Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
Biotechnol Bioeng. 2021 Nov;118(11):4186-4203. doi: 10.1002/bit.27905. Epub 2021 Aug 5.
There is a strong and growing interest in the development and production of gene therapy products, including those utilizing adeno-associated virus (AAV) particles. This is evident with the increase in the number of clinical trials and agency approvals for AAV therapeutics. As bioproduction of AAV viral vectors matures, a quality by design (QbD) approach to process development can aid in process robustness and product quality. Furthermore, it may become a regulatory expectation. The first step in any QbD approach is to determine what physical, chemical, biological, or microbiological property or characteristic product attributes should be controlled within an appropriate limit, range, or distribution to ensure the desired product quality. Then predefined goals are set to allow proactive process development to design in quality. This review lists typical quality attributes used for release testing of AAV viral vectors and discusses these and selected attributes important to extended characterization studies in terms of safety, efficacy, and impact upon the patient immune response.
人们对基因治疗产品的开发和生产越来越感兴趣，包括利用腺相关病毒（AAV）颗粒的产品。随着利用 AAV 治疗的临床试验和机构批准数量的增加，这一点变得明显。随着 AAV 病毒载体的生物生产逐渐成熟，采用质量源于设计（QbD）方法进行工艺开发有助于提高工艺稳健性和产品质量。此外，这可能成为监管期望。QbD 方法的第一步是确定应在适当的限制、范围或分布内控制哪些物理、化学、生物学或微生物学特性或产品属性，以确保所需的产品质量。然后设定预定目标，以允许主动进行工艺开发，在设计中融入质量。本综述列出了用于 AAV 病毒载体放行检测的典型质量属性，并讨论了这些属性以及对安全性、疗效以及对患者免疫反应影响的选定属性在扩展特性研究中的重要性。
