Case Study: Using Phase Change Materials for Refrigerated Shipping

Session Outline Project Background PCM Shipper Design PCM Shipper Qualification Lessons Learned 2

Project Background Client has a licensed product Drug Product is shipped frozen from the UK to intermediate cold storage facilities in either Massachusetts or Maryland The Drug Product is then reshipped (still frozen) to an aseptic Fill/Finish facility in Washington state 3

Product Shipping Configuration Configuration Maximum Minimum Description Six 2L plastic bottles approximately 80% full One 2L plastic bottle and one 125 ml bottle; both approximately 80% full 4

Subambient Shipper Configuration Reinforced corrugated cardboard box lined with insulation panels Maximum or Minimum Product Load Configuration Minimum 40 pounds of dry ice 5

Subambient Shipper Requirements Product must remain below -15 C 6

Subambient Shipper Configuration Reinforced corrugated cardboard box lined with insulation panels Maximum or Minimum Product Load Configuration Minimum 40 pounds of dry ice 7

Subambient Shipper Configuration Validation Max and Min Configurations Validated for Summer temperature profile only This may have been a bit unrealistic, as most of the shipping time was in the hold of an airplane at > 20,000 feet (ie, cold) Holdups in Customs were a greater concern 8

Minor Problem There are a lot of Summer (and Winter) temperature profiles available ISTA Summer 7 profile is the most widely accepted, but it s not an industry consensus Be prepared to defend whatever profile you decide to use 9

Key Learning Point The profile you decide to use is less important that your confidence in defending your decision to use it 10

Product CQA Shipping Related Problem The Drug Substance was routinely coming in low in ph at the aseptic Fill/Finish CMO It occasionally failed this ph specification (low) Enough to cause an investigation to be launched These ph failures represented a six figure financial hit each time it happened 11

Investigation Conclusions The sublimating dry ice was being absorbed by the Drug Substance, which depressed its ph A torque specification was put in place for the bottle cap The DS ph was still low, but in spec 12

Business Decision Design and Qualify a new subambient shipper that did not use dry ice 13

Phase Change Materials The State of the Art has advanced to the point that you can pretty much pick your Phase Change temperature 14

PCM Limitations (compared to Dry Ice) They re more expensive They re bigger and heavier They have limited thermal capacity 15

PCM Advantages (compared to Dry Ice) They don t offgas CO 2 They re reusable They MAY be greener Which is a very subjective assessment 16

Subambient Shipper Redesign Calculated the heat of sublimation of 40 pounds of dry ice 10,360 KJ Calculated the equivalent amount of -32 C PCM required to equal this heat capacity 94 pounds, not including the packaging This would have required a pallet and forklift 17

Subambient Shipper Redesign Reviewed standard PCM Shipper configurations available 1. -25 C 2. -40 C 3. -80 C Options 2 and 3 are much more expensive and complicated to implement 18

Subambient Shipper Logistics Original design (insulated corrugated box with insulated panels and dry ice) isn t worth the expense of reclaiming PCM Shippers are 19

Subambient Shipper Logistics There are Shipping companies that will provide preconditioned PCM shipping containers at an agreed upon time and place For a (not insignificant) price They will also retrieve them You have to tell them to do so 20

PCM Shipper Qualification Prepped 3X Max/Min configurations in a -20 C freezer for 4+ days This was specified in the client s Shipping SOP Placed 3X Max/Min configurations into preconditioned PCM Shippers Datalogger TCs were placed onto each Drug Substance bottle Filled remaining space with insulation (bubble wrap) 21

PCM Shipper Qualification Assembled Load Configurations with TCs into preconditioned PCM shipper in a -20 C walk-in freezer These are very, very cold Plan to go to sleep early that night 22

PCM Shipper Qualification Exposed Max and Min Configurations to 120 hours of ISC Summer Gold temperature profile Selected as it had three 40 C excursions This may have been more challenging than necessary Plan was to test until failure 23

PCM Shipper Qualification Results Min loads met Acceptance Criteria Temperatures < -15 C for 72 hours Max Loads did not meet Acceptance Criteria Temperatures < -15 C for 65 hours 24

PCM Shipper Qualification Data Analysis Min Loads had significantly more insulation (bubble wrap) than Max Loads Proper insulation matters A LOT We re fighting physics 25

PCM Shipper Qualification Observations Bubble wrap is great Cheap, readily available, easy to use The smaller (~1/4 inch) bubbles are better than the larger (~1 inch) bubbles Lots of smaller partitions are better than fewer larger partitions 26

PCM Shipper Qualification Lessons Learned Dry Ice is better, lighter and cheaper PCMs avoid CO 2 absorption Know why you re making the change before you do it 27

Questions? Feel free to contact me at: yeaton@atlanticvalidation.com 28