Development and Production of Anti-Malarial Biologicals

疟疾mAb CIS 43 LS是在VRC发现的，并提供给疫苗生产计划实验室（VPP）。 VPP负责cGMP生产和临床试验用VRC mAb监管提交所需的生产文件。为了迅速满足其临床试验计划的关键计划需求，VRC开发了一个疫苗试验工厂，称为VCMP（疫苗临床材料计划），用于生产I/II/III期试验的临床材料。VPP扩大了VCMP的能力，包括单克隆抗体的生产。VPP还与疫苗/生物技术行业的公司建立伙伴关系和签订合同，以增加生物制剂制造的能力。VPP开发了生产CIS 43 LS所需的生产工艺、最终制剂缓冲液和分析方法，并将该工艺转移至VCMP进行cGMP生产和产品放行/稳定性检测。VRC于2019年11月获得安全进行，并启动了I期临床试验。 由于COVID-19疫情，第一阶段的人类疟疾感染控制部分延迟至二零二零年十月。 此外，2021年5月，在马里启动了CIS 43 LS预防疟疾感染的II期临床试验。 入组于2021年8月完成，预计试验结果将于2022年初公布。 对这些生物制剂的需求增加，要求开发小组进一步改进制造工艺和测试方法，以跟上需求。VPP开发了第二种抗疟疾mAb L9 LS，导致主细胞库、原料药、药品的生产，并于2021年8月提交IND。在开发过程中，VPP发现mAb在某些缓冲液制剂中高度稳定，使VPP能够将L9 LS浓缩至比大多数mAb高50%。这使得临床给药和给药途径在较低的mAb制剂浓度下是不可能的。FDA正在对IND进行审查，以便在2021年9月开始临床试验。

Malaria mAb CIS43LS was discovered at the VRC and provided to the Vaccine Production Program Laboratory (VPP). The VPP is responsible for cGMP production and the manufacturing documentation needed for regulatory submission of VRC mAbs for clinical trials. To expeditiously meet the critical program needs of its Clinical Trials Program, the VRC developed a vaccine pilot plant, known as the VCMP (Vaccine Clinical Materials Program) for the manufacture of clinical materials for Phase I/II/III trials. The VPP expanded the capability of the VCMP to include the manufacture of monoclonal antibodies. The VPP also engages in partnerships and contracts with companies in the vaccine/biotech industry for additional capacity and capability in biologicals manufacturing. The VPP developed the manufacturing process, final formulation buffer, and analytical methods needed for manufacturing the CIS43LS, transferred the process to the VCMP for cGMP production and product release/stability testing. The VRC received safe-to-proceed in November 2019 and initiated Phase I clinical trials. Due to the COVID-19 pandemic, the controlled-human malaria infection part of the Phase I was delayed until October 2020. Additionally, in May of 2021 a Phase II clinical trial was initiated for CIS43LS in Mali for the prevention of malaria infection. Enrollment completed in August of 2021 with results from the trial expected in early 2022. The demand for these biologicals has increased, requiring the development groups to further improve the manufacturing process and test methods to keep up with demand. The VPP developed a second anti-malaria mAb, L9LS, leading to the production of a master cell bank, drug substance, drug product and the filing of an IND in August 2021. During development, The VPP discovered that the mAb was highly stable in certain buffer formulations, allowing for the VPP to concentrate L9LS to 50% higher than most mAbs. This allows for clinical dosing and routes of administration that would not have been possible at lower mAb Drug Product concentrations. FDA review of the IND is in-progress, to enable a clinical trial start in September 2021.