Hazards freeze drying

While it is necessary to provide adequate precautions to personnel when freeze-drying hazardous products, overcautious risk assessment can result in unnecessary or even impractical working regimes. An example where risk assessment may require modification is where live attenuated vaccines are freeze-dried on an industrial scale, when it may be operationally impossible to handle such strains with the precautions essential when processing virulent strains of that organism. 

Media formulated for freeze-drying hazardous products have to satisfy two quite different criteria which are ... 

Clothing the operator completely in an impervious plastic suit represents the ultimate in personal protection and has the additional merit of isolating the product completely from operator and such suits have been used to maintain sterility during pharmaceutical manufacture. Isolator suits should not be used as the primary means of protecting the operator but must be used only in combination with effective techniques for safely dispensing, handling and freeze-drying hazardous products. 

At first sight, then, complex mechanical setups as we propose for semicon-tinuous or continuous freeze-drying seem susceptible to serious hazards in the sterility control of the operation. However, this is not as dramatic as it looks since the essential part of the process—if not the entire process—is carried out automatically and can be done entirely within a sterile environment by remote control. Indeed, today highly sophisticated automation can be achieved if we resort to the advanced technologies developed for the nuclear industry and profit by the experience of their operators. However, this sophistication will definitely bear on the cost and this can be a serious drawback for conventional low-priced products. 

Drying— removal of solvent or water from a solid or semisolid (sludge) or the removal of solvent from a liquid or suspension— is a very important operation, because water is often the major constituent of waste products, such as sludges. In freeze drying, the solvent usually water, is sublimed from a frozen material. Hazardous-waste solids and sludges are dried to reduce the quantity of waste, to remove solvent or water that might interfere with subsequent treatment processes, and to remove hazardous volatile constituents. 

While the emphasis in this chapter will be to consider hazards when freeze-drying pathogenic micro-organisms or their products, it is important to appreciate that the freeze-drier is an industrial machine and therefore subject to non-biological hazards which will influence safe operation as outlined in Table 10.1. 

Chatigny and Clinker compared common laboratory accidents and showed that exposure to a broken vial of lyophilised bacteria was particularly hazardous. While the precise magnitude of their assessment may be a matter for discussion there is no doubt that handling freeze-dried cultures of pathogens or toxins may constitute a significant hazard. ... 

Product preparation includes sample preparation and dispensing of the formulated product into suitable containers prior to freeze-drying. Dispensing is a particularly hazardous operation and will be discussed in greater detail in section 10.4. 

Table 10.1 Potential non-biological hazards associated with freeze-drying equipment...

Although the shelf-life of a labile bioproduct will be appreciably extended by freeze-drying, stored material will not be immune to thermal decay and it may be necessary to store the freeze-dried product within a refrigerator to ensure maximum stability. For use, the dried product is reconstituted with water or an alternative medium and the hazards associated with both product storage and reconstitution will be addressed in section 10.4. 

Table 10.2 Classification of hazardous agents processed by freeze-drying Group I Low risk...

Although spillages during product dispensing may contribute to ablation, the two hazards are quite different. Ablation can occur in the absence of spillage and will contaminate all internal surfaces of the freeze-drier. As discussed above, ablation is not associated solely with a poorly formulated product but should always be anticipated whenever pathogens or toxins are freeze-dried unless validated physical barriers are interposed between the product and the interior of the freeze-drier. 

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. 

The use of pressurised steam for decontaminating a freeze-drier The advantages of using pressurised steam as outlined above strictly apply only when sterilising freeze-driers prior to processing parenteral products. When it is intended to use pressurised steam to decontaminate a freeze-drier which has been used to dry hazardous materials, a potentially serious disadvantage should be considered related to the need to raise the... 

Breaking points are the availability of the raw materials and primary containers of reliable suppliers, the feasibility of analysis of the drug substance and the preparation and the availability of equipment. As an example, preparation processes such as tableting, freeze-drying or aseptic production are accessible in a few pharmacies. The preparation of oral solids with controlled release is not possible in pharmacies mainly to lacking equipment (fluidised-bed techniques and instrumental analysis, etc). Working with radiopharmaceuticals also requires very specific facilities, as is the case with preparation of solid dosage forms with hazardous substances. 

Categorisation of pharmaceutical preparations (within the field of occupational safety and health seen as mixtures) into hazard categories is relevant because exposure to it can occur in practice. This happens for example when dissolving a mixture of freeze-dried substances or by the crushing of tablets for patients who cannot swallow. 

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