The most common approach for the manufacture of oligonucleotides includes isolation of the active pharmaceutical ingredient (API) via lyophilization to provide a solid product, which is then dissolved to provide an aqueous formulation. It is well known from the development and manufacture of large molecules (“biologics”) that API production does not always require isolation of solid API before drug product formulation, and this article provides technical considerations for the analogous use of oligonucleotide API in solution. The primary factor considered is solution stability, and additional factors such as viscosity, concentration, end-to-end manufacturing, microbiological control, packaging, and storage are also discussed. The technical considerations discussed in this article will aid the careful evaluation of the relative advantages and disadvantages of solution versus powder API for a given oligonucleotide drug substance.

中文翻译：

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使用寡核苷酸溶液 API 的技术注意事项。

制造寡核苷酸的最常见方法包括通过冻干分离活性药物成分 (API) 以提供固体产品，然后将其溶解以提供水性制剂。从大分子（“生物制剂”）的开发和制造中众所周知，API 生产并不总是需要在制剂前分离固体 API，本文提供了在溶液中类似使用寡核苷酸 API 的技术考虑。考虑的主要因素是溶液稳定性，另外还讨论了粘度、浓度、端到端制造、微生物控制、包装和储存等其他因素。