Production of a Broadly Neutralizing HIV Antibodies

VRC的疫苗生产项目实验室（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。VPPL扩大了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开发生产mAb所需的生产工艺和分析方法，将工艺转移至VCMP进行cGMP生产和产品放行/稳定性检测。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埃博拉治疗性抗体mAb 114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年扎伊尔埃博拉疫情的随机对照试验中进行研究，导致FDA完全批准Ridgeback Biotherapeutics生物制剂许可证申请。已经开发了许多具有商业利益的mAb（参见下文的产品或服务）。随着我们沿着开发路线前进，对这些分子的需求增加，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已生产了82.5 kg VRC 01用于临床试验（I期研究和AMP II期研究）和mAb 10 E8 VLS、N6 LS、CAP 256 LS、VRC 01 LS和VRC 07 - 523 LS的I期生产批次。 此外，VPP还生产了下一代HIV-1 mAb VRC 01 v23 LS和VRC01.23 LS的主细胞库，沿着完成了PGDM 1400 LS的制剂灌装，以支持DAIDS。

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.