[Q&A] Taking the Temperature of Cell Therapy Logistics

[Q&A] Taking the Temperature of Cell Therapy Logistics

In this interview, we speak with Rob Jones, VP of Global BioServices at Cryoport Systems about the essential role of temperature-critical logistics in the success of cell and gene therapies and new standards that will impact the industry.
Q: Tell our readers about Cryoport Systems and the vital role you play in the delivery of temperature-controlled shipments for cell therapy companies. 
 
A: Cryoport has been involved in cryogenic supply chain for over 20 years now.  And we’ve built our reputation based on innovation, technology, robust systems, high-quality processes and procedures that allow us to meet the unique requirements of the industry with the services, and the quality of services, and more importantly, the consistency of service, that ensures that drugs get to patients in the best possible condition, at the right time.  Today, we’re supporting over 525 clinical trials just in the cell and gene therapy space, which is pretty much 50 percent of all active clinical trials in advanced therapies as well as six commercial cell therapies. 

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 Q: What are some of the key considerations for cell and gene therapy companies in terms of getting the clinical trial material, or the products, safely to the right place at the right time?

A: It is vitally important that therapy developers consider the distribution strategy on the same level of importance as their development and manufacturing strategies. Companies should start to think about this in the early phases of their clinical development as there is a wide range of options available including a vast array of shipping devices, containers, but also companies that will provide the logistics.  If this is an autologous therapy, it’s very likely the last possible chance for that patient.  The product is irreplaceable. If you look at it in that context, then how do you view the company that’s providing the logistics services for you?  Do you base your decision on the cost of their service?  Or do you base it on their capabilities and technology, and the quality systems that they use, that will assure the safe delivery of the therapy?  I always encourage cell therapy developers to really delve deep into the capabilities of possible logistics partners, their quality systems, their historical records and historical data.  At Cryoport, we class ourselves not only as a logistics company, but first and foremost we’re a technology and an information company.  We keep all historical records from, every single shipment we’ve ever done.  So, we’ve got a significant amount of data, nearly 400,000 shipments worth of data, that we can analyze and pass into really determining the best way of shipping any product, at any temperature, anywhere in the world. 
 
Q: What is the significance of the new ISO standards for transportation of cells for therapeutic use?

A: The first thing to note is that any ISO standard is not a regulation but a set of best practices that are voluntary.  However, GMP and regulatory auditors will understand these recommendations as best practice.  The new standard that you’re referring to is ISO 21973, which was published in July 2020.  It is significant in that it is the first time ever that a standard has been published relating to transportation of cellular material. ISO 21973 is a recognition that now as the industry has got to a certain point, there needs to be some consistency brought into the way these materials are handled in the supply chain. The standardization will begin to create consistent services, consistent products and equipment, and consistent specifications that will have the effect of driving down cost, as well as improving quality of shipment. This ensures that these drugs will get to the right destination, at the right time, in the right condition. 
 
The standard has six key elements. The first is creation of a cell transportation specification. The cell therapy developer and the transport service provider need to have a mutual understanding of what the material is, what the nature of the material is, how it needs to be handled, how it needs to be labeled and the actual transportation systems to be used. These factors must be mutually agreed in advance.
 
The next section relates to the shipping container and labeling and outlines precautions that should be taken in terms of the validation, requalification and cleanliness. How the materials are labeled, for example, can have a significant bearing on international transportation and ensuring that it doesn’t get held up in border controls, making sure all the documentation is correct and the right labels are used.  Then there is the operations piece which is how the service provider conducts the transportation.   
 
The next section is about the need to work with organizations that have a robust quality system in place including training of personnel, documentation, SOPs, corrective and preventative actions and continuous improvement.  These should be clearly laid out in a quality policy, and that’s one of the first things that you should ask your logistics company about is their quality management system. 
 
Another element focuses on in-transit storage.  So many shipments, especially international, maybe have multiple legs and between each, the shipper will have to be stored in a warehouse until it goes onto the next leg of the journey. There needs to be some provision to make sure that wherever that shipper is stored, it’s in a safe, secure environment that’s appropriate for the storage of these highly fragile, delicate products. There should be assurances of the warehousing areas if the shipper ever has to be stored temporarily. 
 
Finally, there needs to be documentation of every step of the transportation process that involve multiple handoffs to different organizations. Even the provenance of the shipping device, historical records, maintenance, cleaning records, qualification and every step in the transportation has to be documented and available for audit. 
 
Q: Tell me about Cryoport’s involvement in the development of this standard.

A: These standards are developed with a group of industry key opinion leaders, academic organizations and government organizations.  The 21973 standard has been in development for about seven years, and for the majority of that time, Cryoport have been involved as an industry subject matter expert.  We helped draft some of the wording in the standards, and a lot of this was based on our own experience.  We’ve really been doing much of what has been laid down in the standard for many, many years. As I mentioned at the start, we’ve been doing this for 20 years, and many of these processes and recommendations have been our routine processes for the majority of those years.
 
Q: How does Cryoport tackle the challenges of temperature-controlled logistics? 

A: That’s probably the biggest question you’ve asked me so far.  We ensure that when we are shipping these products, they are in an environment as close to what they would have experienced straight after manufacturing; maintaining the environment is essential.  In terms of validation and qualification, the shipper must perform the same way on every shipment and the only way you can do that is to requalify a reusable shipper every single time.  Not just once a year, or once every six months, it has to be every single shipment. We must ensure that there’s going to be no contamination risk, so we have systems that can decontaminate the surfaces of the shipping device. We’ve also worked with an independent specialist laboratory to devise a process to decontaminate and clean every single shipper when it comes back, to reduce any potential surface contamination by up to six log reduction.  But we also go further than that. We’ve devised a system whereby we can separate our fleet of advanced therapy shippers, and these are shippers that will only ever be used on cell and gene therapy products for human therapeutic purposes. They’re visually different, they’re different colors, and they’re handled by a different group of people in our facilities.  The electronic segregation ensures that you can never accidentally use a general-purpose shipper for a cell therapy shipment.  And again, this is an important consideration as there’s elements of this that are built into the 21973 standard as well.  Cryoport is also one of the first companies that provides near real-time monitoring, GPS tracking, shock alerts and tilt alerts. 
 
We’re constantly striving to develop new products and new services. Last year, our parent company, Cryoport, Inc. acquired MVE Biological Solutions, the world leader in cryogenic storage vessels and shipping containers, and CRYOPDP, the third largest specialist courier company in the world. We now have a much wider range of temperatures and shipper types that we can offer our customers.  We will also be introducing new shipper technologies that have never been seen before that will help mitigate risk in transportation even further.  This year sees the launch of our new BioServices business, where for the first time in Cryoport’s history, we’ll now be providing onsite storage capabilities including GMP-compliant temperature-controlled storage, packaging, labeling, and distribution.  We’re about to open two new facilities in the U.S. that will provide these services, and we’ll be extending this network of BioServices globally in the future.  In this rapidly evolving and growing market, we are investing in today and the future as well. 
 
Advanced Therapy Shippers™
Cryoport’s Advanced Therapy Shipper™ product line, a first-of-its-kind fleet, contains shippers dedicated exclusively to human cell and gene supply chain management for both clinical and commercial therapies. The Advanced Therapy Shipper™ fleet was specifically designed to meet ISO 21973 − General requirements for transportation of cells for therapeutic use
We’re constantly striving to develop new products and new services. Last year, our parent company, Cryoport, Inc. acquired MVE Biological Solutions, the world leader in cryogenic storage vessels and shipping containers, and CRYOPDP, the third largest specialist courier company in the world. We now have a much wider range of temperatures and shipper types that we can offer our customers.  We will also be introducing new shipper technologies that have never been seen before that will help mitigate risk in transportation even further.  This year sees the launch of our new BioServices business, where for the first time in Cryoport’s history, we’ll now be providing onsite storage capabilities including GMP-compliant temperature-controlled storage, packaging, labeling, and distribution.  We’re about to open two new facilities in the U.S. that will provide these services, and we’ll be extending this network of BioServices globally in the future. In this rapidly evolving and growing market, we are investing in today and the future as well. 
 
Chain of Compliance®
Precision medicine requires end-to-end traceability: everything from chain of custody to chain of condition, to chain of identity. But the fragility of regenerative medicine therapies – and the need to more effectively manage risk– means that a fourth chain will soon be a regulatory requirement: The Chain of Compliance®. Chain of Compliance® provides full traceability of the equipment and processes used in managing the environmental control of the commodity. This includes equipment performance, commodity history, equipment requalification, calibration history and correlation of in-field events
ISO 21973 Requirement   How Cryoport Adheres to the Requirement
Traceability
Chain of Compliance®
Segregation of Human- vs. Animal-derived products
Advanced Therapy Shipper™ fleet
Cleaning & Decontamination
Veri-Clean™
Validation, Verification, and Qualification
ISO 9001:2015 Accreditation
Chain of Custody & Tracking
Cryoportal® & Live View™