a Sanofi, Translational Medicine & Clinical Pharmacology , Cambridge , MA , USA.
b Sanofi, Translational Medicine & Clinical Pharmacology , 55 Corporate Drive, Bridgewater , NJ , USA.
MAbs. 2018 Jan;10(1):18-33. doi: 10.1080/19420862.2017.1392424. Epub 2017 Nov 7.
The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.
注射型药物-器械组合（DDC）产品的开发是一个复杂且不断发展的过程，需要大量的时间和资金投入。因此，在关键性试验开始时，商业制剂（或剂型）通常还未准备就绪，在临床开发过程中经常会对药物产品进行变更（生产工艺或剂型）。为了安全地将这些变更引入临床，需要采用科学合理且稳健的桥接策略。目前尚无单一的开发模式，但基于风险的分层方法已被广泛接受。桥接方案所需的严格程度取决于变更相关的风险水平。只有在晚期发生重要变更时，才需要进行临床药代动力学/药效学可比性或结局研究。此外，注射型 DDC 需要以用户为中心，可能需要在实际临床环境中进行可用性评估，以支持 DDC 的批准。在本文中，我们讨论了注射型 DDC 在生产工艺和剂型开发过程中的常见问题，并探讨了在建立临床策略以解决这些问题时的实际考虑因素，包括临床研究的关键要素。我们还分析了行业中的当前实践，并审查了 DDC 领域的相关监管指南的现状。
