Bayer Pharmaceuticals, Berkeley, California, USA.
Biotechnol Prog. 2024 Jul-Aug;40(4):e3461. doi: 10.1002/btpr.3461. Epub 2024 Apr 1.
Biopharmaceutical manufacturing entails a series of highly regulated steps. The manufacturing of safe and efficacious drug product (DP) requires testing of critical quality attributes (CQAs) against specification limits. DP potency concentration, which measures the dosage strength of a particular DP, is a CQA of great interest. In order to minimize the DP potency out-of-specification (OOS) risk, sterile fill finish (SFF) process adjustments may be needed. Varying the potency targets can be one such process adjustment. To facilitate such evaluation, data acquisition and statistical calculations are required. Regularly conducting the OOS risk assessment manually using commercial statistical software can be tedious, error-prone, and impractical, especially when several alternate potency targets are under consideration. In this work, the development of a novel framework for OOS risk assessment and deployment of cloud-based statistical software application to facilitate the risk assessment are presented. This application is intended to streamline the assessment of alternate potency targets for DP in biologics manufacturing. The major aspects of this potency targeting application development are presented in detail. Specifically, data sources, pipeline, application architecture, back-end and front-end development as well as application verification are discussed. Finally, several use cases are presented to highlight the application's utility in biologics manufacturing.
生物制药生产需要经过一系列高度监管的步骤。为了生产安全有效的药物产品（DP），需要根据规格限制对关键质量属性（CQA）进行测试。DP 效价浓度是一个非常重要的 CQA，它衡量特定 DP 的剂量强度。为了最大限度地降低 DP 效价超出规格（OOS）的风险，可能需要对无菌灌装完成（SFF）工艺进行调整。改变效价目标就是一种这样的工艺调整。为了方便进行这种评估，需要进行数据采集和统计计算。使用商业统计软件手动定期进行 OOS 风险评估可能既繁琐又容易出错，而且不切实际，尤其是在考虑多个替代效价目标时。在这项工作中，提出了一种用于 OOS 风险评估的新框架，并部署了基于云的统计软件应用程序来方便风险评估。该应用旨在简化生物制药中 DP 的替代效价目标的评估。详细介绍了该效价目标应用程序开发的主要方面。具体来说，讨论了数据源、管道、应用程序架构、后端和前端开发以及应用程序验证。最后，提出了几个用例来突出该应用程序在生物制药生产中的实用性。
