Abstract:

Recent advances in regenerative medicine advanced therapies (RMAT) are revolutionizing health care by providing curative treatments for previously untreatable diseases. Flow cytometry assays have been used to measure critical quality attributes, including viability, identity, purity, and potency of the RMAT. However, the lack of reproducibility, comparability, and measurement confidence of results across various flow cytometry platforms, sites, and over time remain a major challenge. Moreover, high-quality flow cytometric datasets are mostly non-existent in the public domain, and this limits the potential development of artificial intelligence and machine learning (AI/ML) approaches to flow cytometry applications. Leveraging NIST’s long history and expertise in producing critically needed standards and reference materials, NIST launched the Flow Cytometry Standards Consortium (FCSC) in December 2020 to help developing the measurement solutions and standards needed to accelerate the translation, manufacturing, and approval of the RMAT. The FCSC serves as a neutral forum for stakeholders from industries, government agencies, academia, and other organizations to identify and address common challenges, share best practices, and accelerate the development of standards and reference materials towards quantitative and standardized flow cytometry.

To date, FCSC has established five active working groups (WGs) conducting interlaboratory studies to support instrument and assay standardization as well as characterization of gene delivery systems, build data repository infrastructure enabling multi-modal simultaneous data analysis for generating high-quality reference data standards, and develop AI-enhanced workflow for cytometric applications. These WGs cohesively work to drive the development and production of reference materials/standards, high-quality protocols and reference datasets. The data standards generated from the interlaboratory studies will enable testing of AI/ML approaches and bridging of flow cytometry data repositories to enhance data reproducibility, interoperability, and scalability. Other NIST measurement capabilities, e.g., dPCR, qPCR, NGS, and advanced imaging, are also utilized to support FCSC studies for the development of measurement solutions, standards, and best practices that will ultimately enable flow cytometry standardization for RMAT.