Amgen Inc., Thousand Oaks, CA, USA,
BioDrugs. 2014 Aug;28(4):363-72. doi: 10.1007/s40259-014-0088-z.
Biological medicines (biologics) are produced in living cells and purified in complex, multi-step processes. Compared with chemically synthesized small-molecule drugs, biologics are more sensitive to changes in manufacturing conditions. Process and product consistency should be founded on rigorous design and control of manufacturing processes, but consistency is ultimately ensured through robust quality systems. Even a minor change in any component of a quality system could lead to product drift, evolution, and divergence, which may impact the quality, safety, efficacy, and/or interchangeability of biologics. Unintended or unexplained deviations in manufacturing processes can lead to excursions in product attributes (i.e., drift). Well-managed quality systems can help detect and mitigate drift. Occasionally, quality attributes could shift outside of established acceptable ranges as the result of a known manufacturing change (defined here as evolution). Such changes should be studied extensively for effects on product safety and efficacy. With the advent of biosimilars, similar biologics will be produced by multiple manufacturers with different quality systems. Different patterns of product drift and evolution could contribute, over time, to clinically meaningful differences among biologics, including among originator products across regions and among originator products and biosimilar products, a process defined here as divergence. Manufacturers and policymakers can minimize the potential impact of divergence by establishing robust pharmacovigilance systems; requiring distinguishable names for all biologics, including both originator products and biosimilars; adhering to high standards for designations of interchangeability; and ensuring that patient medical records accurately reflect the specific biologic dispensed, especially if the biologic could be sourced from multiple manufacturers.
生物制药（biologics）是在活细胞中生产的，并通过复杂的多步骤过程进行纯化。与化学合成的小分子药物相比，生物制药对制造条件的变化更为敏感。工艺和产品的一致性应建立在严格设计和控制制造工艺的基础上，但一致性最终是通过强大的质量体系来保证的。质量体系的任何组成部分的微小变化都可能导致产品漂移、演变和发散，从而影响生物制药的质量、安全性、疗效和/或可互换性。制造过程中未预期或无法解释的偏差可能导致产品属性的偏移（即漂移）。管理良好的质量体系有助于检测和减轻漂移。偶尔，由于已知的制造变化（此处定义为演变），质量属性可能会超出既定可接受范围。应对此类变化进行广泛研究，以评估其对产品安全性和疗效的影响。随着生物类似药的出现，多个制造商将使用不同的质量体系生产类似的生物制药。随着时间的推移，不同的产品漂移和演变模式可能会导致生物制药之间出现临床意义上的差异，包括不同地区的原创产品之间以及原创产品和生物类似产品之间的差异，这里定义为发散。制造商和政策制定者可以通过建立强大的药物警戒系统、要求所有生物制药（包括原创产品和生物类似产品）具有可区分的名称、遵守可互换性指定的高标准以及确保患者病历准确反映所配给的特定生物制药（特别是如果该生物制药可由多个制造商提供），来最大程度地减少发散的潜在影响。
