Five questions to ask when sourcing an R&D freeze dryer

by in Uncategorized

May 2015

Freeze dryers can be complicated pieces of specialised equipment, with controlled heating, cooling and vacuum interacting with each other to provide the best drying conditions. They are used for many different types of product and there are therefore a variety of different types of system with hundreds of options to enable them to suit the requirements of different industries and applications.

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

  1. What type of products are you freeze drying?

Various product formats

Many types of product are routinely freeze dried: foods, drinks, and pharmaceuticals

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.

  1. 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.

  1. Do you know your products’ critical temperatures?

Lyostat4LED_analysis

Freeze drying microscopy is used to determine the product’s collapse temperature.

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.

  1. 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.

  1. What is the intended throughput?

Vials on shelf closeup

Vials loaded into a freeze dryer.

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.

Your freeze drying experts

Biopharma Process Systems is your one-stop-shop for freeze drying. As well as a range of freeze dryers that extends from the bench to the plant room, we also provide equipment maintenance and validation services, product and process development, training and analytical equipment. Contact us now to discuss your requirements.

 

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