What is freeze-drying?

Freeze-drying is also known as lyophilization. This is a technique used for preservation of perishables such as food, or items which deteriorate if not refrigerated. Freeze-drying can be performed under conditions of decreased temperature as well as low pressure.

Freeze-drying is different to dehydration in the sense that dehydration involves exposure of the material to hot air which absorbs the moisture, leading to dryness. In freeze-drying, the moisture is taken out by placing the material on racks which are exposed to vacuum. In these vacuum conditions, the temperature is lowered to and then slowly raised. This causes the moisture to move from the gaseous state (steam) to solid (frozen). The nutritional value of the material is kept intact.

Freeze dryers use a combination of refrigeration and vacuum pressure to meet the lyophilization needs of a variety of research and manufacturing environments. They are commonly used for culture storage, food and pharmaceutical processing, and material stabilization. With a wide variety of options available, there is much to consider when purchasing a new freeze dryer.

To make sure you get the right system make sure you’ve considered these questions.

1) What type of products are you freeze drying?

Even answered generically, this question provides a great deal of information. Food products are unlikely to contain organic solvents, which often require acrylic parts to be replaced with stainless steel; diagnostic reagents are often processed in very small amounts and therefore may need precooled shelves; injectables will be processed in vials and require stoppering; water-damaged documents will not require inert gas backfilling. Products such as collagens or aerogels which use freeze drying to specify pore size may be interested in control of ice nucleation.

The product type often informs the container type. The most common container types for freeze drying R&D are bulk trays and vials, but microtitre plates, flasks and PCR tubes are also used. Some containers are less ideal for freeze drying: for example, plastic containers have poor thermal conductivity and flasks will not stand on a shelf on their own. However as long as the additional requirements of shelf spacing or cooling time are taken into consideration, even these products can be successfully freeze dried.

2) Is the system for cycle development, formulation development, or both?

It may be you already have formulations that are more-or-less determined, and your freeze dryer will be used for final adjustments, cycle development and quality control. If so it’s possible to be quite specific about the temperature parameters required. However if the formulations are less developed you may want to consider a system with more flexibility to accommodate any changes in thermal characteristics. This may include a lower condenser temperature, larger shelf area, and additional process monitoring systems.

For facilities that are developing large numbers of products, technologies such as SMART Freeze Drying Technology ™ can significantly streamline process development by calculating a trial cycle and automatically fine-tuning it over the course of a few runs (typically just 3).

Note that changes in batch conditions (container size, fill depth, equipment) can all affect the way freeze drying progresses.

3) Do you know your products’ critical temperatures?

The critical temperatures of a product define key processing setpoints: for example, a product must be kept below its collapse temperature throughout primary drying to avoid processing defects. Other critical temperatures may include freezing temperature, glass transitions (a single product may have several), and other frozen-state events.

Not every cycle is developed using knowledge of critical temperatures. Even in those cases where a good cycle has been developed purely by trial-and-error, data about a product’s behaviour may be required for process optimisation, quality control, scale-up and regulatory submissions. If you are uncertain of your products’ thermal profiles, or if your formulations have changed, it’s a good idea to have them characterised. Freeze drying microscopy is the most important analysis and will tell you a product’s collapse temperature. Methods such as DSC, DTA and Impedance Analysis are also invaluable. Choosing an analysis provider who is expert in freeze drying means they will be able to advise you on the implications of the results.

4) Will the system be used for production?

R&D freeze dryers are often built with the level of control and security required for manufacturing and some are used solely for small-scale manufacturing. It’s common for systems of this type to be multipurpose so that product and process development can progress straight to pilot-scale production without delays in sourcing a CMO or additional equipment.

Where the equipment might be used for pilot- or full scale-production, the primary considerations are the batch capacity (shelf area and condenser size), control system security, controlled-environment requirements, and documentation requirements.

Systems used for commercial production will generally need to be validated on installation and the chain of paperwork leading up to construction is often more complex, involving User Requirement Specifications (URS), Functional Description Specification (FDS), Factory Acceptance Testing (FAT), Site Acceptance Testing (SAT) and finally Installation and Operational Qualification (IQ/OQ). Some of these tests cannot be conducted retrospectively so it’s important to make sure they are considered early on.

5) What is the intended throughput?

A poorly specified R&D freeze dryer can cause a bottleneck in development work. It may be useful to consider the required throughput per week or per month and calculate the batch variables from this. Batch size is usually given in terms of volume of product and/or number of a specific type of container (e.g. vials).

The batch parameters will enable the condenser size to be specified, normally given in terms of weight or volume capacity and in a specific time period. The container type and fill depth will enable the required shelf area to be calculated.

Where batch size is being calculated from a throughput requirement, it’s important to factor in not just the duration of the cycle but time for loading/unloading, defrosting, cleaning and maintenance.

If a number of products or formulations are in development, it is worth considering two smaller systems in place of one large freeze dryer, providing flexibility and redundancy.

Applications of Freeze-Drying

The process of freeze-drying can be employed in the following fields

1. Food industry – Food needs to be preserved by freeze-drying for consumption by individuals in the fields of space exploration, hikers, military personnel, as well as the availability of dehydrated foods such as noodles, soups, etc. The most common form of freeze-dried food is instant coffee.

2. Dairy industry – Dairy products which usually required refrigeration were preserved by freeze-drying during World War II. Dairy solids and liquids both can be preserved by this technique, and do not require the use of chemical preservatives. The decreased volume of the product after freeze-drying proves to be an added advantage in the event of transportation of products. Dairy products which can be preserved by freeze-drying include milk, yogurt, ice-cream, cheese, etc. These products can then be supplied to bakeries, dairies, restaurants, etc.

3. Nutraceuticals – In the case of nutraceuticals, the process of freeze-drying used for stabilization as well as increasing the shelf-life of the products. Liquid nutraceuticals are converted to the powder form, which helps in preserving them for a longer time. Nutraceuticals which can be preserved by freeze-drying include seaweeds, aloe vera, tea, etc.

4. Starters and Cultures (edible cultures) – In the case of regular drying methods, the resultant product loses its quality. This might bring about adverse changes in the properties of the product. Products preserved using this technique include probiotics, buttermilk, etc.

5. Pharmaceuticals – Pharmaceutical companies use freeze-drying as a tool to increase the shelf-life of drugs and vaccines. If a liquid drug is converted to its powdered form and stored in a vial, it can be easily reconstituted as necessary. Pharmaceuticals subjected to the freeze-drying process include vaccines, hormones, proteins, plasma, antibiotics, etc.

6. Research – Botanical samples are preserved by freeze-drying to be used for research purposes.Laboratory samples which can be preserved by freeze-drying include active pharmaceuticals, ingredients, pathological samples, microbiological cultures, viruses, bacteria, antibodies, etc.

7. Document Recovery – The process of freeze-drying can be used for recovery and saving of documentation facing damage through fire, floods, etc. Freeze drying using vacuum can be used to restore books damaged by water as well as paper containing water-soluble inks.

8. Floral – The moisture content present in flowers is eliminated through vacuum extraction, followed by freezing at low temperatures. This prevents floral shrinkage, and maintains the structure and quality of flowers.  Flowers which can be preserved using freeze-drying include aster, carnation, daffodil, hyacinth, rose, etc.

9. Taxidermy – Freeze-drying is not an alternative to taxidermy but can be considered as an asset to taxidermy. Animals possessing a large quantity of lipid content need to be processed accordingly in order to achieve optimal quality of freeze-drying. Animals which can be preserved using freeze-drying in taxidermy include birds, fish, dogs, cats, museum specimens, etc.

10. Pet Food – Removal of moisture is necessary for long-term preservation of pet food. However, this removal of moisture can have an adverse impact on the nutrition and quality of the product. Freeze-drying helps in preservation as well as maintenance of product quality. Pet foods which are subjected to freeze-drying can be regarded to be as close to a naturally-occurring diet. These foods can be shaped accordingly for transportation and convenience purposes. Reconstitution of pet food can be done using water, or can be consumed by pets in the powder form.