Regulatory Validation of Standardized Clinical Immunohistochemistry Controls

标准化临床免疫组织化学对照的监管验证

• 批准号: 9054981
• 负责人: Steven A Bogen
• 金额: $ 67.92万
• 依托单位: BOSTON CELL STANDARDS INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9054981
• 关键词: Address; Adherence; American; Antibodies; Antigens; Archives; Area; Automation; Biological Assay; Biopsy; Blood; Calibration; Chemistry; Clinic; Clinical; Clinical Sciences; Collaborations; Data; Data Base Management; Detection; Development; Diagnostic; Diagnostic tests; ERBB2 gene; Educational process of instructing; Feedback; Fostering; Funding; Furuncles; Glass; Glucose; Goals; Grant; Health; Histopathology; Hospitals; Housing; Human; Image Analysis; Immunohistochemistry; In Vitro; Institutes; Israel; Laboratories; Lead; Malignant Neoplasms; Marketing; Measures; Medical center; Methods; Microscope; Operative Surgical Procedures; Paper; Paraffin; Pathologist; Pathology; Performance; Phase; Problem Solving; Production; Proteins; Protocols documentation; Quality Control; Reagent; Regulatory Affairs; Regulatory Pathway; Reproducibility; Research; Resistance; Resources; Retrieval; Rights; Role; Running; Savings; Science; Sensitivity and Specificity; Series; Serum; Site; Slide; Small Business Innovation Research Grant; Solutions; Solvents; Specialist; Specificity; Staining method; Stains; Standardization; System; Technology; Technology Transfer; Test Result; Testing; Tissue Sample; Tissues; Translational Research; Validation; Vendor; clinical practice; college; commercialization; cost; design; human tissue; innovation; instrument; malignant breast neoplasm; novel; operation; performance tests; reagent standardization; research clinical testing; response; scale up; tissue preparation

DESCRIPTION (provided by applicant): The broad, long-term goal of this project is consistent, standardized diagnostic testing of surgical biopsies by immunohistochemistry (IHC). The methods to achieve this goal are well understood in the field of clinical laboratory testing: (1) standardization of reagents and protocols, (2) automation to reduce human errors, and (3) the use of standardized controls to provide test performance feedback. Over the last two decades, the first two of these three methods were implemented for IHC testing. This grant project focuses on the third - standardized controls. Current practice teaches non-standardized controls. Each histopathology lab typically procures test controls from leftover tissue samples in its own paraffin block archives. This is a strikingly different practice from clinical blood laboratories, where standardized and validated controls are produced in large quantities and sold through commercial vendors. Since each human tissue is a limited resource, present practice is inherently non-standardized. We have developed an innovative technical solution to this problem, summarized in a series of papers. After both in-house testing and a national study performed with the College of American Pathologists, the technology ran into a regulatory roadblock. As a "revolutionary" (rather than "evolutionary") assay control, the FDA set a high regulatory bar that made the project commercially unfeasible in its previous form. Using the same chemistry, we have re-designed the technology so as to address the previous regulatory roadblock. The Specific Aims of this Phase I - II Fast-Track proposal revolve around experimental validation, for regulatory purposes, of this re-designed new class of assay control. The Phase I Aims include analytical validation of the new product design, including an assessment of sensitivity, specificity, stability, and reproducibility. The Phase II aims address clinical validation, which will uniquely test and validate the role of standardization in IHC controls. Although our focus is initially in the area of breast cancer tests, this effort opens an entirely new market, to include other IHC controls products. The applicant group comprises a broad, multi-disciplinary team, including the original research team, statistical and database management staff from the Tufts Clinical & Translational Science Institute (CTSI), surgical pathologists, a regulatory affairs consultant, and an IHC commercial operations specialist. Phase II also includes a collaboration with the College of American Pathologists. At the conclusion of Phase II, we will have all of the FDA regulatory submission data for transition to commercialization. This project will lead to the creation of the first set of FDA-cleared nationall standardized IHC test controls. In converting clinical laboratories from a homebrew practice, the impact will be transformative, especially for the newer quantitative tests that demand a higher level of accuracy.

描述（由申请人提供）：该项目的广泛、长期目标是通过免疫组织化学 (IHC) 对手术活检进行一致、标准化的诊断测试。实现这一目标的方法在临床实验室检测领域是众所周知的：(1) 试剂和方案标准化，(2) 自动化以减少人为错误，以及 (3) 使用标准化控制来提供检测性能反馈。在过去的二十年中，这三种方法中的前两种被用于 IHC 测试。该资助项目重点关注第三项——标准化控制。当前的实践教导非标准化控制。每个组织病理学实验室通常从其自己的石蜡块档案中的剩余组织样本中获取测试对照。这与临床血液实验室的做法截然不同，在临床血液实验室中，标准化和经过验证的控制品是大量生产并通过商业供应商销售的。由于每个人体组织都是有限的资源，因此目前的做法本质上是非标准化的。我们针对这个问题开发了一种创新的技术解决方案，并在一系列论文中进行了总结。经过内部测试和与美国病理学家学会进行的全国性研究后，该技术遇到了监管障碍。作为一种“革命性的”（而不是“进化的”）检测控制，FDA 设定了很高的监管门槛，使得该项目以前的形式在商业上不可行。使用相同的化学物质，我们重新设计了该技术，以解决之前的监管障碍。这一第一阶段 - 第二阶段快速通道提案的具体目标围绕着出于监管目的，对这种重新设计的新型检测控制进行实验验证。第一阶段的目标包括新产品设计的分析验证，包括敏感性、特异性、稳定性和重现性的评估。第二阶段的目标是解决临床验证问题，这将独特地测试和验证标准化在 IHC 控制中的作用。尽管我们最初的重点是乳腺癌检测领域，但这一努力开辟了一个全新的市场，其中包括其他 IHC 对照产品。申请人群体由一个广泛的多学科团队组成，包括原始研究团队、来自塔夫茨临床与转化科学研究所（CTSI）的统计和数据库管理人员、外科病理学家、监管事务顾问和 IHC 商业运营专家。第二阶段还包括与美国病理学家学院的合作。在第二阶段结束时，我们将拥有所有 FDA 监管提交数据，以过渡到商业化。该项目将创建第一套经 FDA 批准的国家标准化 IHC 测试控制。将临床实验室从自制实践转变为变革性的影响，特别是对于要求更高准确度的新型定量测试而言。