Guttieres Donovan, Sinskey Anthony J, Springs Stacy L
Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Antib Ther. 2021 Mar 20;4(1):60-71. doi: 10.1093/abt/tbab006. eCollection 2021 Jan.
Neutralizing antibodies (nAbs) against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) can play an important role in reducing impacts of the COVID-19 pandemic, complementing ongoing public health efforts such as diagnostics and vaccination. Rapidly designing, manufacturing and distributing nAbs requires significant planning across the product value chain and an understanding of the opportunities, challenges and risks throughout.
A systems framework comprised of four critical components is presented to aid in developing effective end-to-end nAbs strategies in the context of a pandemic: (1) product design and optimization, (2) epidemiology, (3) demand and (4) supply. Quantitative models are used to estimate product demand using available epidemiological data, simulate biomanufacturing operations from typical bioprocess parameters and calculate antibody production costs to meet clinical needs under various realistic scenarios.
In a US-based case study during the 9-month period from March 15 to December 15, 2020, the projected number of SARS-CoV-2 infections was 15.73 million. The estimated product volume needed to meet therapeutic demand for the maximum number of clinically eligible patients ranged between 6.3 and 31.5 tons for 0.5 and 2.5 g dose sizes, respectively. The relative production scale and cost needed to meet demand are calculated for different centralized and distributed manufacturing scenarios.
Meeting demand for anti-SARS-CoV-2 nAbs requires significant manufacturing capacity and planning for appropriate administration in clinical settings. MIT Center for Biomedical Innovation's data-driven tools presented can help inform time-critical decisions by providing insight into important operational and policy considerations for making nAbs broadly accessible, while considering time and resource constraints.
针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的中和抗体（nAbs）在减轻新冠疫情影响方面可发挥重要作用，对正在进行的诊断和疫苗接种等公共卫生工作起到补充作用。快速设计、生产和分发中和抗体需要在整个产品价值链上进行大量规划，并了解其中存在的机遇、挑战和风险。
本文提出了一个由四个关键部分组成的系统框架，以帮助在疫情背景下制定有效的端到端中和抗体策略：（1）产品设计与优化，（2）流行病学，（3）需求，（4）供应。使用定量模型，利用现有的流行病学数据估计产品需求，根据典型生物工艺参数模拟生物制造操作，并计算在各种现实情况下满足临床需求的抗体生产成本。
在2020年3月15日至12月15日这9个月期间以美国为基础的案例研究中，预计SARS-CoV-2感染人数为1573万。对于0.5克和2.5克剂量规格，满足最大数量临床合格患者治疗需求所需的估计产品量分别在6.3吨至31.5吨之间。针对不同的集中式和分布式制造场景，计算了满足需求所需的相对生产规模和成本。
满足抗SARS-CoV-2中和抗体的需求需要大量的制造能力，并需要对临床环境中的适当给药进行规划。麻省理工学院生物医学创新中心提出的数据驱动工具，可通过深入了解使中和抗体广泛可用的重要操作和政策考虑因素，同时考虑时间和资源限制，来帮助做出关键决策。
