Novartis Institutes for BioMedical Research, 700 Main Street, Cambridge, MA 02139, USA.
Radius Health, Inc, 550 E. Swedesford Road, Suite 370, Wayne, PA 19087, USA.
Adv Drug Deliv Rev. 2020 Dec;167:66-77. doi: 10.1016/j.addr.2020.05.009. Epub 2020 May 27.
Despite the increasing trend towards subcutaneous delivery of monoclonal antibodies, factors influencing the subcutaneous bioavailability of these molecules remain poorly understood. To address critical knowledge gaps and issues during development of subcutaneous dosage forms for monoclonal antibodies, the Subcutaneous Drug Delivery and Development Consortium was convened in 2018 as a pre-competitive collaboration of recognized industry experts. One of the Consortium's eight problem statements highlights the challenges of predicting human bioavailability of subcutaneously administered monoclonal antibodies due to a lack of reliable in vitro and preclinical in vivo predictive models. In this paper, we assess the current landscape in subcutaneous bioavailability prediction for monoclonal antibodies and discuss the gaps and opportunities associated with bioavailability models for biotherapeutics. We also issue an open challenge to industry and academia, encouraging the development of reliable models to enable subcutaneous bioavailability prediction of therapeutic large molecules in humans and improve translation from preclinical species.
尽管单克隆抗体的皮下给药呈上升趋势，但影响这些分子皮下生物利用度的因素仍知之甚少。为了解决单克隆抗体皮下给药剂型开发过程中的关键知识空白和问题，皮下药物递送和开发联盟于 2018 年成立，作为公认的行业专家的预竞争合作。联盟的八个问题陈述之一强调了由于缺乏可靠的体外和临床前体内预测模型，预测皮下给予的单克隆抗体的人体生物利用度的挑战。在本文中，我们评估了单克隆抗体皮下生物利用度预测的当前现状，并讨论了与生物治疗药物生物利用度模型相关的差距和机遇。我们还向工业界和学术界提出了一个公开挑战，鼓励开发可靠的模型，以实现对人类治疗性大分子量药物的皮下生物利用度预测，并提高从临床前物种的转化。
