圈养毒蛇的良好管理实践,以生产基于生物毒液的药物:实现可重复性并为制药行业做出贡献。

Good management practices of venomous snakes in captivity to produce biological venom-based medicines: achieving replicability and contributing to pharmaceutical industry.

机构信息

Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP) , Botucatu, Brazil.

Graduate Program in Tropical Diseases, Botucatu Medical School (FMB), São Paulo State University (UNESP) , Botucatu, Brazil.

出版信息

J Toxicol Environ Health B Crit Rev. 2021 Jan 2;24(1):30-50. doi: 10.1080/10937404.2020.1855279. Epub 2020 Dec 14.

Abstract

One of the factors responsible for lack of reproducible findings may be attributed to the raw material used. To date, there are no apparent studies examining reproducibility using venoms for the development of new toxin-based drugs with respect to regulatory agencies' policies. For this reason, protocols were implemented to produce animal toxins with quality, traceability, and strict compliance with Good Manufacturing Practices. This required validation of the production chain from the arrival of the animal to the vivarium, followed by handling, housing, as well as compliance with respect to extraction, freeze-drying, and, finally, storage protocols, aimed at generating compounds to serve as candidate molecules applicable in clinical trials. Currently, to produce quality snake venoms to support reproductive studies, the Center for the Study of Venoms and Venomous Animals (CEVAP) from São Paulo State University (UNESP), São Paulo, Brazil has 449 microchipped snakes through rigid and standardized operating procedures for safety, health, and welfare of animals. Snakes were frequently subjected to vet clinical examination, anthelmintic, and antiparasitic treatment. Venom milk used to destroy prey was collected from each animal in individual plastic microtubes to avoid contamination and for traceability. In addition, venoms were submitted to microbiological, and biochemical toxicological analyses. It is noteworthy that investigators are responsible for caring, maintaining, and manipulating snakes and ensuring their health in captivity. This review aimed to contribute to the pharmaceutical industry the experimental experience and entire snake venom production chain required to generate quality products for therapeutic human consumption.

摘要

导致重现性结果缺乏的因素之一可能归因于所用的原材料。迄今为止,尚无明显的研究检查使用毒液来开发新的基于毒素的药物的重现性,这与监管机构的政策有关。出于这个原因,制定了生产具有质量、可追溯性和严格符合良好生产规范的动物毒素的方案。这需要从动物到达养殖场开始,对生产链进行验证,然后进行处理、饲养,以及遵守提取、冷冻干燥和最终储存方案,旨在生成化合物作为适用于临床试验的候选分子。目前,为了生产高质量的蛇毒液来支持重现性研究,巴西圣保罗州立大学毒液和毒蛇研究中心 (CEVAP) 拥有 449 条经过微芯片标记的蛇,这些蛇采用严格的标准化操作规程,以确保动物的安全、健康和福利。蛇经常接受兽医临床检查、驱虫和驱虫治疗。从每只动物的单独塑料管中收集用于破坏猎物的毒液奶,以避免污染和可追溯性。此外,毒液还经过微生物学和生物化学毒理学分析。值得注意的是,研究人员负责照顾、维护和操作蛇,并确保其在圈养中的健康。本综述旨在为制药行业提供实验经验和整个蛇毒液生产链,以生成高质量的产品供人类治疗使用。

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