Regulatory Affairs, Chemistry, Manufacturing and Controls, Novo Nordisk A/S, Søborg, Denmark.
Regulatory Affairs, Device, Novo Nordisk A/S, Søborg, Denmark.
AAPS J. 2024 Sep 4;26(5):100. doi: 10.1208/s12248-024-00968-w.
The development of new large molecule drug therapies along with the innovation of biologic-device combination products such as prefilled syringes, autoinjectors and pen injectors have significantly impacted the treatment of new diseases and has improved the process of administering parenteral medicines. To support the regulatory approval of a new biologic-device combination products or subsequent chemistry, manufacturing and control changes impacting a combination product, sponsor companies must thoroughly assess the potential impact to product quality, safety and efficacy. In this report, a risk-based process to determine the potential impact to product quality, safety, and efficacy as well as corresponding regulatory actions supporting a chemistry, manufacturing and control change is presented. The risk assessment includes the standardized assessment of a) chemistry, manufacturing and control risk factors, potential responses and appropriately weighted scoring; b) pharmacokinetic risk factors, potential responses and appropriately weighted scoring; and c) the use of a 2-dimensional risk grid to combine the chemistry, manufacturing and control risks and pharmacokinetic risks to provide a regulatory recommendation. Three case studies (two clinical case studies and a post-approval case study) are provided to demonstrate the assessment process and capabilities.
新型大分子药物疗法的发展以及预填充注射器、自动注射器和笔式注射器等生物器械组合产品的创新，显著影响了新疾病的治疗，并改进了肠外药物给药流程。为支持新型生物器械组合产品的监管批准或后续对组合产品产生影响的化学、制造和控制变更，申办方公司必须彻底评估对产品质量、安全性和疗效的潜在影响。在本报告中，介绍了一种基于风险的方法来确定对产品质量、安全性和疗效的潜在影响，以及支持化学、制造和控制变更的相应监管措施。风险评估包括标准化评估：a）化学、制造和控制风险因素、潜在应对措施和适当加权评分；b）药代动力学风险因素、潜在应对措施和适当加权评分；以及 c）使用二维风险网格将化学、制造和控制风险与药代动力学风险相结合，提供监管建议。提供了三个案例研究（两个临床案例研究和一个批准后案例研究）来演示评估过程和能力。
