Production of a Broadly Neutralizing HIV Antibodies

VRC的疫苗生产规划实验室（VPP）负责cGMP的生产和VRC单克隆抗体提交临床试验所需的生产文件。为了迅速满足其临床试验项目的关键项目需求，VRC开发了一个疫苗试验工厂，称为VCMP（疫苗临床材料项目），用于生产I/II/III期试验的临床材料。VPPL扩展了VCMP生产单克隆抗体的能力。VPPL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。VPPL开发制造单克隆抗体所需的制造工艺和分析方法，将该工艺转移到VCMP进行cGMP生产和产品释放/稳定性测试。这种方法使VRC能够快速应对新出现的公共卫生威胁，正如VRC的埃博拉治疗性抗体mAb114所证明的那样，该抗体在同情使用协议下使用，并在刚果民主共和国2018/19埃博拉扎伊尔疫情中进行了随机对照试验，导致FDA完全批准了Ridgeback生物疗法生物制剂许可证申请。治疗埃博拉病毒。已经开发了许多具有商业利益的单克隆抗体（见下文的产品或服务）。随着开发的深入，对这些分子的需求也在增加，这就要求开发团队进一步改进制造工艺和测试方法，以满足需求。VPP已经生产了82.5公斤VRC01用于临床试验（1期研究和AMP 2期研究）和单抗10E8VLS、N6LS、CAP256LS、VRC01LS和VRC07-523LS的1期生产批次。此外，VPP还为新一代HIV-1单克隆抗体VRC01v23LS和VRC01.23LS生产了主细胞库，并完成了PGDM1400LS的药物填充，以支持艾滋病。

Vaccine Production Program Laboratory (VPP) at the VRC 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 VPPL expanded the capability of the VCMP for the manufacture of monoclonal antibodies. The VPPL also engages in partnerships and contracts with companies in the vaccine/biotech industry for additional capacity and capability in biologicals manufacturing. The VPPL develops the manufacturing process and analytical methods needed for manufacturing mAbs, transfers the process to the VCMP for cGMP production and product release/stability testing. Such an approach enables the VRC to rapidly respond to emerging public health threats, as evidenced by the VRCs Ebola therapeutic antibody, mAb114, that was used under compassionate use protocols and studied under randomized control trials in the 2018/19 Ebola Zaire outbreak in the Democratic Republic of the Congo leading to the full FDA approval of Ridgeback Biotherapeutics Biologics License Application. for treatment of Ebola.A number of mAbs have been developed that have commercial interest (see Products or Services, below). As we proceed down the development pathway the demand for these molecules has increased requiring the development groups to further improve the manufacturing process and test methods to keep up with demand. The VPP has produced 82.5 kg of VRC01 for clinical trial use (Phase 1 studies and the AMP Phase 2 study) and Phase 1 production lots of the mAbs 10E8VLS, N6LS, CAP256LS, VRC01LS, and VRC07-523LS. Additionally, the VPP has produced master cell banks for next-gen HIV-1 mAbs VRC01v23LS and VRC01.23LS, along with completed a drug product fill of PGDM1400LS to support DAIDS.