1
Customer issue A customer approached BTL with a product that was being freeze-dried using a cycle borrowed from another product. They were discarding a high percentage of each batch due to defects occurring during freeze- drying. Product characterisation carried out by BTL was able to ascertain: The maximum temperature the product could be freeze-dried at before it would be damaged; What events were occurring in the frozen state that were affecting the freezing stage of the cycle. Product analysis confirmed that the existing freeze drying cycle used process temperatures that were too high for the product. Therefore a new cycle would need to be developed. The critical temperature information discovered by characterisation was used to create a “first approximation cycle” tailored to the needs of the product. In this case annealing was also used to increase the collapse temperature as well as increasing ice crystal size for an improved network structure and better drying. The cycle was studied to assess sublimation cooling verses desired product temperature and tracking of product temperature. Moisture analyses confirmed secondary drying was sufficient, with end product moisture of 1.2%. Modulated DSC of the dried material during the cycle optimisation process confirmed that the secondary drying temperature was suitable. The new cycle developed resulted in a product produced with no defects. A visually acceptable good freeze dried cake was produced. Conclusion The newly developed freeze drying cycle was able process the product with 100% success rate. The cycle was safe, efficient and optimised, greatly minimising cycle time without jeopardising product quality. Cycle Development: Case Study Biopharma Technology Ltd +44 1962 841092 [email protected] www.intelligentfreezedrying.com Temperature Time a b c d e Simplified Chart of Initial BTL Freeze Drying Cycle Shelf temperature Product temperature a: Exothermic event as product freezes b: Annealing step c: Effect of sublimation cooling on product temp d: Product temperature approaches shelf temperature, end of primary drying e: Secondary drying Temperature Time Customer’s existing cycle New shortened cycle End of existing cycle End of new cycle New vs Old Freeze Drying Cycles Examples of various processing defects (left) and successfully processed vials (right)
