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The Standards Coordinating Body for Gene, Cell, and Regenerative Medicines and Cell-Based Drug Discovery (SCB) supports the development and commercialization of regenerative medicine products by identifying and addressing industry-wide challenges through standards. Through extensive stakeholder engagement, the implementation of rapid microbial testing methods (RMTMs) was identified as a high-priority need that must be addressed to facilitate more timely release of products. Since 2017, SCB has coordinated efforts to develop standards for this area through surveys, weekly meetings, workshops, leadership in working groups and participation in standards development organizations. This article describes the results of these efforts and discusses the current landscape of RMTMs for regenerative medicine products. Based on discussions with stakeholders across the field, an overview of traditional culture-based methods and limitations, alternative microbial testing technologies and current challenges, fit-for-purpose rapid microbial testing and case studies, risk-based strategies for selection of novel rapid microbial test methods and ongoing standards efforts for rapid microbial testing are captured here. To this end, SCB is facilitating several initiatives to address challenges associated with rapid microbial testing for regenerative medicine products. Two documentary standards are under development: an International Organization for Standardization standard to provide the framework for a risk-based approach to selecting fit-for-purpose assays primarily intended for cell and gene therapy products and an ASTM standard guide focused on sampling methods for microbial testing methods in tissue-engineered medical products. Working with the National Institute of Standards and Technology, SCB expects to facilitate the process of developing publicly available microbial materials for inter-laboratory testing. These studies will help collect the data necessary to facilitate validation of novel rapid methods. Finally, SCB has been working to increase awareness of, dialog about and participation in efforts to develop standards in the regenerative medicine field. [ABSTRACT FROM AUTHOR]

The emergence of cell-based therapeutics has increased the need for high-quality, robust and validated measurements for cell characterization. Cell count, being one of the most fundamental measures for cell-based therapeutics, now requires increased levels of measurement confidence. The National Institute of Standards and Technology (NIST) and the US Food and Drug Administration (FDA) jointly hosted a workshop focused on cell counting in April 2017 entitled “NIST-FDA Cell Counting Workshop: Sharing Practices in Cell Counting Measurements.” The focus of the workshop was on approaches for selecting, designing and validating cell counting methods and overcoming gaps in obtaining sufficient measurement assurance for cell counting. Key workshop discussion points, representing approximately 50 subject matter experts from industry, academia and government agencies, are summarized here. A key conclusion is the need to design the most appropriate cell counting method, including control/measurement assurance strategies, for a specific counting purposes. There remains a need for documentary standards for streamlining the process to develop, qualify and validate cell counting measurements as well as community-driven efforts to develop new or improved biological and non-biological reference materials. [ABSTRACT FROM AUTHOR]

The article reflects on the need of defining quality attributes to enable measurement assurance for cell therapy products and highlights definition of critical quality attributes (CQA) as per the U.S. Food and Drug Administration.

The development of standards for the field of regenerative medicine has been noted as a high priority by several road-mapping activities. Additionally, the U.S. Congress recognizes the importance of standards in the 21st Century Cure Act. Standards will help to accelerate and streamline cell and gene therapy product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Although there is general agreement for the need of additional standards for regenerative medicine products, a shared understanding of standards is required for real progress toward the development of standards to advance regenerative medicine. Here, we describe the roles of standards in regenerative medicine as well as the process for standards development and the interactions of different entities in the standards development process. Highlighted are recent coordinated efforts between the U.S. Food and Drug Administration and the National Institute of Standards and Technology to facilitate standards development and foster science that underpins standards development. [ABSTRACT FROM AUTHOR]

Background aims Cell counting measurements are critical in the research, development and manufacturing of cell-based products, yet determining cell quantity with accuracy and precision remains a challenge. Validating and evaluating a cell counting measurement process can be difficult because of the lack of appropriate reference material. Here we describe an experimental design and statistical analysis approach to evaluate the quality of a cell counting measurement process in the absence of appropriate reference materials or reference methods. Methods The experimental design is based on a dilution series study with replicate samples and observations as well as measurement process controls. The statistical analysis evaluates the precision and proportionality of the cell counting measurement process and can be used to compare the quality of two or more counting methods. As an illustration of this approach, cell counting measurement processes (automated and manual methods) were compared for a human mesenchymal stromal cell (hMSC) preparation. Results For the hMSC preparation investigated, results indicated that the automated method performed better than the manual counting methods in terms of precision and proportionality. Discussion By conducting well controlled dilution series experimental designs coupled with appropriate statistical analysis, quantitative indicators of repeatability and proportionality can be calculated to provide an assessment of cell counting measurement quality. This approach does not rely on the use of a reference material or comparison to "gold standard" methods known to have limited assurance of accuracy and precision. The approach presented here may help the selection, optimization, and/or validation of a cell counting measurement process. [ABSTRACT FROM AUTHOR]