BIOLOGICS SUBJECT MATTER EXPERT (SME) CONSULTING SERVICES

表现领域1：生物制品化学、制造及控制(CMC)中小企业(S) 需要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RNAs-siRNAs等)、AAV、慢病毒或其他病毒载体治疗、纯化蛋白、重组蛋白、多肽、抗体和细胞治疗以及体外细胞治疗。生物制品CMC顾问将提供高级化学、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成员提供关于项目的反馈和指导。 请注意，对于绩效领域1，政府将考虑具有一种或多种制造模式专业知识的中小企业顾问。 CMC中小企业顾问的职责可能包括但不限于以下职责和任务： A)审查和评论生物制造的充分性，包括由首席调查员和CMO提出的扩大规模、分析方法开发和工艺开发(上游和下游处理)方法 B)提供有关给药方法的指导，其中可能包括复杂的制剂，如聚合物、脂质体和其他纳米颗粒构造 C)就母体和工作细胞及病毒库的开发和测试提供专家咨询 D)就团队提出的生物制剂工艺开发和制造计划提供战略和反馈 E)就该小组提出的治疗性寡核苷酸序列和合成过程提供反馈 F)就拟议的生物制品配方提供反馈 G)就关键质量属性、发布测试等提供反馈。 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战略建议 J)陪同国家卫生研究院的工作人员，或应国家卫生研究院工作人员的要求，探访与国家卫生研究院有合同的CRO和CMO。 K)检查设施并讨论CRO/CMO拟议方法的适当性 L)CMC顾问可能会被要求评估拟议的生物疗法的潜在可处理性(包括周围的IP空间) M)合作设计调查性研究，以支持治疗学开发项目 N)与其他顾问、承包商和NIH工作人员合作，为CMC提供建议、战略规划和管理，以促进临床前评估和安全测试、研究新药(IND)提交和临床研究 O)通过电话和电子邮件促进LDT关于分配的CMC工作的讨论 P)为BPN-生物制品、医疗技术方案和紧急生物制品方案的持续发展和改进提供战略指导 绩效领域5-监管事务和监管运营中小企业(S)监管事务顾问将为NIH生物制品项目的监管事务战略提供建议和领导。将要求顾问就促进可持续发展的研究提供指导，以确保团队符合可持续发展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。 监管事务和监管业务中小企业顾问的职责可能包括但不限于以下职责和任务： A)在项目团队内工作，以制定监管战略，识别监管风险，并及时获得批准 B)就与监管战略有关的问题向国家卫生研究院工作人员和项目团队提供咨询，并确定与制定监管有关的关切领域 C)提供关于规范、方法、标准操作规程、协议、报告、标签等的信息，并对其进行审查，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和其他顾问在必要时准备法规呈件方面的活动 F)准备IND申请并向适当的管理机构提交 G)筹备和主持监管机构会议 表现范畴8-品质保证(QA)中小企业(S) 质量保证中小型企业顾问将对NIH生物制品计划下支持生物疗法的产品开发和临床评估的活动提供质量监督。 质量保证中小企业将： A)起草、审查和批准监管备案文件的相关章节。 B)就最佳做法和流程向产品开发团队提供建议 C)确保CRO/CMO遵守法规和质量要求 D)负责进行质量检查 E)负责偏差评估 F)支持对制造CMO设施和研究的审计 G)支持对毒理学研究组织设施和研究的审计 H)陪同国家卫生研究院的工作人员，或应国家卫生研究院工作人员的要求，探访与国家卫生研究院有合同的CRO和CMO。检查设施并讨论CRO/CMO建议方法的适当性 I)根据需要进行其他现场审计和研究报告审计

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 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 Performance Area 8 – Quality Assurance (QA) SME(s) The Quality Assurance SME Consultant will provide quality oversight of activities supporting product development and clinical evaluation of biological therapeutics under NIH biologics programs. The Quality Assurance SME will: a) Draft, review, and approve relevant sections of regulatory filings. b) Advise product development team on best practices and processes c) Ensure CRO/CMO compliance to regulations and quality requirements d) Be responsible for conducting quality checks e) Be responsible for deviation assessment f) Support audits of manufacturing CMO facilities and studies g) Support audits of toxicology CRO facilities and studies h) Accompany NIH staff or visit, at NIH staff request, CROs and CMOs under contract to the NIH. Inspect facilities and discuss appropriateness of CRO/CMO proposed methodology i) Conduct other site audits and study report audits as required