620 Fermentation and Biochemical Engineering Handbook versa. The unit's agitator can resuspend and smooth product cake. After washing the product cake, the filter/dryer can be rotated to facilitate drying The filter dryer should be readily sterilizable and allow continuous flow of product to the next operation. Drying can be done in vacuum dryers, fluid bed ryers, continuous or manual tray dryers; the latter is least preferable Solvent emissions and recovery will be an important consideration for any solvent drying system 6.0 MILLING/BLENDING The dried product is aseptically discharged into suitable bulk contain ers or, alternately, to the milling unit. Bulk containers need to be designed for cleanability/sterilization. Milling and blending can be done as separate steps or in series by feeding the milled product directly to a blender. Mill parts are generally sterilized in place and blenders must be capable of cleaning and terilizing in place. The working size of the blender should dictate batch size for the crystallization process. Blending is normally achieved in a tumbler type blender such as drum, double cone, twin, oracube, or in a stationary shell type blender such as a ribbon or vertical screw mixer. Aseptic filling and sampling of the final bulk container should be part of the design consider ations in order to minimize product exposure. If possible, the final bulk product should be filled into its final marketed container at the same facility as manufactured. However, if the final bulk container must be transported the container must be designed and tested for container-closure integrity and product compatibility. A flow diagram illustrating a typical isolation process for a filter/dryer or spray dryer process is shown in Fig. 2 7.0 BULK FREEZE DRYING A suitably sized solution preparation system similar to that mentioned under the previous sections can be used to provide material for bulk freeze drying. ( Since product solutions can be sterile-filtered directly into the final container, microbial and particulate exposure will be minimized. ) The sterile solution is subdivided into trays and placed into a sterilized freeze dryer Aseptic transfer of sterile product in trays to the freeze dryer must be validated. After tray drying, the sterile product is aseptically transferred through a mill into suitably designed sterile containers. the preparation of sterile bulk material is usually reserved for those cases where the product cannot be isolated by more common and relatively less expensive crystalli zation methods. due to recent advances in this field, a freeze drying process should be considered as a viable option. 11620 Fermentation and Biochemical Engineering Handbook versa. The unit’s agitator can resuspend and smooth product cake. After washing the product cake, the filteddryer can be rotated to facilitate drying. The filter dryer should be readily sterilizable and allow continuous flow of product to the next operation. Drying can be done invacuum dryers, fluid bed dryers, continuous or manual tray dryers; the latter is least preferable. Solvent emissions and recovery will be an important consideration for any solvent drylng system. 6.0 MILLING/BLENDING The dried product is aseptically discharged into suitable bulk contain￾ers or, alternately, to the milling unit. Bulk containers need to be designed for cleanability/sterilization. Milling and blending can be done as separate steps or in series by feeding the milled product directly to a blender. Mill parts are generally sterilized in place and blenders must be capable of cleaning and sterilizing in place. The working size of the blender should dictate batch size for the crystallization process. Blending is normally achieved in a tumbler type blender such as drum, double cone, twin, or a cube, or in a stationary shell type blender such as a ribbon or vertical screw mixer. Aseptic filling and sampling of the final bulk container should be part of the design consider￾ations in order to minimize product exposure. If possible, the final bulk product should be filled into its final marketed container at the same facility as manufactured. However, if the final bulk container must be transported, the container must be designed and tested for container-closure integrity and product compatibility. A flow diagram illustrating atypical isolation process for a filteddryer or spray dryer process is shown in Fig. 2. 7.0 BULK FREEZE DRYING A suitably sized solution preparation system similar to that mentioned under the previous sections can be used to provide material for bulk freeze drying. (Since product solutions can be sterile-filtered directly into the final container, microbial and particulate exposure will be minimized.) The sterile solution is subdivided into trays and placed into a sterilized freeze dryer. Aseptic transfer of sterile product in trays to the freeze dryer must be validated. After tray drying, the sterile product is aseptically transferred through a mill into suitably designed sterile containers. The preparation of sterile bulk material is usually reserved for those cases where the product cannot be isolated by more common and relatively less expensive crystalli￾zation methods. Due to recent advances in this field, a freeze drying process should be considered as a viable option.[’l]