The Oligonucleotide Working Group of the European Federation of Pharmaceutical Industries and Associations (EFPIA) conducted a survey of companies to understand the trends in nonclinical practices and regulatory expectations for oligonucleotide drug safety assessment. Twenty-two companies of different types, with varying oligonucleotide experience levels in the field, participated. The survey identified key regulatory challenges and areas of perceived health authority (HA) concern regarding nonclinical safety strategies for oligonucleotides, such as the choice of toxicology species, approaches to dose setting in toxicity studies, dose scaling from animals to humans, the implementation (and regulatory acceptability) of lean packages, and methods for dealing with impurities and human-specific off-targets. The perceived oligonucleotide experience of HAs and the relevance of guidance to oligonucleotide development were also assessed. The results showed a general lack of consensus on nonclinical safety assessment approaches being used for this growing class of medicines and highlight the need for continuing collaboration between sponsors and HAs to better define best practices.

中文翻译：

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欧洲制药工业和协会联合会寡核苷酸工作组关于治疗性寡核苷酸安全性评估的非临床实践和监管期望调查的结果

欧洲制药工业和协会联合会 (EFPIA) 的寡核苷酸工作组对公司进行了一项调查，以了解非临床实践的趋势和对寡核苷酸药物安全性评估的监管期望。22 家不同类型、在该领域具有不同寡核苷酸经验水平的公司参加了此次会议。该调查确定了有关寡核苷酸非临床安全策略的关键监管挑战和感知卫生当局 (HA) 关注的领域，例如毒理学物种的选择、毒性研究中的剂量设定方法、从动物到人类的剂量缩放、实施（和监管可接受性），以及处理杂质和人类特定脱靶的方法。还评估了 HA 的感知寡核苷酸经验以及指导与寡核苷酸开发的相关性。结果表明，对于用于此类不断增长的药物类别的非临床安全性评估方法普遍缺乏共识，并强调了申办者和 HA 之间继续合作以更好地定义最佳实践的必要性。