Freeze-drier design

It would be possible to construct a freeze-drier incorporating features designed to minimise the risks of environmental contamination and in 1972 Parker and Smith described the construction of a laboratory drier designed to freeze-dry pathogens.However, economic constraints inevitably result in adapting commercially available freeze-driers to reduce the risks when processing hazardous agents. 

Modifications and adaptations in design are obviously influenced by the scale of operation. For example, in this laboratory, safe processing of small batches of pathogens can be achieved using a modified laboratory freeze-drier which can be sited, operated and decontaminated in a contained area. Clearly when processing several thousand vials it is not possible to move larger industrial machines. 

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Examples in this chapter include sterile crystallization of a labile compound, yield enhancement by crystallization, yield and selectivity enhancement, removal of low-level impurities via crystallization from the melt, crystal formation in vials in a freeze drier, and non-equilibrium resolution of stereoisomers by crystallization. These examples represent unique crystallization processes designed for specific purposes. One lesson to be learned from examination of these nonmainstream applications is that understanding of principles can lead to inventive solutions to problems. For instance, in Examples 11-2 and 11-3, the solubility difference between starting material and desired product is used to optimize the reaction yield/selectivity by crystallizing the product and protecting it from overreaction. 

Practical aspects of the design and operation of freeze-driers and associated equipment... 

As discussed previously, all the internal surfaces of the freeze-drier must be regarded as contaminated after a pathogen or toxin has been processed, and an important feature of design and operation should include the reduction of ablation. Two physical methods have been adopted to reduce this risk ... 

Irrespective of whether the freeze-drier has been fitted with filters, incinerators or other features designed to reduce internal contamination, freeze-driers used to process biohazardous materials must be capable of decontamination at the end of the cycle. As well as protecting personnel and environment from the processed agent, decontamination will prevent cross-contamination from materials previously processed within the freeze-drier. 

Parker, J. and Smith, H.M. (1972). Design and construction of a freeze-drier incorporating improved standards of biological safety, J. Appl. Chem. and Biotechnol., 22, 925-932. 

Although many types of continuous driers are available, the scale of the operation for which they are designed is rarely appropriate to pharmaceutical manufacture. As with most continuous operations, the cost is disproportionately high for small units. Spray and drum driers provide an exception, because residence times in the driers are short and thermal degradation is minimized. Under some conditions, freeze drying may be the only practicable alternative. 

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