Development and Production of Anti-Malarial Biologicals

疟疾单抗Cis43LS是在VRC发现的，并提供给疫苗生产计划实验室(VPP)。VPP对该单抗进行了可制造性评估，并确定该单抗适合最终生产GMP。将VRC抗体引入人体临床测试的下一步涉及使用当前的良好制造规范(CGMP)生产大量mAb。VPP负责cGMP的生产和监管提交用于临床试验的VRC单抗所需的制造文件。为了迅速满足其临床试验计划的关键计划需求，VRC开发了一个疫苗试点工厂，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，包括制造克隆抗体。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，以增加生物制品制造的能力和能力。VPP制定了制造疟疾单抗所需的制造工艺、最终配方缓冲和分析方法，并将该工艺移交给VCMP用于cGMP生产和产品释放/稳定性测试。在收到来自美国FDA的首例人体临床试验的安全进行通知之前，FDA对VPP提出的该产品的适宜性提出了质疑，以使FDAS满意。 对这些生物制品的需求增加了，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正在开发第二种抗疟疾单抗L9LS。在可制造性分析之后，VPP产生了稳定的克隆细胞系，选择了最佳克隆，并将细胞库转移到VCMP用于生产cGMP主细胞库。同时，开发了大规模细胞培养和单抗纯化的L9LS特异性工艺。VPP发现，单抗在某些缓冲配方中高度稳定，允许VPP将L9LS浓缩到比大多数单抗高50%的水平。这将允许临床剂量和给药途径，这在较低的mAb药物产品浓度下是不可能的。将制造、分析和配方工艺转移到cGMP制造正在进行中。

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.