The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Janssen, A Division of Johnson & Johnson Pte Ltd., Singapore, Singapore.
Adv Ther. 2021 May;38(5):2077-2093. doi: 10.1007/s12325-021-01688-9. Epub 2021 Mar 21.
In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality.
在美国，互替性指定为生物类似药赞助商提供了一条途径，使其能够实现小分子仿制药的标准：药房级别的创新药物自动替代。没有其他主要的卫生当局将互替性与自动替代联系起来，因为所有当局都要求处方者或患者参与药物更换。这篇社论考虑了自动替代的临床影响和实用性。首先，互替性与非医疗性转换（NMS）有关，即在病情稳定的患者中出于非临床原因转换治疗的做法。NMS 可能会引起不愿意或不愿意转换的人的负面情绪，从而对治疗结果产生不利影响（即，反安慰剂效应）。事实上，在肿瘤坏死因子抑制剂的真实世界研究中，由于非医疗原因转换为生物类似药的患者的停药率比维持使用创新药物的历史队列更高。其次，互替性可能会阻碍药物警戒和可追溯性，因为并非所有司法管辖区都要求创新药物和生物类似药具有不同的生物名称。第三，美国食品和药物管理局的互替性指定仅允许生物类似药自动替代其创新药物，而不能替代其他生物类似药（如果有）。需要对药剂师进行教育，以避免在同一创新药物的生物类似药之间进行未经批准的自动替代。最后，根据当前美国联邦法律，一旦获得互替性指定，它将永久存在。然而，创新药物和生物类似药的供应链是独立维持的，不需要重新确认生物相似性或互替性。我们认为，需要更多的指导，以使生物类似药和创新药物的自动替代成为现实。
