Biologic excipients: Importance of clinical awareness of inactive ingredients
Biologic excipients: Importance of clinical awareness of inactive ingredients
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DOI：
10.1371/journal.pone.0235076
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发表时间：
2020-06-25
期刊：
影响因子：
3.7
通讯作者：
Wilson, Leslie
中科院分区：
文献类型：
--
作者：
Ionova, Yelena;Wilson, Leslie
由于生物药品的复杂性和脆弱性，在其制剂开发中存在一些挑战。添加辅料是为了增加产品的稳定性，保持强直性，并促进给药。这些添加剂的潜在影响值得临床考虑。我们通过一个评估框架，根据赋形剂的类型和可变性评估了赋形剂的安全风险，该评估框架量化了230种生物制剂中赋形剂的复杂性，并通过发表的病例报告确定了赋形剂相关的不良事件。一种生物制剂平均含有4.45种辅料，是口服药物的一半。频率分布严重倾向于最常见的辅料：水（40.4%）、氯化钠（38.3%）、聚山梨酯80（28.7%）、蔗糖（24.4%）和甘露醇（20.9%），44.4%的配方没有列出最常见的非活性成分的浓度。一项文献检索显示，只有17例与赋形剂相关的不良事件报告，这表明临床医生需要更加明确化学添加剂的安全性。这些病例包括注射部位反应、过敏反应、高血糖和急性肾功能衰竭。随着生物制药市场的扩大，考虑生物辅料的安全性数据是很重要的，这样可以针对特定的患者进行适当的治疗。
Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.