Development and Production of Anti-Malarial Biologicals

抗疟生物制剂的开发与生产

• 批准号: 10930570
• 负责人: Jason Gall
• 金额: $ 11.22万
• 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/10930570
• 关键词: Antibodies; Antimalarials; Biotechnology; Buffers; COVID-19 pandemic; Clinical; Clinical Trials; Contracts; Development; Documentation; Dose; Enrollment; Formulation; Human; Industry; Infection prevention; Investigational New Drug Application; Kenya; Laboratories; Malaria; Malaria prevention; Mali; Methods; Monoclonal Antibodies; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Plants; Process; Production; Research; Route; Therapeutic Monoclonal Antibodies; Toxicology; Vaccine Production; Vaccines; analytical method; assay development; cGMP production; cell bank; clinical application; clinical material; improved; malaria infection; manufacture; manufacturing process; manufacturing test; phase 1 study; phase 2 study; programs; stability testing; vaccine development

Malaria mAb CIS43LS was discovered at the VRC and provided to the Vaccine Production Program Laboratory (VPP). 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 CIS43LS, transferred the process to the VCMP for cGMP production and product release/stability testing. The VRC received safe-to-proceed in November 2019 and initiated Phase I clinical trials. Due to the COVID-19 pandemic, the controlled-human malaria infection part of the Phase I was delayed until October 2020. Additionally, in May of 2021 a Phase II clinical trial was initiated for CIS43LS in Mali for the prevention of malaria infection. Enrollment completed in August of 2021 with topline results from this trial provided in March of 2022. 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 developed a second anti-malaria mAb, L9LS, leading to the production of a master cell bank, drug substance, drug product and the filing of an IND in August 2021. During development, The VPP discovered that the mAb was highly stable in certain buffer formulations, allowing for the VPP to concentrate L9LS 50% higher than most mAbs. This allows for clinical dosing and routes of administration that would not have been possible at lower mAb Drug Product concentrations. The IND for L9LS received safe-to-proceed September 9, 2021 and proceed in October for the initial Phase I study with controlled-human challenge October 26th. In 2022, a Phase II study was initiated in Mali and a second one is anticipated to start in Kenya.

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 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 开发了制造 CIS43LS 所需的制造工艺、最终配方缓冲液和分析方法，并将该工艺转移到 VCMP 进行 cGMP 生产和产品放行/稳定性测试。 VRC 于 2019 年 11 月获得安全进展并启动 I 期临床试验。由于COVID-19大流行，第一阶段的受控人类疟疾感染部分被推迟到2020年10月。此外，2021年5月在马里启动了CIS43LS的第二阶段临床试验，用于预防疟疾感染。招募于 2021 年 8 月完成，该试验的主要结果于 2022 年 3 月提供。 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 开发了第二种抗疟疾单克隆抗体 L9LS，从而生产了主细胞库、原料药、药品，并于 2021 年 8 月提交了 IND。在开发过程中，VPP 发现该单克隆抗体在某些缓冲液配方，使 VPP 的 L9LS 浓度比大多数 mAb 高 50%。这使得临床剂量和给药途径在较低的单克隆抗体药品浓度下是不可能的。 L9LS 的 IND 于 2021 年 9 月 9 日收到，可以安全进行，并于 10 月继续进行初始 I 期研究，并于 10 月 26 日进行受控人体挑战。 2022 年，第二阶段研究在马里启动，第二阶段研究预计将在肯尼亚启动。