Customer issueA customer approached BTL with a product that wasbeing freeze-dried using a cycle borrowed from anotherproduct. They were discarding a high percentage ofeach batch due to defects occurring during freeze-drying.

Product characterisation carried out by BTLwas 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 thatwere affecting the freezing stage of the cycle.

Product analysis confirmed that the existing freezedrying cycle used process temperatures that were toohigh for the product. Therefore a new cycle would needto be developed. The critical temperature informationdiscovered by characterisation was used to create a“first approximation cycle” tailored to the needs of theproduct. In this case annealing was also used toincrease the collapse temperature as well as increasingice crystal size for an improved network structure andbetter drying.

The cycle was studied to assess sublimation coolingverses desired product temperature and tracking ofproduct temperature.

Moisture analyses confirmed secondary drying wassufficient, with end product moisture of 1.2%.

Modulated DSC of the dried material during the cycleoptimisation process confirmed that the secondarydrying temperature was suitable.

The new cycle developed resulted in a product producedwith no defects. A visually acceptable good freeze driedcake was produced.

ConclusionThe newly developed freeze drying cycle was ableprocess the product with 100% success rate. The cyclewas safe, efficient and optimised, greatly minimisingcycle time without jeopardising product quality.

Cycle Development: Case Study

Biopharma Technology Ltd+44 1962 841092btl@biopharma.co.ukwww.intelligentfreezedrying.com

Tem

pera

ture

Timea b c d e

Simplified Chart of Initial BTLFreeze Drying Cycle

Shelf temperatureProduct temperature

a: Exothermic event as product freezesb: Annealing stepc: Effect of sublimation cooling on product tempd: Product temperature approaches shelftemperature, end of primary dryinge: Secondary drying

Tem

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ture

Time

Customer’s existing cycleNew shortened cycleEnd of existing cycleEnd of new cycle

New vs Old FreezeDrying Cycles

Examples of various processing defects (left) andsuccessfully processed vials (right)