Top Considerations to Meet FDA Requirements for Packaging Cryogenically Frozen Advanced Therapies

Posted by Abdul Ally on May 17, 2017 10:06:55 AM

Celltherapy_packagingcryo.jpgUS Food and Drug Administration (FDA) requirements specify that packaging and distribution systems must protect the agent from contamination and damage. In distributing cryogenically frozen advanced therapies, this includes protection from temperature shock.

Packaging and shipper rack design can play a significant part in either maintaining or interfering with correct handling and temperature requirements, in addition to adding inefficiencies. Consider the following issues when planning packaging and distribution:

  1. The container material. The traditional box that works well for ambient and refrigerated therapies needs to be evaluated at cryogenic temperatures.
  2. The container shape. Wrapping labels around the corners of a rectangular container while wearing protective gloves and keeping the box and label inside a CryoCart can be challenging and time-consuming. Given the amount of information required on the label, are the container and its shape optimal? How many containers are expected to be shipped in a single dry shipper?  
  3. The container closure. Folding and closing the lid on a small box is easy at room temperature. However, this is not so easy while wearing bulky, loose-fitting insulated gloves and standing over a CryoCart. Test and experiment with lids that are easy to handle with protective gloves in a cryogenic environment.
  4. Tamper-evident packaging or containers. The options for cryogenically frozen materials differ from those available at less extreme temperatures.
  5. The label stock.  Will the label wrap around and adhere when applied to a -150°C container? How easy is it to apply with bulky, insulated gloves in a vapor phase environment?  What about technicians who are left-handed?
  6. The shipper rack. Once the product is packaged, labeled, and ready to ship, it has to be secured in a cryo-stable frame, or rack, that is then inserted into the cylindrical sleeve of a LN2 dry shipper. This is a critical element of the process: can the product container be efficiently placed into and removed from the rack while wearing personal protective equipment (PPE)?
  7. AdvancedTherapyRacks.jpgStandard vs. custom rack. Can the product containers not only be efficiently loaded in the rack, but also individually secured? Most standard racks must be completely filled, and then all the compartments are secured at once with a single wire retainer. The wire retainer may not be an issue when shipping out the product, but can create retrieval issues for clinical site staff. Custom-sized racks with individually secured compartments are often the best solution, but add time and cost.
  8. Is it easy to install the rack in the cylinder? The loaded rack must quickly and easily transfer into the dry shipper cylinder. The transfer must be quickly and efficiently accomplished by a technician wearing bulky gloves, and by technicians who are left-handed as well as right-handed.
  9. Do all these steps work efficiently in reverse when performed by clinical site staff? To retrieve a single dose, does the rack have to be fully removed from the shipper so the wire retainer can be pulled out? If this is the case, then every time one dose is retrieved from the shipper, the remaining doses are subject to temperature shock. When the target dose is removed, can others fall out? Should this happen, the result is additional time out of temperature and additional temperature shock.  

Within our operations at Fisher BioServices, the packaging and loading of a dry shipper is performed by trained technicians, who are experienced in using bulky insulated gloves and a face mask and working over a LN2 cart. However, the retrieval, handling, and preparation for administration are performed by clinical site staff members, who may not be as accustomed to the use of gloves, mask, or the general process. And few people, including clinical site staff, are aware of how quickly a small volume of cryogenically frozen material will warm and thaw when exposed to ambient temperatures.

Strategically designed packaging and rack systems, accompanied by a clearly written SOP, will ensure temperature-compliant handling, protect the integrity of the product and the patients who receive it, as well as meet FDA requirements.

An invaluable tool in the quest to move material in a safe and effective manner is the dry shipper and its counterpart, the data logger. To learn more, download your free InfoPoster on the 10 Things You Should Know About Dry Shippers Before Shipping High Value Biologics.


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