SBIR-STTR Award

The broad long term goal of this project is consistent standardized diagnostic testing of surgical specimens by immunohistochemistry IHC The methods to achieve this goal are well understood in the field of clinical laboratory testing standardization of reagents and protocols automation to reduce human errors and 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 IHC 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 We have developed an innovative technical solution summarized in a series of published journal articles Over the last years and with NCI funding our breast cancer IHControlsTM panel for HER ER and PR tests recently entered clinical testing and will be submitted for regulatory clearance this year This Direct to Phase II proposal addresses clinical IHC laboratory practice beyond breast cancer testing We will expand the IHControlsTM product portfolio from analytes HER ER andamp PR to The new IHControlsTM panels comprise the General Pathology Melanoma Lung Cancer and Hematopathology test portfolios This ten fold expansion is feasible with funding from a single Phase II grant because a we have already worked out the nuances of product design manufacture under cGMP and testing and b the additional analytes will mostly be class I products The Specific Aims of this proposal are creation of the new IHControlsTM panels analytical validation including testing for sensitivity specificity product stability and manufacturing reproducibility and clinical validation including testing for precision reference interval expected level of staining and limit of detection The applicant group comprises a broad multi disciplinary team including the MDP Randamp D team statistical support from the Tufts Clinical andamp Translational Science Institute CTSI surgical pathologists and consultants for regulatory affairs quality systems and IHC commercial operations Converting clinical laboratories from homebrew to standardized controls will be a transformative change This project is to fund the development and clinical regulatory studies for a new first in class type of clinical test control in the field of cancer immunohistochemistry IHC testing These clinical IHC test controls will solve an important problem in the field of cancer testing relating to variability and inconsistency in IHC testing Clinical test controls are important for promoting test reproducibility and consistency amongst hospital laboratories These are the first standardized and quantificable IHC controls

The broad, long-­?term goal of this project is consistent, standardized diagnostic testing of surgical specimens 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 IHC 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. We have developed an innovative technical solution, summarized in a series of published journal articles. Over the last 2 years and with NCI funding, our breast cancer IHControlsTM panel for HER-­?2, ER, and PR tests recently entered clinical testing and will be submitted for regulatory clearance this year (2016). This Direct-­?to-­?Phase II proposal addresses clinical IHC laboratory practice beyond breast cancer testing. We will expand the IHControlsTM product portfolio, from 3 analytes (HER-­?2, ER, & PR) to 30. The new IHControlsTM panels comprise the General Pathology, Melanoma, Lung Cancer, and Hematopathology test portfolios. This ten-­?fold expansion is feasible with funding from a single Phase II grant because: (a) we have already worked out the nuances of product design, manufacture under cGMP, and testing, and (b) the additional analytes will mostly be class I products. The Specific Aims of this proposal are: (1) creation of the new IHControlsTM panels, (2) analytical validation, including testing for sensitivity, specificity, product stability, and manufacturing reproducibility, and (3) clinical validation, including testing for precision, reference interval (expected level of staining), and limit of detection. The applicant group comprises a broad, multi-­?disciplinary team, including the MDP R&D team, statistical support from the Tufts Clinical & Translational Science Institute (CTSI), surgical pathologists, and consultants for regulatory affairs, quality systems, and IHC commercial operations. Converting clinical laboratories from homebrew to standardized controls will be a transformative change.

Public Health Relevance Statement:
This project is to fund the development and clinical regulatory studies for a new, first-in- class, type of clinical test control in the field of (cancer) immunohistochemistry (IHC) testing. These clinical IHC test controls will solve an important problem in the field of cancer testing, relating to variability and inconsistency in IHC testing. Clinical test controls are important for promoting test reproducibility and consistency amongst hospital laboratories. These are the first standardized and quantificable IHC controls.

Project Terms:
Accreditation; Address; Antigens; Archives; Automation; Bacteriophage M13; Biological Assay; Blood; Clinical; clinical practice; Clinical Sciences; combinatorial; commercialization; cost; cost effective; Cyclic GMP; Data; design; Detection; Development; Diagnostic tests; Epitopes; ERBB2 gene; Estrogen Receptors; Failure; Feedback; Fostering; Funding; Glucose; Goals; Grant; Hand; Hematopathology; Histopathology; hospital laboratories; human error; Immunohistochemistry; innovation; Institutes; journal article; Laboratories; Libraries; malignant breast neoplasm; Malignant neoplasm of lung; Malignant Neoplasms; Maps; Measures; melanoma; Methods; Notification; operation; Operative Surgical Procedures; Paraffin; Pathologic; Pathologist; Pathology; Patients; Peptides; performance tests; Phase; Price; Progesterone Receptors; programs; Proteins; Protocols documentation; Publications; Publishing; Quality Control; reagent standardization; Regulatory Affairs; Reproducibility; research and development; research clinical testing; Sampling; Sensitivity and Specificity; Series; Serum; Small Business Innovation Research Grant; Specificity; Specimen; Stains; Standardization; System; Technology; Test Result; Testing; Tissue Sample; Translating; Translational Research; United States National Institutes of Health; Validation; Vendor; Work