Dr. Sheng Lin-Gibson is the Chief of Biosystems and Biomaterials Division at the U.S. National Institute of Standards and Technology (NIST) and directs its Regenerative Medicine Programs. She serves as the Convenor of ISO/TC 276: Biotechnology Working Group 3: Analytical Methods as well as the Chairperson for the U.S. Mirror Committee to ISO/TC 276. She leads or contributes to the development of several international standards particularly relevant to cell and gene therapy manufacturing and characterization. She has coauthored over 60 peer-reviewed publications, served on numerous NSF, NIH, and NIST expert review panels, and is a recipient of three Department of Commerce Bronze Medals.
In this installation of the “Bioprocess and Bioanalytics” blog, we will hear from Sheng-Lin Gibson on what standards are, and why they are enormously important to accelerating the field of cell and gene therapy.
The transition from research and development to manufacturing and commercialization for a broad range of advanced therapeutics, including cell therapy, gene therapy and tissue engineered product, has led to an increased need for standards. The purpose is to accelerate and streamline product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Development of standards specific for these advanced therapeutics was identified as a priority by the National Institute of Standards and Technology (NIST) Advanced Manufacturing Technology Consortia (AMTech) funded by the U.S. National Cell Manufacturing Consortium Roadmap, NIIMBL and BioFabUSA, and survey results conducted by the Alliance for Regenerative Medicine.
What is a standard?
Despite increased calls for standards development, there is general confusion about the type and the purpose of standards used for advancing industry-specific products. Many types of standards exist (Figure 1) and can help to 1) enable common understanding (including term and definition or interpretation of data and results); 2) provide common rule, condition, guidelines or characteristics for products or related processes and production methods and facilities; and, 3) enable tractability and comparability through a common material (such as a reference material).
When developing standards, a shared understanding for the type, scope/requirements, purpose/intended use, and affected entities is necessary. In addition, a cohesive strategy is needed for making real progress towards the development of a standards infrastructure for cell and gene therapies. Coordination is required to ensure that standards do not adversely affect technology development and innovation, restrict commerce, or duplicate/conflict with existing standards. In addition, broad input from stakeholders and subject matter experts is essential to develop the standards to address the most pressing needs.
Various standards pertinent to advanced therapies have been developed or are under development within multiple international Standards Developing Organizations (SDOs), including several ISO and ASTM International Technical Committees. One technical committee, with a number of standardization efforts particularly relevant for cell and gene therapy, is ISO/TC 276: Biotechnology, which is working to develop standards for biobanking and bioresources, bioprocessing, analytical methods, and data process and integration.
Current efforts that require stakeholder input are listed below:
- ISO 20391-1Biotechnology — Cell counting — Part 1: General guidance on cell counting methods
- ISO/CD 20391-2Biotechnology — Cell Counting — Part 2: Experimental design and statistical analysis to quantify counting method performance
- ISO/AWI 23033Biotechnology — Cell Characterization — General guide for characterization of human cells for therapeutic applications
- ISO/AWI 20395-1Biotechnology — Guidelines for evaluating the performance of targeted nucleic acid quantification methods — Part 1: qPCR and dPCR
Additional standards projects can be found at the ISO website.
Standards are also being developed within national standards bodies, such as the BSI in the U.K. and ATCC and CLSI within the U.S. In addition, a number of organizations have developed their own best practices and/or accreditation standards. Industry has also voiced its desire to leverage existing standards to the extent possible.
NIST and SCB
Recognizing the need for coordinated standard development, the 21st Century Cures Act of 2016 directs the U.S. Food and Drug Administration (FDA), in consultation with NIST and stakeholders, to “facilitate an effort to coordinate and prioritize the development of standards and consensus definitions of terms.” In response, the FDA awarded a one-year contract to Nexight Group. Nexight Group, with the help of Standards Coordinating Body (SCB), is engaging with experts to recommend processes and outline a strategic plan for developing standards in regenerative medicine and advanced therapies. NIST and SCB have a Memorandum of Understanding to collaborate on efforts for the development and advancement of standards for cellular and gene therapies, other regenerative medicine therapies and cell-based drug discovery. The collaborative activities include:
- Identifying areas of mutual interest for R&D activities;
- Providing educational tools for standards development and use;
- Jointly planning conferences and workshops to engage stakeholders;
- Disseminating information regarding existing standards; and,
- Developing web content with information about standards for regenerative medicine.
NIST additionally has laboratory programs that support the development of documentary standards and reference materials (also known as reference standards). As well, NIST actively interacts with the FDA through laboratory collaborations, hosting of joint workshops, and coordinated standards development efforts. NIST also collaborates with industry and academia via consortia and/or ad hoc mechanisms to develop measurement solutions and technology. Examples of NIST consortia include the Quantitative Flow Cytometry Consortium and the NIST Genome Editing Consortium.
In summary, standards are enormously important for accelerating the field of cell and gene therapy. Development of science-based standards, supported by high quality data and expert input, as well as upstream coordination and downstream education, are critical to the realization of a robust standards infrastructure to enable technology innovation, accelerate translation, and ensure the quality and consistency of manufacturing.
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