The University of North Carolina at Chapel Hill, 160 Medical Drive, Chapel Hill, North Carolina, USA.
Toxicol Pathol. 2023 Jan;51(1-2):77-80. doi: 10.1177/01926233231163474. Epub 2023 Apr 21.
Nonclinical toxicity testing (GLP) of prophylactic vaccines to support human clinical trials is outlined in the World Health Organization nonclinical vaccine-development guidelines, which are followed by most regulatory agencies globally. Vaccine GLP toxicity studies include at least two groups: a buffer control (often phosphate-buffered saline) group and a highest anticipated clinical dose formulation group. However, studies may include additional groups, including lower-dose formulation groups and adjuvant-containing formulation control groups. World Health Organization guidelines touch upon expectations for dose group and tissue selection for microscopic evaluation, but there is variation in the interpretation of this aspect of these guidelines between vaccine developers. This opinion piece proposes a scientifically based approach for defining appropriate groups to evaluate in the dosing and recovery phases in nonclinical vaccine toxicity studies, as well as suggestions on selecting tissues for microscopic evaluation at the recovery phase of studies to promote alignment between vaccine manufacturers.
支持人体临床试验的预防性疫苗的非临床毒理学测试（GLP）概述于世界卫生组织非临床疫苗开发指南中，该指南被大多数全球监管机构所遵循。疫苗 GLP 毒性研究至少包括两组：缓冲对照（通常为磷酸盐缓冲盐水）组和最高预期临床剂量制剂组。然而，研究可能包括其他组，包括低剂量制剂组和含有佐剂的制剂对照组。世界卫生组织指南涉及对剂量组和组织选择进行微观评估的预期，但疫苗开发者对这些指南这一方面的解释存在差异。本文提出了一种基于科学的方法，用于定义在非临床疫苗毒性研究的剂量和恢复期评估中适当的组别，并就研究恢复期的微观评估选择组织提供建议，以促进疫苗制造商之间的一致性。
