Novartis, Lichtstrasse 35, Basel, 4056, Switzerland.
Amgen Inc, Los Angeles, California, USA.
Br J Clin Pharmacol. 2024 Mar;90(3):715-721. doi: 10.1111/bcp.15920. Epub 2023 Nov 15.
Globally, more than 200 million women become pregnant each year, most of whom receive medications despite limited information on their safe use during pregnancy. The paucity of drug safety data on pregnant and breastfeeding women stems from the routine exclusion of this population from clinical trials due to scientific, ethical, regulatory and legal concerns. Consequently, at the time of initial drug approval, there may be scant safety data to inform the drug benefit-risk balance to the mother, foetus or infant. Although momentum is growing to include this underrepresented population in clinical trials, most information on drug exposure outcomes comes from data collected in the postmarketing setting. Regulatory guidance and legislation on medication use in pregnancy and breastfeeding were reviewed globally by the TransCelerate IGR PV Pregnancy and Breastfeeding Team. The International Conference of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) standards and Council for International Organizations of Medical Sciences guidelines served as benchmarks for national safety regulations and guidance. The landscape assessment identified a lack of harmonization of global regulations on research in pregnant and breastfeeding women and a lack of specific regulations on this topic in the majority of the territories included in the assessment. This article focuses on the ambiguities and lack of harmonization in global regulations on postmarketing pregnancy and breastfeeding safety studies. There is currently no ICH standard to guide these types of safety studies and, in most regions reviewed, there are no clear regulations or guidance on when and how to conduct them. While a challenging undertaking, greater clarity and harmonization would facilitate more timely completion of postmarketing pregnancy safety studies that would ultimately generate the critical data needed to optimize benefit-risk decisions for women who may conceive, as well as pregnant and breastfeeding women.
全球每年有超过 2 亿女性怀孕，其中大多数人在怀孕期间都会接受药物治疗，但关于这些药物在孕期使用的安全性信息却十分有限。造成这种情况的原因是，出于科学、伦理、监管和法律方面的考虑，这一人群往往被排除在临床试验之外。因此，在最初批准药物时，可能几乎没有安全性数据来告知母亲、胎儿或婴儿药物的获益-风险平衡。尽管越来越多的人呼吁将这一人群纳入临床试验，但大多数关于药物暴露结果的数据都来自上市后收集的数据。TransCelerate IGR PV 妊娠和哺乳期团队在全球范围内审查了关于妊娠和哺乳期用药的监管指南和立法。国际人用药品注册技术协调会（ICH）标准和国际医学组织理事会（CIOMS）指南被用作国家安全性法规和指南的基准。该景观评估发现，全球关于妊娠和哺乳期妇女研究的监管缺乏协调统一，而且在评估中所包含的大多数地区，针对这一主题缺乏具体的监管规定。本文重点讨论了全球关于上市后妊娠和哺乳期安全性研究的监管规定中的模糊性和缺乏协调统一的问题。目前，没有 ICH 标准来指导这类安全性研究，在大多数审查的地区，对于何时以及如何进行这些研究，也没有明确的规定或指南。虽然这是一项具有挑战性的任务，但增加明确性和协调统一性将有助于更及时地完成上市后妊娠安全性研究，最终为可能怀孕的妇女以及妊娠和哺乳期妇女做出获益-风险决策提供所需的关键数据。
