Brookes Roger H, Hakimi Jalil, Ha Yukyung, Aboutorabian Sepideh, Ausar Salvador F, Hasija Manvi, Smith Steven G, Todryk Stephen M, Dockrell Hazel M, Rahman Nausheen
Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
Faculty of Infectious and Tropical Diseases; Department of Immunology and Infection; London School of Hygiene and Tropical Medicine; London, UK.
Hum Vaccin Immunother. 2014;10(4):1129-35. doi: 10.4161/hv.27657. Epub 2014 Jan 8.
Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.
了解任何用于人类的药物制剂的相关生物活性至关重要。对于基于疫苗的制剂，活性必须反映预期的免疫反应，而对于非疫苗治疗剂，如单克隆抗体，则希望制剂不会引发免疫反应。在制剂早期研发过程中，可以通过高通量筛选（HTS）方式监测各种生化和生物物理特性。然而，在动物模型中以这种方式筛选样品的免疫功能仍然不切实际，而且可以说是不道德的。此外，免疫功能的数据比制剂设计滞后数月，难以实时关联到制剂。动物试验也可能无法准确反映人类的反应。为了进行更有效的制剂筛选，可以采用人全血（hWB）方法来评估免疫功能。功能活性直接关系到人类对完整制剂（佐剂/抗原）的免疫反应，包括佐剂反应、抗原反应、佐剂调节的抗原反应、稳定性以及潜在的安全性。以下评论将讨论hWB方法作为一种有价值的新工具，用于降低生产、制剂设计和临床进展中的风险。
