Steinwandter Valentin, Herwig Christoph
Exputec GmbH, Mariahilferstr. 147/2/2D, Vienna, Austria.
Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna University of Technology, Gumpendorferstr. 1a, Vienna, Austria; and
PDA J Pharm Sci Technol. 2019 Jul-Aug;73(4):373-390. doi: 10.5731/pdajpst.2018.009407. Epub 2019 Feb 15.
In the pharmaceutical industry, process validation tasks are based on the raw data and its derived analytical results generated from the process. Process validation failure affects both patient safety and the economic success of the manufacturing company. Hence, data integrity is highly critical in this area. Regulatory agencies, such as the Food and Drug Administration (FDA), reacted to past data integrity breaches by publishing new guidelines on data integrity for the correct handling of data in the pharmaceutical context.In this contribution, we want to show how data integrity can be improved on a technological level, removing the need for trusted third parties and centralized systems for this task. Therefore, we implemented an approach that uses existing tools, currently mostly used by software developers, and combined them with a new smart contract built on top of the Ethereum blockchain. In a case study, we test how data manipulation or backdating of results can be easily detected and how regulatory agencies can audit the complete data flow from the regulatory report back to the original raw data.The results of this contribution outline a possible road map for the development of production-ready tools, such as versioned database systems that natively interoperate with distributed ledgers. This will improve the trustworthiness of pharmaceutical manufacturing data by both protecting the intellectual property of the industrial company and improving the safety of the patients. In the pharmaceutical industry, economically driven manufacturing companies are regulated and controlled by regulatory agencies. The pharmaceutical manufacturing companies need to produce large amounts of process and analytical data to show that their products are safe for patients. As the decisions of the regulatory agencies rely on this data, manufacturing companies need to prove how their generated data can be protected from technical breaches or data manipulation.As of today, the available technical solutions to provide data integrity are not working well enough. Regulatory agencies have published multiple documents highlighting the current data integrity issues.In this contribution, we show how blockchain, a technology that multiple cryptocurrencies like Bitcoin rely on, can help to improve the integrity of manufacturing data and data science analysis procedures. Therefore, we combined a smart contract on the Ethereum blockchain with tools currently mostly used by software developers. The presented workflow shows how data integrity can be guaranteed on a technological level without the need for trusted third parties.
在制药行业，工艺验证任务基于生产过程中产生的原始数据及其派生的分析结果。工艺验证失败会影响患者安全和制造公司的经济成功。因此，数据完整性在这一领域至关重要。监管机构，如美国食品药品监督管理局（FDA），针对过去的数据完整性违规行为发布了有关制药领域数据正确处理的数据完整性新指南。
在本论文中，我们想展示如何在技术层面上提高数据完整性，无需可信第三方和集中式系统来完成此任务。因此，我们实施了一种方法，该方法使用软件开发人员目前大多使用的现有工具，并将它们与基于以太坊区块链构建的新智能合约相结合。在一个案例研究中，我们测试了如何轻松检测结果的数据操纵或倒签日期，以及监管机构如何审核从监管报告到原始原始数据的完整数据流。
本论文的结果勾勒了开发可用于生产的工具（如与分布式账本原生互操作的版本化数据库系统）的可能路线图。这将通过保护工业公司的知识产权和提高患者安全性来提升制药制造数据的可信度。在制药行业，受经济驱动的制造公司受到监管机构的监管和控制。制药制造公司需要生成大量的工艺和分析数据，以证明其产品对患者是安全的。由于监管机构的决策依赖于这些数据，制造公司需要证明如何保护其生成的数据免受技术违规或数据操纵的影响。
截至目前，现有的提供数据完整性的技术解决方案效果不佳。监管机构已发布多份文件强调当前的数据完整性问题。
在本论文中，我们展示了区块链（比特币等多种加密货币所依赖的技术）如何有助于提高制造数据和数据科学分析程序的完整性。因此，我们将以太坊区块链上的智能合约与软件开发人员目前大多使用的工具相结合。所展示的工作流程表明，无需可信第三方即可在技术层面保证数据完整性。
