Development and Production of Anti-Malarial Biologicals

抗疟生物制剂的开发与生产

• 批准号: 10268823
• 负责人: Jason Gall
• 金额: $ 107.72万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10268823
• 关键词: Address; Antibodies; Antimalarials; Biological; Biotechnology; Buffers; Cell Culture Techniques; Cell Line; Clinical; Clinical Trials; Clone Cells; Contracts; Development; Documentation; Dose; Formulation; Human; Industry; Infection prevention; Investigational New Drug Application; Laboratories; Malaria; Methods; Monoclonal Antibodies; Notification; Phase; Plants; Process; Production; Research; Route; Testing; Therapeutic Monoclonal Antibodies; Toxicology; Vaccine Production; Vaccines; analytical method; assay development; cell bank; clinical application; clinical material; first-in-human; improved; manufacturability; manufacturing process; programs; research clinical testing; satisfaction; stability testing; vaccine development

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.

疟疾单克隆抗体 CIS43LS 在 VRC 发现并提供给疫苗生产计划实验室 (VPP)。 VPP 对 mAb 进行了可制造性评估，并确定该 mAb 适合最终的 GMP 生产。将 VRC 抗体引入人体临床测试的下一步涉及使用现行良好生产规范 (cGMP) 生产大量 mAb。 VPP 负责 cGMP 生产以及监管部门提交 VRC 单克隆抗体临床试验所需的制造文件。为了迅速满足其临床试验计划的关键计划需求，VRC 开发了一个疫苗中试工厂，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，将单克隆抗体的生产纳入其中。 VPP 还与疫苗/生物技术行业的公司建立合作伙伴关系并签订合同，以提高生物制品制造的能力和能力。 VPP 开发了生产疟疾单克隆抗体所需的生产工艺、最终配方缓冲液和分析方法，并将该工艺转移至 VCMP 进行 cGMP 生产和产品放行/稳定性测试。在收到美国 FDA 发出的首次人体临床试验安全进行通知之前，FDA 对产品的适用性存在疑问，VPP 向 FDA 提出了满意的答复。 对这些生物制品的需求不断增加，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 正在开发第二种抗疟疾单克隆抗体 L9LS。经过可制造性分析后，VPP 生成稳定的克隆细胞系，选择最佳克隆，并将细胞库转移至 VCMP 进行 cGMP 主细胞库生产。与此同时，还开发了用于大规模细胞培养和 mAb 纯化的 L9LS 特定工艺。 VPP 发现该 mAb 在某些缓冲液配方中高度稳定，使得 VPP 将 L9LS 的浓度比大多数 mAb 高 50%。这将允许在较低的单克隆抗体药品浓度下不可能实现的临床剂量和给药途径。制造、分析和配方流程正在向 cGMP 制造转移。