BIOLOGICS SUBJECT MATTER EXPERT (SME) CONSULTING SERVICES

生物制品主题专家 (SME) 咨询服务

• 批准号: 10788054
• 负责人: SUSAN BENJAMIN
• 金额: $ 22.08万
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2023-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10788054
• 关键词: Address; Antibodies; Antisense Oligonucleotides; Area; Biochemistry; Biological; Biological Assay; Biological Process; Biological Products; Biological Response Modifier Therapy; Cell Therapy; Cells; Chemistry; Clinical; Clinical Research; Collaborations; Complex; Contractor; Contracts; Data; Data Analyses; Development; Development Plans; Electronic Mail; Evaluation Studies; Feedback; Formulation; Government; Guidelines; In Vitro; Investigational Drugs; Investigational New Drug Application; Label; Leadership; Lentivirus; Liposomes; Logistics; Methodology; Methods; Modality; Needs Assessment; Oligonucleotides; Peptides; Performance; Persons; Pharmacology; Pharmacology Study; Pharmacology and Toxicology; Polymers; Preparation; Principal Investigator; Process; Protocols documentation; Published Comment; Rare Diseases; Recombinant Proteins; Recommendation; Regulation; Regulatory Affairs; Reporting; Resources; Risk; Role; Running; Services; Small Interfering RNA; Specific qualifier value; Strategic Planning; Telephone; Testing; Therapeutic; Toxicology; United States National Institutes of Health; Viral; Viral Vector; Visit; Work; analytical method; design; evaluation/testing; improved; in silico; in vivo Model; lead optimization; manufacture; meetings; member; method development; model development; nanoparticle; nervous system disorder; operation; pharmacokinetics and pharmacodynamics; pre-clinical; preclinical evaluation; programs; protein purification; research and development; research clinical testing; safety study; safety testing; scale up; screening; symposium; therapeutic development; timeline

The consultants will be expected to provide feedback and guidance on scientific processes and gap areas/needs assessments through in-person meetings, conference calls, and email. The consultants will also be required to provide information on the ultra-rare disease space, preferably with a focus on neurological disorders. This will assist the NIH with better understanding the requirements for product developers to move their therapeutics through the research and development stage into clinical evaluation studies as well as development strategies and alternatives. Specific consulting responsibilities will depend on the expertise of the consultants and the needs of the program. Performance Area 1: Biologics Chemistry, Manufacturing and Controls (CMC) SME(s) Subject matter experts in manufacturing of the various biological therapeutics platforms, including but not limited to, modalities such as therapeutic oligonucleotides (e.g., antisense oligonucleotide -ASOs, small interfering RNAs -siRNAs, etc.), AAV, lentivirus or other viral vector therapeutics, purified proteins, recombinant proteins, peptides, antibody-based and cell-based therapeutics, and ex vivo cellular therapies are required. Biologics CMC consultants will be expected to provide senior-level chemistry, manufacturing and controls expertise and contribute feedback and guidance on projects to the NIH and to LDT members through conference calls and by email. Please note that, for Performance Area 1, the Government will consider SME consultants with expertise in one or more manufacturing modalities. The role of the CMC SME consultant may include, but is not limited to, the following responsibilities and tasks: a) Review and comment on the adequacy of biologic manufacturing, including scale-up, analytical method development, and process development (upstream and downstream processing) approaches proposed by Principal Investigators (PIs) and CMOs b) Provide guidance on delivery methods, which may include complex formulations such as polymer, liposomes, and other nanoparticle constructs c) Provide expert advice on master and working cell and viral bank development and testing d) Provide strategy and feedback on biologics process development and manufacturing plans proposed by the team e) Provide feedback on therapeutic oligonucleotide sequences and synthesis processes proposed by the team f) Provide feedback on proposed biologics formulations g) Provide feedback on critical quality attributes, release testing, etc. h) Evaluate CMC data on a weekly or biweekly basis i) Serve as the CMC expert in order to identify potential product manufacturing challenges and suggest strategies to address these challenges j) Accompany NIH staff or visit, at NIH staff request, CROs and CMOs under contract to the NIH. k) Inspect facilities and discuss appropriateness of CRO/CMO proposed methodology l) CMC consultant may be asked to evaluate the potential tractability (including surrounding IP space) of a proposed biological therapeutic m) Collaborate on design of investigative studies in support of therapeutics development projects n) In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage CMC to facilitate preclinical evaluation and safety testing, Investigational New Drug (IND) submissions, and clinical studies o) Facilitate LDT discussions via telephone and email regarding assigned CMC efforts p) Provide strategic guidance for the continued development and improvement of the BPN-Biologics, HEAL PTDP, and URGenT biologics programs Performance Area 3: Toxicology SME(s) Toxicology SME consultants will be expected to provide senior-level expertise and contribute feedback and guidance on projects to the NIH and to LDT members through conference calls and by email. The role of the consultants may include but are not limited to the following responsibilities and tasks: a) Help establish toxicology endpoints and milestones for a project, recommend bioassays to be incorporated into a testing funnel or development plan, design toxicology and pharmacology studies, and interpret data delivered by CROs. b) In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage programs to facilitate lead optimization, IND enabling, and clinical studies c) Serve as a resource to the LDT for toxicology requirements, pharmacology and logistics to conduct biologics development activities for biologics from the preclinical stage through to the initial clinical stage d) Serve as the toxicology expert in order to identify potential developmental challenges and suggest strategies to address these challenges e) Collaborate on design of investigative toxicology studies in support of biologics development f) Review toxicology sections of regulatory filings provided by CROs or PIs g) Collaborate on the design of investigative studies in support of biologics development. h) Provide expert support of preclinical strategy development including that for neurological diseases i) Support in vitro and in vivo model development for neurological disease j) Support design and interpretation of in silico analyses and in vitro/ ex vivo screening strategies for oligonucleotides k) Support of design PK/PD and toxicology safety studies Performance Area 5 – Regulatory Affairs and Regulatory Operations SME(s) Regulatory Affairs consultants will provide advice and leadership in support of regulatory affairs strategy for NIH biologics programs. Consultants will be asked to provide guidance on IND-enabling studies to ensure that teams meet the guidelines and timelines of IND applications. Consultants will serve as the principal regulatory contact with NIH staff, PIs, and regulatory agencies, and may also be the primary regulatory representative to the FDA. The roles of the Regulatory Affairs and Regulatory Operations SME consultants may include but are not limited to the following responsibilities and tasks: a) Work within project teams to develop regulatory strategies, identify regulatory risks, and enable timely approval b) Advise NIH staff and project teams on issues related to regulatory strategy and identify areas of concern regarding developing regulations c) Provide input on and review specifications, methods, SOPs, protocols, reports, labeling, etc. for regulatory compliance d) Develop and manage timelines for regulatory submissions e) Work effectively to coordinate the activities of CROs and other consultants in the preparation of regulatory submissions as necessary f) Prepare and submit IND applications to the appropriate regulatory agency g) Prepare for and run regulatory agency meetings

顾问将提供有关科学过程的反馈和指导， 通过面对面会议、电话会议和电子邮件进行差距领域/需求评估。 顾问还需要提供有关超罕见疾病领域的信息， 最好重点关注神经系统疾病，这将有助于 NIH 更好地开展工作。 了解产品开发人员通过以下方式推动其治疗的要求 研究和开发阶段进入临床评估研究以及开发 具体的咨询职责将取决于专家的专业知识。 顾问和项目的需求。 绩效领域 1：生物制品化学、制造和控制 (CMC) 中小企业 制造各种生物治疗平台的主题专家，包括但不限于治疗性寡核苷酸（例如，反义寡核苷酸-ASO、小干扰RNA-siRNA等）、AAV、慢病毒或其他病毒载体疗法等模式，需要纯化蛋白、重组蛋白、肽、基于抗体和细胞的疗法以及离体生物制品 CMC 顾问提供。高级化学、制造和控制专业知识，并通过电话会议和电子邮件向 NIH 和 LDT 成员提供项目反馈和指导。 请注意，对于绩效领域 1，政府将考虑在一种或多种制造模式方面具有专业知识的中小企业顾问。 CMC 中小企业顾问的角色可能包括但不限于以下职责和任务： a) 对生物制造的充分性进行审查和评论，包括主要研究者 (PI) 和 CMO 提出的放大、分析方法开发和工艺开发（上游和下游加工）方法 b) 提供递送方法的指导，其中可能包括复杂的配方，例如聚合物、脂质体和其他纳米颗粒结构 c) 提供主细胞和工作细胞以及病毒库开发和测试方面的专家建议 d) 提供团队提出的生物制品工艺开发和生产计划的策略和反馈 e) 提供有关团队提出的治疗性寡核苷酸序列和合成过程的反馈 f) 提供对提议的生物制品制剂的反馈 g) 提供有关关键质量属性、发布测试等的反馈。 h) 每周或每两周评估 CMC 数据 i) 担任 CMC 专家，以确定潜在的产品制造挑战并提出应对这些挑战的策略 j) 陪同 NIH 工作人员或根据 NIH 工作人员的要求拜访与 NIH 签订合同的 CRO 和 CMO。 k) 检查设施并讨论 CRO/CMO 提议方法的适当性 l) 可能会要求 CMC 顾问评估拟议生物治疗的潜在可处理性（包括周围的 IP 空间） m) 合作设计调查研究以支持治疗开发项目 n) 与其他顾问、承包商和 NIH 工作人员合作，提供建议、战略规划和管理 CMC，以促进临床前评估和安全性测试、研究性新药 (IND) 提交和临床研究 o) 通过电话和电子邮件促进 LDT 关于指定的 CMC 工作的讨论 p) 为 BPN-Biologics、HEAL PTDP 和 URGenT 生物制品计划的持续开发和改进提供战略指导 绩效领域 3：毒理学中小企业 毒理学中小企业顾问应通过电话会议和电子邮件向 NIH 和 LDT 成员提供高级专业知识，并提供项目反馈和指导。顾问的职责可能包括但不限于以下职责和任务。 : a) 帮助建立项目的毒理学终点和里程碑，建议将生物测定纳入测试漏斗或开发计划，设计毒理学和药理学研究，并解释 CRO 提供的数据。 b) 与其他顾问、承包商和 NIH 工作人员合作，提供建议、战略规划和管理项目，以促进先导化合物优化、IND 启用和临床研究 c) 作为 LDT 的毒理学要求、药理学和后勤资源，以开展从临床前阶段到初始临床阶段的生物制剂开发活动 d) 担任毒理学专家，以确定潜在的发育挑战并提出应对这些挑战的策略 e) 合作设计毒理学研究以支持生物制剂的开发 f) 审查 CRO 或 PI 提供的监管文件的毒理学部分 g) 合作设计调查研究以支持生物制品的开发。 h) 为包括神经系统疾病在内的临床前策略制定提供专家支持 i) 支持神经系统疾病的体外和体内模型开发 j) 支持计算机分析和体外/离体的设计和解释 寡核苷酸筛选策略 k) 支持设计 PK/PD 和毒理学安全性研究 绩效领域 5 – 监管事务和监管运营 中小企业监管事务顾问将提供建议和领导，以支持 NIH 生物制品计划的监管事务策略。顾问将被要求提供 IND 支持研究的指导，以确保团队满足要求。 IND 申请的指导方针和时间表。顾问将作为 NIH 工作人员、PI 和监管机构的主要监管联系人，也可能是 FDA 的主要监管代表。 中小企业监管事务和监管运营顾问的角色可能包括但不限于以下职责和任务： a) 与项目团队合作制定监管策略、识别监管风险并及时获得批准 b) 就与监管策略相关的问题向 NIH 工作人员和项目团队提供建议，并确定有关制定法规的关注领域 c) 提供规范、方法、SOP、协议、报告、标签等方面的意见并进行审查，以确保合规性 d) 制定和管理监管提交的时间表 e) 有效协调 CRO 和其他顾问在准备必要的监管文件时的活动 f) 准备并向适当的监管机构提交 IND 申请 g) 准备并召开监管机构会议