Purpose

The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations.

Methods

Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020.

Results

We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug’s recommended pH range, concentration ranges for excipients, and route of administration.

Conclusions

The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.

中文翻译：

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对目前市售的治疗性生物药品中使用的辅料进行全面的科学调查。

 目的

过去几十年来，生物技术衍生的治疗性生物制剂的稳步发展已经产生了一些药物，这些药物现在已成为一系列适应症的标准医疗方法。虽然蛋白质产品的开发近年来激增，但这些复杂分子的配方和递送依赖于药物特异性研究，在某些情况下还依赖于非蛋白质药物产品的数据。由于许多制剂的药物特异性，用于支持治疗性蛋白质开发的赋形剂技术的共性、趋势和差距在很大程度上仍未得到探索。

 方法

我们使用全面的关系数据库方法，旨在对所有已批准或许可的生物技术衍生药物产品进行科学调查，目的是提供有关蛋白质产品辅料的共同属性和趋势特征的循证信息。截至 2020 年 6 月，我们检查了 665 种配方和 395 种基于独特赋形剂的独特配方，支持 211 种治疗性蛋白质。

 结果

我们报告了八种不同药物类型中使用的每种赋形剂类别和赋形剂化学品的流行情况，包括单克隆抗体、抗体缀合物、细胞因子和生长因子、酶、多肽激素、肺表面活性剂、重组融合蛋白和毒素。我们还报告了所有治疗性蛋白质中赋形剂类型的流行情况，以及每种药物推荐的 pH 范围、赋形剂浓度范围和给药途径。

 结论

我们的分析结果表明某些赋形剂是单克隆抗体、细胞因子和多肽激素所共有的。我们还报告蛋白质药物产品特有的赋形剂，例如氨基酸、增溶剂和冻干保护剂。总体而言，我们的报告总结了市售生物技术衍生的治疗性生物制品中使用的赋形剂的现状。