Abstract
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.
Key Words
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References
The United States pharmacopeia. 1223. Validation of Alternative. Microbiological Methods.
The United States pharmacopeia. 71. Sterility
Ph. Eur. 2.6.1. Sterility
- Opportunities and challenges of real-time release testing in biopharmaceutical manufacturing.Biotechnology and Bioengineering. 2017; 114: 2445-2456
- Comprehensive Evaluation of Compendial USP<71>, BacT/Alert Dual-T, and Bactec FX for Detection of Product Sterility Testing Contaminants.J Clin Microbiol. 2019; 57 (e01548-18)
- Evaluation of growth based rapid microbiological methods for sterility testing of vaccines and other biological products.Vaccine. 2011; 29: 8012-8023
- Machine learning for microbial identification and antimicrobial susceptibility testing on MALDI-TOF mass spectra: a systematic review.Clin Microbiol Infection. 2020; S1198-743X
- Strategy and validation of a consistent and reproducible nucleic acid technique for Mycoplasma detection in advanced therapy medicinal products.Biologicals. 2020; 64: 49-57
- Applications of Flow Cytometry to Characterize Bacterial Physiological Responses.Biomed Research International. 2014; (2014:461941)
- Evaluation of flow cytometry for the detection of bacteria in biological fluids.PLoS ONE. 2019; 14: 8
Standards Coordinating Body. April 2019. Community Perspectives Needed Standards in Regenerative Medicine. retrieved from https://www.standardscoordinatingbody.org/needed
- Perspectives for Consideration in the Development of Microbial Cell Reference Materials.Cancer Epidemiol Biomarkers Prev. 2019; 28: 1949-1954
21 CFR 610.12 “Sterility.”
- Guidance for Industry Guidance for Human Somatic Cell Therapy and Gene Therapy. FDA, Rockville (MD)1998
- Guidance for Industry: Class II Special Controls Guidance Document: Cord Blood Processing System and Storage Container. FDA, Rockville (MD2011
ISO/WD 24190. Risk based approach for design and validation of methods for rapid microbial detection in bioprocesses. Geneva, Switzerland: ISO; under development. https://www.iso.org/standard/78060.html?browse=tc
ASTM WK 70143. New Guide for Sampling Methods of Tissue Engineered Medical Products (TEMPs) for Sterility Assurance. PA, USA: ASTM; under development. https://www.astm.org/DATABASE.CART/WORKITEMS/WK70143.htm
- Autologous CAR T-cell therapies supply chain: challenges and opportunities.Cancer Gene Therapy. 2020;
- Rapid Microbial Identification and Antibiotic Resistance Detection by Mass Spectrometric Analysis of Membrane Lipids.Analytical Chem. 2019; 91: 1286-1294
- Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment.Environ Toxicol Chem. 2010; 29: 730-741
- Review of 62 risk analysis methodologies of industrial plants.Journal of Loss Prevention in the Process Industries. 2002; 15: 291-303
- Molecular characterization of microbial contaminants isolated from umbilical cord blood units for transplant.Braz J Infect Dis. 2015; 19: 571-577
- A Fast and Easy ATP-Based Approach Enables MIC Testing for Non-resuscitating VBNC Pathogens.Front Microbiol. 2019; 10: 1365
- Evaluation of an ATP-Bioluminescence Rapid Microbial Screening Method for In-Process Biologics.PDA J Pharm Sci Techno. 2018; 72: 574-583
- A review of methods for the detection of pathogenic microorganisms.Analyst. 2019; 144: 396-411
- Evaluation of flow cytometry for the detection of bacteria in biological fluids.PLoS ONE. 2019; 14: 8
- ELISA-Based Identification and Detection of Microbes. Analyzing Microbes.Springer Protocols Handbooks. Springer, 2013
- High-throughput and facile assay of antimicrobial peptides using pH-controlled fluorescence resonance energy transfer.Antimicrob Agents Chemother. 2006; 50: 3330-3335
- A single tube system for the detection of Mycobacterium tuberculosis DNA using gold nanoparticles based FRET assay.Journal of Microbiological Methods. 2017; 139: 165-167
- Risk Assessment Approach to Microbiological Controls of Cellular Therapies.PDA J Pharm Sci Technol. 2020;
- A Process-Oriented Risk Assessment Methodology for Manufacturing Processes.in: IFAC. Elsevier, 2013 (June)
- Manufacturing Practice Guide for Active Pharmaceutical Ingredients. ICH, 2016
- Enhancing CAR T cell efficacy: the next step toward a clinical revolution.Expert Rev Hematol. 2020; 13: 533-543
- Standard requirement of a microbiological quality control program for the manufacture of human mesenchymal stem cells for clinical use.Stem Cells Dev. 2014; 23: 1074-1083
- Risk management: guidelines on principles and implementation of risk management.ISO, Geneva, Switzerland2018
- Risk analysis: assessing uncertainties beyond expected values and probabilities.Wiley& Sons, 2008
- ICH. 2005;
- (Value, Risk)-Based Performance Evaluation of Manufacturing Processes.Information Control Problems in Manufacturing. 2012; 14: 1586-1591
- Microbial identification strategies in the pharmaceutical industry.PDA J Pharm Sci Technol. 2006; 60: 111-123
- Managing design processes: a risk assessment approach.IEEE Transactions on Systems, Man, and Cybernetics-Part A: Systems and Humans. 1996; 26: 749-759
- Validation Study of Rapid Assays of Bioburden, Endotoxins and Other Contamination.Biocontrol Sci. 2016; 21: 63-72
ISO/IEC 17029: 2019. Conformity assessment—general principles and requirements for validation and verification bodies. Geneva, Switzerland: ISO. 2019.
The United States pharmacopeia. <1071>. Rapid Sterility Testing of Short-life Products: A Risk Based Approach.
- Validation of Analytical Procedures: Text and Methodology. Q2(R1). ICH, 2005
Standards Coordinating Body. https://www.standardscoordinatingbody.org/other-activities.
Article info
Publication history
Published online: March 26, 2021
Accepted:
July 9,
2020
Received:
November 12,
2019
Identification
Copyright
© 2021 Published by Elsevier Inc. on behalf of International Society for Cell & Gene Therapy.
