Medicines and Healthcare products Regulatory Agency, London, UK.
Medicines and Healthcare products Regulatory Agency, London, UK.
Reprod Toxicol. 2020 Apr;93:199-210. doi: 10.1016/j.reprotox.2020.02.011. Epub 2020 Feb 29.
The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal development and the prediction of potential risks associated with the use of medicines in pregnancy. A workshop organised by the Medicines and Healthcare products Regulatory Agency (MHRA), "Predicting the Safety of Medicines in Pregnancy - a New Era?", was attended by delegates representing regulatory authorities, academia, industry, patients, funding bodies and software developers to consider how to improve the quality of and access to nonclinical developmental toxicity data and how to use this data to better predict the safety of medicines in human pregnancy. The workshop delegates concluded that based on comparative data to date alternative methodologies are currently no more predictive than conventional methods and not qualified for use in regulatory submissions. To advance the development and qualification of alternative methodologies, there is a requirement for better coordinated multidisciplinary cross-sector interactions coupled with data sharing. Furthermore, a better understanding of human developmental biology and the incorporation of this knowledge into the development of alternative methodologies is essential to enhance the prediction of adverse outcomes for human development. The output of the workshop was a series of recommendations aimed at supporting multidisciplinary efforts to develop and validate these alternative methodologies.
发育毒性测试的框架在过去 50 多年中基本保持不变，尽管它在评估妊娠期间的潜在风险方面仍然非常有价值，但仍存在知识差距，并且某些结果不一定与临床经验相关。组学、计算方法和替代检测方法的进步为增强我们对胚胎-胎儿发育的理解以及预测与妊娠期间使用药物相关的潜在风险提供了机会。药品和医疗产品监管机构 (MHRA) 组织的一次研讨会，题为“预测妊娠期间药物的安全性——新时代？”，代表监管机构、学术界、工业界、患者、资助机构和软件开发人员的代表参加了此次研讨会，以探讨如何提高非临床发育毒性数据的质量和可及性，以及如何利用这些数据更好地预测妊娠期间药物的安全性。研讨会代表得出的结论是，基于迄今为止的比较数据，替代方法目前并不比传统方法更具预测性，不具备在监管提交中使用的资格。为了推进替代方法的开发和资格认证，需要更好地协调跨部门的多学科交叉互动，并进行数据共享。此外，更好地了解人类发育生物学并将这方面的知识纳入替代方法的开发中，对于提高对人类发育不良结局的预测至关重要。研讨会的成果是一系列建议，旨在支持多学科努力开发和验证这些替代方法。
