量化hcp。测量和监测数千种蛋白质的能力按比例增加了获得的数据量。如果这些信息可以用来确定关键的hcp，从而为风险管理创造一个改进的基础，那么就会产生重大的好处。我们描述了一种基于此类数据的新兴的hcp风险评估方法，提请注意与生物仿制药计划相关的及时性。这种方法的开发需要基于多种风险因素累积知识的数据库，这将需要国家和国际监管机构、标准当局（例如，NIST和NIBSC）、工业界和学术界都参与制定采用最新生物分析技术的最佳方法，这对于提供安全有效的所有类型的生物药物至关重要。Biotechnol。Bioeng。2015;112: 1727 - 1737。©2015作者。《生物技术与生物工程》，Wiley期刊公司出版。
The use of biological systems to synthesize complex therapeutic products has been a remarkable success. However, during product development, great attention must be devoted to defining acceptable levels of impurities that derive from that biological system, heading this list are host cell proteins (HCPs). Recent advances in proteomic analytics have shown how diverse this class of impurities is; as such knowledge and capability grows inevitable questions have arisen about how thorough current approaches to measuring HCPs are. The fundamental issue is how to adequately measure (and in turn monitor and control) such a large number of protein species (potentially thousands of components) to ensure safe and efficacious products. A rather elegant solution is to use an immunoassay (enzyme‐linked immunosorbent assay [ELISA]) based on polyclonal antibodies raised to the host cell (biological system) used to synthesize a particular therapeutic product. However, the measurement is entirely dependent on the antibody serum used, which dictates the sensitivity of the assay and the degree of coverage of the HCP spectrum. It provides one summed analog value for HCP amount; a positive if all HCP components can be considered equal, a negative in the more likely event one associates greater risk with certain components of the HCP proteome. In a thorough risk‐based approach, one would wish to be able to account for this. These issues have led to the investigation of orthogonal analytical methods; most prominently mass spectrometry. These techniques can potentially both identify and quantify HCPs. The ability to measure and monitor thousands of proteins proportionally increases the amount of data acquired. Significant benefits exist if the information can be used to determine critical HCPs and thereby create an improved basis for risk management. We describe a nascent approach to risk assessment of HCPs based upon such data, drawing attention to timeliness in relation to biosimilar initiatives. The development of such an approach requires databases based on cumulative knowledge of multiple risk factors that would require national and international regulators, standards authorities (e.g., NIST and NIBSC), industry and academia to all be involved in shaping what is the best approach to the adoption of the latest bioanalytical technology to this area, which is vital to delivering safe efficacious biological medicines of all types. Biotechnol. Bioeng. 2015;112: 1727–1737. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.