Batch freeze-drying

Continuous freeze drying From the description of batch freeze drying, it can be seen that the utihty requirements vary considerably. During sublimation drying the requirements are 2 to 2.5 times the average requirement. To overcome this peak load and to meet the market request for high unit capacities, continuous freeze dryer designs have been developed. The special features are twofold ... 

Once a suitable strain is available, the prachce is to grow, often ftom a single organism, a sizeable culture which is distributed in small amounts in a large number of ampoules and then stored at 70°C or freeze-dried. This is the seed lot. From this seed lot, one or more ampoules are taken and used as the seed to originate a limited number of batches of vaccine which are first examined exhaustively in the laboratory and then, if found to be satisfactory, tested for safety and efficacy in clinical trials. Satisfactory results in the clinical trials validate the seed lot as the seed from which batches of vaccine for routine use can subsequently be produced. 

Synthetic hydroxyapatite prepared by mixing stoichiometric amounts of aqueous solutions of calcium nitrate and ammonium phosphate was used in this study. The pH of the boiling suspension was maintained at about 10 by flowing a mixture of NH and throughout the precipitation process. The precipitate was repeatedly washed until the conductivity of the supernatant liquid was observed to be constant. The washed sample was freeze-dried and analyzed. An elemental analysis of the batch preparation showed the Ca/P molar to be ratio 1.64, with the predominant impurity being 2... 

We have employed two different protocols for the chemical fractionation of GSE obtained from MegaNatural-AZ based on the amounts needed for bioactivity-based assays. Batches of GSE (50 g) were extracted in acetone/water (7 3) under N2 with mechanical agitation for 12 h. The acetone was removed on a rotary evaporator and the aqueous phase was freeze-dried to yield 48 g of tannin crude extract (TCE). TCE was further fractionated following two different methods. 

The starting material (batch) after appropriate homogenization should be stored in appropriate containers. Later these containers would be distributed to the interested scientists in order to support their measurements. Of course, first, the appropriate containers, in terms of size (large, small), shape (bottle, vial), properties (hard, soft, coloured), material (glass, plastic) have to be selected. Some other important items at this stage are the preparation of the units imder the appropriate conditions (e.g. freeze-dried material tmder low humidity), each unit should contain an appropriate amount of material (depending on the amoimt needed for each measurement and the availability of the material) and the appropriate number of units has to be decided (taking into account the needs for this specific certified reference material). 

Additional supporting documents are also included in the manufacturing records. These may include computerized print-outs from weighing equipment used to dispense chemical raw materials, or recorder charts obtained, e.g. from a freeze-drier upon completion of freeze-drying that batch of product. 

Tomato Tomato is also popular for the expression of biophamaceuti-cals due to the relative ease of processing of the fruit, and the fact that the fruit can be consumed fresh, thus providing stability of the recombinant protein at room temperatures. Tomato fruit has a short shelf life but, alternatively, can be freeze-dried, an inexpensive and well-established technology. Freeze-drying results in concentration of the protein and maintenance of batch consistency. 

Typical lengths of cycles for food stuffs are 5-10 hr, for bacterial pellets 2-20 hr, and for biological fluids 20-50 hr. A production unit with capacity of 500 L may have 75 kW for refrigeration and 50 kW for heating. Conditions for the preparation of freeze dried coffee are preparation of an extract with 20-25% solids, freezing at —25—43°C, sublimation at approx. 200Torr to a final final moisture content of 1-3%, total batch processing time of 6-8 hrs. 

Some freeze-dried antisera are difficult to reconstitute, or occasionally may lose activity. Test a small sample before drying the whole batch. Any cloudiness after reconstitution is denatured lipoprotein, and can be clarified by centrifugation and does not affect antibody binding. 

Mannitol, a frequently used excipient, shows complexity in its application. Yu et al. [1.148] reported the formation of a metastable mannitol hydrate during freeze-drying. The amount of mannitol hydrate varies from vial to vial in one batch. It reduces the... 

It is desirable that the test be performed after steam sterilization but before freeze-drying the next batch, without risking the integrity of the freeze-dryer. 

Organisms which have been freeze-dried under vacuum (see above). Some bacteria, for example, can be lyophilized and stored for months at room temperature. They can then be rehydrated on demand and used to conduct bioassays. In the Microtox test, lyophilized Vibrio fischeri are stored in a freezer at -20° C and will be ready for use until the expiration date, which is provided with each batch of Bacterial Reagent. Volume 1(2,3). 

A total 6.5 g (1 1.55 mmol) of7-[D-a-t-butoxycarbonylamino-a-(p-hydroxyphenyl)acetamido]-3-(l,2,3-triazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid was dissolved in 175 ml (98 to 100% formic acid under anhydrous conditions. The mixture was stirred at room temperature for 2.5 hours. Part of the solution, 125 ml, was evaporated under reduced pressure to an amber oil. The oil was then azeotroped 3 times with 70 ml of toluene under reduced pressure. The residue was suspended in an 80 20 H20-CH30H solution (700 ml) and stirred for 0.5 hour until most of the solid dissolved, then filtered. The filtration was treated with 1.59 of (Darko) charcoal for about 20 minutes. The charcoal was filtered off through a Celite pad. The solution was then freeze-dried in 9 separate 100 ml round bottom flasks. The freeze-dried material weighed 2.415 g. It was recrystallized in batches of 0.200 g as described above to yield a total of 0.923 g 7-[D-a-amino-a-(p-hydroxyphenyl) acetamidol-3-(l,2,3-triazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid. NMR was consistent, indicating the presence of 0.33 mol of CH3OH. 

---