Development and Production of Anti-Malarial Biologicals

疟疾单抗CIS43LS是在VRC发现并提供给疫苗生产规划实验室（VPP）的。VPP对该单抗进行了可制造性评估，并确定该单抗适合最终的GMP生产。将VRC抗体引入人体临床试验的下一步涉及使用现行的良好生产规范（cGMP）生产大量单抗。VPP负责cGMP的生产和VRC单克隆抗体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。VPP扩展了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并签订合同，以增加生物制剂制造的能力。VPP开发了生产疟疾单抗所需的生产工艺、最终配方缓冲液和分析方法，并将该工艺移交给VCMP进行cGMP生产和产品释放/稳定性测试。在收到美国FDA关于首次人体临床试验的安全通知之前，FDA对产品的适用性有疑问，VPP解决了FDA的满意度。

Malaria mAb CIS43LS was discovered at the VRC and provided to the Vaccine Production Program Laboratory (VPP). The VPP conducted a manufacturability assessment of the mAb and determined the mAb was suitable for eventual GMP production. The next step in bringing the VRC antibody to human clinical testing involves producing large quantities of the mAb using current Good Manufacturing Practices (cGMP). 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 malaria mAb, transferred the process to the VCMP for cGMP production and product release/stability testing. Prior to receiving a Safe-to-proceed notification from the US FDA for the first-in-human clinical trial, the FDA had questions about the suitability of the product which the VPP addressed to the FDAs satisfaction. 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 is developing a second anti-malaria mAb, L9LS. Following a manufacturability analysis, the VPP generated stable, clonal cell lines, selected the optimum clone, and transferred the cell bank to the VCMP for cGMP Master Cell Bank production. In parallel, L9LS-specific processes for large-scale cell culture and mAb purification were developed. 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 will allow for clinical dosing and routes of administration that would not have been possible at lower mAb Drug Product concentrations. Transfer of the manufacturing, analytical, and formulation processes to cGMP manufacturing is in progress.