The 250ml cassette standard: Let’s think inside the box!

In a January 2019 statement from the FDA, Scott Gottlieb, MD and Peter Marks, MD, Ph D said they anticipate that by 2020, they will be receiving more than 200 INDs per year in cell and gene therapy. They went on to say that by 2025, they predict the FDA will be approving 10-20 cell and gene therapy products a year based on an assessment of the current pipeline and clinical success rates of these products.

As these products advance through various stages of approval, supply chain managers are tasked with manufacturing and delivery of final products. While the intricacies of bioprocessing and developing new cell and gene therapy products are layered in expertise and IP – one simple, yet underestimated aspect is defining the final product delivery cassette.

The cassette is simple. It’s an aluminum frame used to protect blood bags and assist in heat transfer during the controlled-rate freeze step of product development. The cassette has no real impact on bioprocessing. It is simply the delivery container for the payload. Common cassette sizes are 25mL, 50mL, 150mL, and 250mL – the size common in CAR-T.

 

Cassette with actual dimensions.jpg

Current CAR-T products use a 250mL cassette with the same dimensions. These dimensions are what companies like Brooks Life Sciences are designing to.

 

Manufacturers of equipment used for delivery and storage of these cassettes are challenged in one simple way: No standard outer dimensions exist for designing a 250mL cassette. Depending on the manufacturer, a 250mL cassette could vary in dimensions on either side – or in the thickness of the cassette. Does this remind anyone of the ANSI/SBS standards development? This has significant unrealized impact on industry economics and efficiencies.

To help illustrate this point, let’s look at the shipping industry. Years ago, product was brought to the shipyard, train station, or depot to be loaded for distribution. Over time, this evolved into manufactured goods being pre-loaded into shipping containers. The containers helped streamline loading and unloading for product during distribution. They also helped protect the products from damage caused in transport. This was a huge step for the shipping industry, but there were still many challenges.

The problem was without standard dimensions, each shipping container required specialized equipment or chassis to move them. This became a problem when containers were distributed around the world to facilities with varying equipment and capabilities. People did not have the right equipment to lift or move the wide array of customized containers.

Slowly, groups began working together to define standards for the shipping industry. Container sizes were standardized into 10-foot increments. Corners of the containers were fitted with universal lifting and lockdown mechanisms, so they could be handled at any port or shipping facility. Standardization provided huge gains in efficiency and reduced costs.

Today, the shipping container industry sings. Standards have defined the size of containers as well as the lifting and lockdown mechanisms. This helps facilitate smooth distribution and product movement around the world. These developments have made the world smaller – and the world economy bigger according to The Box author, Marc Levinson.

The fast-emerging field of personalized medicine needs to define standards for similar reasons. Without these standards, the industry will be limited in how quickly it can scale for global distribution. Freezer manufacturers, logistics companies, and hospitals receiving final patient product all struggle with the impact of slight variations in cassette dimensions. While the variations of cassettes can be measured in millimeters, the impact of not having standards is enormous. What if the cassette you choose requires a larger dry shipper? What if the regional facility does not have the right racking to temporarily store the product until the patient is ready?

While companies like Brooks Life Sciences have decided to engineer to support the current industry leaders researching and developing CAR-T therapies, there is no standard cassette dimension today. If cassettes with larger dimensions are selected in pre-clinical phases, it can have significant impact on logistical efficiencies and costs.

Last, when product is received by the hospital or a third-party logistics hub near the patient, they need to have the right racking to support various cassettes – or spend time (and add risk) by swapping the product to compatible equipment. This could can put product at additional unnecessary risk of bag fractures or unwanted temperature cycling.

In summary, there is significant opportunity to improve efficiencies and reduce costs for products requiring cryogenic handling in cassettes.

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