Determining Optimum Maintenance Temperature for Advanced Therapies, Part 1

Posted by Dan H. O'Donnell on Nov 15, 2017 10:00:00 AM

Vial Holder Cell Therapy.jpgAs referenced in a previous blog post, understanding the proper method of safely cryopreserving your material is essential, but of equal importance is determining the optimum maintenance temperature. There are many factors that go into selecting a maintenance temperature that need to be weighed against cost, process, and equipment considerations. In this two part blog series, we’ll discuss four areas that need to be understood to determine the optimum maintenance temperature for advanced therapy material.

Volume is perhaps the least complex but most often overlooked variable in temperature selection. While it is true that the smaller the product volume the faster it will thaw and cross the glass transition point, there are other considerations such as the process by which the material will be handled as well as the type of vessel in which it will be stored. Additionally, the temperature of the material impacts the working time, which is not a linear function. In a prior post, my colleague Alex Esmon explained that as the static temperature is lowered, the working time to the breach of the glass transition point increases exponentially. This does not mean that lowering the temperature is necessarily better, as a lower static temperature increases storage cost exponentially.

Handling Processes
It is not unusual for an individual product to be out of a controlled temperature a dozen times or more in its journey from control rate freezer to patient bedside. Consider these potential movements:

  1. Cell Therapy Workflow.jpgControl rate freezer to storage box
  2. Storage box to freezer rack
  3. Freezer rack to freezer
  4. Freezer to packaging and labeling processing
  5. Back to freezer rack
  6. Freezer rack to freezer
  7. Freezer to distribution pick/pack
  8. Pick/pack to distribution rack
  9. Distribution rack to dry shipper
  10. Dry shipper to thaw process
  11. Thaw process to bedside

In each step lies the possibility of breaching the glass transition point and damaging the material.

What is the impact on the therapeutic each time it is out of temperature? The answer lies in evaluating and understanding the time each step takes and the environment (ambient, -140°C CryoCart, in a -80°C freezer, etc.). Time-out-of-temperature profiles need to be developed during the process with consideration of a margin for error. Only through understanding the profiles can the optimum storage temperature be determined. The more steps in a process, the longer the process, and the extremes in temperature differential will indicate the need for a lower static temperature. The actual temperature selected will need to be modified by the volume of each dose.

Stay tuned for the second blog post, which will focus on the final two factors that impact optimum maintenance temperature for advanced therapy material. In the meantime, check out my eBook Commercially Successful Cell Therapies: Navigating the Ultra Cold Chain Distribution Minefield.  It reviews several variables that must be address to ensure you don't inadvertently limit your product's scalability and commercial viability, incur unnecessary costs and complications downstream, or fail to meet FDA criteria for documentation of cold chain requirements.


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