Alternatives in freeze drying

Refrigerants: New ways to the target

How can we slow down and halt climate change? This question only rarely makes it as far as pharmaceutical manufacturing. However, "classic" refrigerants used in freeze-drying systems are harmful to the environment. What is known as the F-gas Regulation set the course for the European Union as early as 2014, and is still impacting the design of freeze-drying plants today. Optima provides solutions.

It is known that refrigerants such as R404A are damaging to the climate. The "Global Warming Potential", or GWP for short, provides information on this. For instance, R404A has been widely used for years, and has a high GWP value of 3922. A generalized ban from 2020 on refilling refrigerants with a GWP in excess of 2,500 recently had additions by way of exceptions that apply to freeze-drying systems, among other things (Annex III dated 1 January 2020). 

Nonetheless, experts anticipate that their output will be reduced, and resources such as R404A will become massively more expensive, because the ban will remain in place for the majority of applications. Aside from considerations regarding climate protection, it will no longer be possible to use these refrigerants in a viable way in the medium to long term, even from an economic point of view.

Important for you
  • For environmental reasons, and in the near future for economic reasons too: Traditional refrigerants will no longer be practical to use in the foreseeable future.
  • Alternative refrigerants are either not 100 % environmentally friendly or are flammable. There are also technical solutions available for flammable agents. These offer a secure long-term outlook.
  • A wide variety of aspects are integrated into the consulting and design process: the cooling capacity required, system efficiency, effects on the sublimation rate and much more.
  • The new refrigeration systems by Optima have a particularly energy-efficient design and achieve the defined temperatures in the ice condenser and in the installation surfaces with extreme precision.
The alternatives

The chemical industry is conducting intensive research on alternatives to climate-damaging refrigerants. It offers innovations - which have all had one major disadvantage to date: In addition to low GWP values, they also have low flammability and are only suitable for low-temperature applications to a limited extent. Climate-neutral gases such as hydrocarbons are also suitable refrigerants. However, in order to be able to use these flammable refrigerants without risk, the freeze-drying systems must be specifically designed. The solution here is a secondary circuit for the ice condenser.

Furthermore, there are non-flammable refrigerants that comply with EU regulations and have a GWP value of less than 2,500. These include R410A which has a GWP of 2088. In all likelihood this will remain available in the medium term, at least for another ten years or so. R448A, which is also non-flammable and is also likely to be available in the longer term, has a GWP value of 1387. These refrigerants represent progress in terms of climate protection, compared to their "predecessors", but they are not a solution, so if you are fully committed to climate protection, there will be no alternative to flammable refrigerants in the foreseeable future.

Advice and planning

In the meantime, there are a number of different ways to provide plant operators with an individually customized solution. Depending on life expectancy and other criteria, it may even make sense to consider retrofitting existing freeze-drying systems. The following overview provides an introduction to the different approaches:

  • LN2 refrigerants: This technically proven solution has been known for years and is future-proof in terms of the F-gas Regulation. The investment costs in relation to the refrigeration system are lower here compared to the following solutions, but the consumption costs increase the more often the system is used. This means that freeze-drying plants with LN2 refrigerants must be adapted to meet the operator's operating scenario. This solution is suitable for new projects. However, with minimal effort, existing plants for climate-damaging refrigerants could also be converted to an LN2 system.
Freeze dryer
New solutions for alternative refrigerants: If these are flammable, specific refrigeration systems are required for freeze-drying. Refrigeration systems from Optima are also particularly energy efficient.
  • For the use of refrigerants which are expected to be available in the medium term, such as R410A, and refrigerants available in the longer term, such as R448A: Both are non-flammable, but neither is completely environmentally friendly: There are two variations that can be considered; direct and indirect cooling of the ice condenser. From a technical point of view, the indirect cooling of the ice condenser makes the system future-proof. Here the refrigeration system is designed to provide indirect cooling of the ice condenser. Flammable refrigerants can also be used at a later date by replacing the refrigeration system.
    It is not yet possible to say whether the classic design where the ice condenser is cooled directly will require future design changes to the ice condenser in order to comply in the long term with the F-gas Regulation. First and foremost, with this solution the investment costs are lower than with the solution referred to above. However, retrofitting could be technically complex or even technically impossible. Should a retrofit of the ice condenser be deemed necessary and technically possible, the total investment will be greater than for indirect cooling of the ice condenser, which will be implemented immediately. The operating costs for both variants are higher (approx. +10 to +30 percent compared to conventional freeze-drying systems
  • Solutions for flammable, environmentally friendly refrigerants: It is still possible that the chemical industry will be able to find the silver bullet, which in this case means refrigerants that are both non-flammable and completely environmentally friendly. For those who do not want to rely on this and who already prefer a comprehensive, future-proof, environmentally friendly variant today, they could design their refrigeration system as a cascade system, for example. In addition, the indirect cooling of the ice condenser must also be carried out here via a second circuit. Investment costs are higher than those for classic freeze-drying plants (up to +40 percent higher). Operating costs are also higher by around 30 percent.
vial with lyophilized content
The F-gas regulation calls for a rethink in designing freeze drying systems.
Lower energy consumption: New refrigeration system

In the design of refrigeration systems, there are variations that can satisfy specific user needs in the most effective way, including the latest innovations. For the first time, Optima is offering refrigeration systems that have been developed in-house and that are specially designed for use with flammable, climate-friendly refrigerants as cascade systems. Another new variant is the Mirai system, which uses air as the "refrigerant".
There are differences in performance and efficiency depending on the system. The cooling capacity for the installation areas and the ice condenser in the air system, for example, is up to 50 kW per module.

The Optima refrigeration system Module 4 delivers up to 37 kW; the Optima Module 5 up to 74 kW per module; both are for flammable refrigerants. The effectiveness of cold generation for primary drying (the proportion of cooling capacity to the power required) also needs to be taken into consideration. Here, compared with other systems, the two Optima modules demonstrate very good results. The investment costs are a significant factor, to say the least.


It is also clear that the new Optima systems' energy consumption, as well as the energy consumed by the air chillers, has been massively reduced by the use of frequency converters. Only the energy that is actually required is consumed here, and this varies significantly depending on the phase of the freeze-drying process. The precision of the temperature reached has also been substantially improved. This is less than ±1 K in the range of the setting plate temperature.

The right technology and good advice are essential

There are other important factors: The refrigerants have an effect on the cooling capacity of the particular technology. Compared to the traditional refrigerant R404A (100 percent), the alternative refrigerants reach values of 64 to 149 percent (both using a reciprocating compressor). For companies who do not shy away from making financial investments, the use of air chillers is an additional option to achieve the required cooling capacity.

Under the F-gas Regulation, new framework conditions apply to the design of freeze-drying systems. Optima addresses this situation with a variety of system concepts. There is no one perfect solution, but with the variants mentioned above, Optima is well prepared for any new situations. Optimal solutions are created by working in close cooperation and in strong consultation with the user.

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