-Dr. IJ Arora
In leading my team of consultants, trainers and auditors, I have emphasized the importance of the combined or integrated approach to management systems (MS). Very often the client only needs a discrete system to one standard to be seen. Which is alright, after all in an audit the objective, scope and criteria are decided by the audit client. QMII Team recently worked with a client on the implementation of ISO 21973 and this article encompasses my personal thought and my professional experience of using the standard.
ISO 21973 is a relatively new standard (published in 2020) and it outlines general requirements for the transportation of cells for therapeutic use. It aims to address the unique challenges of transporting these sensitive biological materials by focusing on traceability, whereby ensuring complete tracking of the equipment, processes, and logistics involved in maintaining the cell’s environment during transit. This includes the “Chain of Custody,” “Chain of Condition,” and “Chain of Identity.” Chain of Custody is mentioned in the standard; however, chain of condition and Chain of identity are not mentioned but implied. ISO 21973 provides guidance on the management of evidence in the justice system. It covers various aspects of evidence handling, including its collection, preservation, analysis, and presentation in court. Chain of Condition refers to the documented history of how evidence has been handled from the time since when it is collected to its presentation in court. This includes information about who handled the evidence, when, and under what conditions. Chain of Identity refers to the documented history of how the identity of the evidence has been maintained. This includes information about how the evidence was marked, labeled, and stored to ensure that it can be uniquely identified and linked to its source. The chain of condition helps to ensure the integrity and authenticity of the evidence. The Chain of Identity helps to prevent evidence from being tampered with or substituted. Both the Chain of Condition and the chain of identity are critical for ensuring the admissibility of evidence in court. By maintaining accurate and complete records of how evidence are being handled, investigators and prosecutors can help to build a strong case and increase the likelihood of a successful conviction.
ISO 21973:2020 specifically addresses the “Chain of Condition” and “Chain of Identity” within the context of transportation of cells for therapeutic use. Chain of Condition, this concept is central to the standard. It emphasizes the importance of maintaining the integrity and viability of the cells throughout the transportation process. This includes meticulous tracking of environmental conditions (temperature, humidity, etc.) and ensuring that these conditions remain within acceptable limits. In the chain of Identity, the standard stresses the need to unequivocally identify the transported cells at all times. This involves robust labeling, tracking systems, and documentation to prevent mix-ups or substitutions. ISO 21973 recognizes the critical role of both “Chain of Condition” and “Chain of Identity” in ensuring the safety and efficacy of cell-based therapies, even though the term is not specifically used. The standard provides a framework for establishing and maintaining these chains, helping to minimize risks associated with transportation. I find this, not explicitly mentioning the specific clauses for “Chain of Condition” and “Chain of Identity”, to be a shortcoming too. The concepts are integrated throughout the standard, particularly in sections related to, transportation planning and risk assessment. These sections emphasize the importance of considering and mitigating risks that could affect the condition or identity of the cells during transport. Temperature control and monitoring, by maintaining appropriate temperature is crucial for cell viability (Chain of Condition). Packaging and labeling needs proper packaging and clear, unambiguous labeling are essential for maintaining cell identity and preventing mix-ups. Transportation logistics are addressed in the standard as need for secure transportation, including measures to prevent contamination, damage, and unauthorized access. Documentation and record-keeping are a requirement. Detailed records of all transportation activities, including temperature logs, handling information, and chain-of-custody documentation, are vital for demonstrating compliance with the standard.
The standard addresses risk management, emphasizing the need for thorough risk assessments to identify and mitigate potential hazards during transportation. It mentions the need for a quality management system in promoting the integration of transportation considerations into the overall management system for cell and gene therapies. I think a clear mention of genes in the introduction or as an appendix or perhaps somewhere as a note would have made the standard robust. I agree the focus in ISO 21973 is on Cells. The standard is titled “General requirements for transportation of cells for therapeutic use.” It focuses on the overall handling and transportation of cells, regardless of their specific origin or modification. The broad scope, “Cells” encompasses a wide range of biological materials, including those derived from tissues, organs, and even genetically modified organisms. Agreed it is an evolving field. Cell and gene therapies are rapidly evolving. A specific mention of “genes” could have limited the standard’s applicability as the field advances. However, the principles of “Chain of Condition” and “Chain of Identity” are fundamental for any biological material, including genetically modified cells. Therefore, these principles implicitly apply to gene therapies. Explicitly mentioning “gene therapies” or “genetically modified cells” could enhance clarity and provide a clearer framework for handling these specialized products. The standard should emphasize the unique challenges and considerations associated with transporting gene therapies, such as the potential for contamination or the need for specialized handling protocols. As the TC (technical committee) looks to future revisions of ISO 21973 hopefully they will incorporate more specific guidance on transporting gene therapies as the field progresses. So though “gene” is not explicitly mentioned, the principles and requirements outlined in ISO 21973 are applicable to the transportation of cells for gene therapy. As the field evolves, the standard may be further refined to include more specific guidance on handling these complex therapies. As it exists it can lead to doubts in the minds of the implementer and make auditing without specific requirements difficult.
It meets a felt need and is a timely standard. While it may present some initial challenges, the long-term benefits of increased quality and patient safety are likely to outweigh the costs.
