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Unlike compressor-based systems and cryovats, liquid nitrogen freezers safely deliver temperature-controlled freezing down to -160°C in minutes to preserve drug products, active ingredients, and biological samples

For decades, the pharmaceutical industry has relied on compressor-based systems to freeze drug products, active ingredients, vaccines, protein biologics, and biospecimens in all phases from research and development to storage, transport, and manufacturing.

Unfortunately, traditional mechanical freezers are limited in significant aspects. Compressors are known to break down frequently and require constant maintenance. Cooling and electrical requirements are high. These systems also utilize refrigerant, which limits cooling to approximately -100°C and is known to have a negative impact on the environment. Compressor-based systems also take considerable time to reach the desired temperature, which can lead to cryoconcentration, damage protein structures, degrade active ingredients, and reduce potency.

More recently, liquid nitrogen (LN2) cryovats have been utilized for faster freezing at cryogenic temperatures below -150°C. However, because the liquid nitrogen is not contained, there is some risk of exposure for technicians. Controlling temperature in vats is also difficult, even impossible, since there is no safe, reliable means of adjusting the temperature of the LN2 within the vat.

Now a game changing technology in the form of liquid nitrogen cryogenic freezers combines the best features of compressor-based systems and cryovats, but without the limitations.

Liquid nitrogen freezers circulate contained LN2 within their walls for safe, fast freezing down to -160°C. The units provide the convenience of an upright freezer with sophisticated temperature controls. By eliminating the need for compressors, liquid nitrogen freezers require much less maintenance or replacement, less energy, and are more eco-friendly since refrigerant is not required.

“Liquid nitrogen freezers cool faster because LN2 has a boiling point of -196°C, enabling units [using it] to cool to temperatures as low as -196°C. Most refrigerants have boiling points higher than -100°C, making it difficult for compressor-based freezers [using refrigerants] to operate at temperatures below that. Since the LN2 is self-contained, there is no exposure to the user or products,” says Kim Boyce, President of Reflect Scientific, Inc. (symbol: RSCF), an Orem, Utah-based manufacturer that develops and markets innovative, proprietary cryogenic cooling technologies for the pharmaceutical, biotechnology, medical, and transportation markets. The company has more than 30 patents relating to the use of liquid nitrogen with low-temperature freezers, chillers, and refrigerated systems.

According to Boyce, advanced LN2 freezers are available for the pharmaceutical industry in a variety of configurations and models, under the Cryometrix brand.

Upright LN2 freezers

Upright liquid nitrogen freezers provide adjustable temperatures from +20°C to -160°C. This is considerably lower than conventional upright freezer options, enabling significantly faster freeze times.

LN2 freezers minimize the risk of sample warming and quality deterioration due to door open-close events and offer one of the fastest recovery times in the industry. To safeguard sample integrity, state-of-the-art temperature and data logging can be easily accessed, and multiple security levels set. A redundant cooling system and onboard 7-day battery backup further ensure that processes can continue uninterrupted even upon loss of power.

The approach also uses up to 90% less energy than mechanical, compressor-based units, which significantly reduces operating costs. Unlike compressor-based systems, no heat is exhausted to the room, eliminating the need for expensive HVAC systems for cooling. The freezer has a small footprint that suits space-constrained storage environments.

Pharmaceutical Case Use: Biorepositories

In the pharmaceutical and medical industries, liquid nitrogen freezers are utilized as biorepositories for the long-term collection, cataloging, and preservation of biospecimens such as tissue, cells, DNA, protein, blood, plasma, or urine. These biorepositories are essentially “libraries” where biospecimens are stored for clinical or research purposes.

Biorepositories are vital for understanding diseases, genetics, developing prophylactic and therapeutic agents, and monitoring human population health including outcomes related to environmental exposures.

Advanced LN2 blast freezers can reliably lower the temperature of pharmaceutical and biological products to as much as -90°C in minutes with a greatly reduced risk of sample damage and significantly increased production throughput.

As an option, blast freezers can be designed to “do double duty” by rapidly thawing product when required using one machine. This can streamline throughput and eliminate the need for separate freezing and thawing equipment.

Pharmaceutical Case Use: Drug substances, vaccines, protein biologics, blood plasma

LN2 blast freezers are used to slow the rate of active-ingredient degradation of drug substances, vaccines, and protein biologics during storage.

For pharmaceutical research and at blood banks, blast freezers are used to rapidly freeze and store a range of thermally sensitive products such as blood plasma and cryoprecipitate. How quickly various blood plasma products are processed and frozen can affect the value and type of product produced, and even its viability.

Mini LN2 Blast Freezers

As the name indicates, mini LN2 blast freezers are smaller benchtop versions for pharmaceutical use where very quick freezing is necessary in a constrained space. Using only a small amount of LN2 from a portable dewar tank, these systems can cool from 20°C to -80°C in under two minutes. The temperature is adjustable from +40°C to -90°C.

Pharmaceutical Case Use: R&D, limited production

Pharmaceutical manufacturers use mini LN2 blast freezers to rapidly freeze and thaw thermally sensitive materials in the R&D phase for new drugs, vaccines, and biological products. It is important to establish the temperature profile of these materials to determine how products will respond to expected temperature fluctuations during transport, storage, and distribution. The compact units can simplify testing with temperature profile recipes to further expedite R&D, quality control, and even low-volume production.

The pharmaceutical industry has long used conventional compressor-based freezers and cryovats while tolerating the limitations. Now liquid nitrogen freezers are proving to be safer, faster, more reliable, eco-friendly alternatives that enable superior temperature control with less maintenance and energy use.

For more information: call 801-226-4100; email info@cryometrix.com; visit www.cryometrix.com; or write to the Cryometrix brand at Reflect Scientific, Inc., 1266 South 1380 West, Orem, Utah 84058.

Unlike compressor-based systems and cryovats, liquid nitrogen freezers safely deliver temperature-controlled freezing down to -160°C in minutes to preserve drug products, active ingredients and biological samples.

For decades, the pharmaceutical industry has relied on compressor-based systems to freeze drug products, active ingredients, vaccines, protein biologics and biospecimens in all phases from research and development to storage, transport and manufacturing.

Unfortunately, traditional mechanical freezers are limited in significant aspects. Compressors are known to break down frequently and require constant maintenance. Cooling and electrical requirements are high. These systems also utilise refrigerant, which limits cooling to approximately -100°C and is known to have a negative impact on the environment. Compressor-based systems also take considerable time to reach the desired temperature, which can lead to cryoconcentration, damage protein structures, degrade active ingredients and reduce potency.

More recently, liquid nitrogen (LN₂) cryovats have been utilised for faster freezing at cryogenic temperatures below -150°C. However, because the liquid nitrogen is not contained, there is some risk of exposure for technicians. Controlling temperature in vats is also difficult, even impossible, since there is no safe, reliable means of adjusting the temperature of the LN₂ within the vat.

Now, a game-changing technology in the form of liquid nitrogen cryogenic freezers combines the best features of compressor-based systems and cryovats, but without the limitations.

Liquid nitrogen freezers circulate contained LN₂ within their walls for safe, fast freezing down to -160°C. The units provide the convenience of an upright freezer with sophisticated temperature controls. By eliminating the need for compressors, liquid nitrogen freezers require much less maintenance or replacement, use less energy, and are more eco-friendly since refrigerant is not required.

“Liquid nitrogen freezers cool faster because LN₂ has a boiling point of -196°C, enabling units [using it] to cool to temperatures as low as -196°C,” said Kim Boyce, President of Reflect Scientific. “Most refrigerants have boiling points higher than -100°C, making it difficult for compressor-based freezers [using refrigerants] to operate at temperatures below that. Since the LN₂ is self-contained, there is no exposure to the user or products.”

Advanced LN₂ freezers are available for the pharmaceutical industry in a variety of configurations and models, under Reflect Scientific’s Cryometrix brand.

Upright LN₂ freezers

Upright liquid nitrogen freezers provide adjustable temperatures from +20 to -160°C. This is considerably lower than conventional upright freezer options, enabling significantly faster freeze times.

LN₂ freezers minimise the risk of sample warming and quality deterioration due to door open-close events and offer one of the fastest recovery times in the industry. To safeguard sample integrity, state-of-the-art temperature and data logging can be easily accessed, and multiple security levels set. A redundant cooling system and onboard seven-day battery backup further ensure that processes can continue uninterrupted even upon loss of power.

The approach also uses up to 90% less energy than mechanical, compressor-based units, which significantly reduces operating costs. Unlike compressor-based systems, no heat is exhausted to the room, eliminating the need for expensive HVAC systems for cooling. The freezer has a small footprint that suits space-constrained storage environments.

Pharmaceutical use case: biorepositories

In the pharmaceutical and medical industries, liquid nitrogen freezers are utilised as biorepositories for the long-term collection, cataloguing and preservation of biospecimens such as tissue, cells, DNA, protein, blood, plasma or urine. These biorepositories are essentially ‘libraries’ where biospecimens are stored for clinical or research purposes.

Biorepositories are vital for understanding diseases and genetics, developing prophylactic and therapeutic agents, and monitoring human population health including outcomes related to environmental exposures.

LN₂ blast freezers

Advanced LN₂ blast freezers can reliably lower the temperature of pharmaceutical and biological products to as much as -90°C in minutes with a greatly reduced risk of sample damage and significantly increased production throughput.

As an option, blast freezers can be designed to do ‘double duty’ by rapidly thawing product when required using one machine. This can streamline throughput and eliminate the need for separate freezing and thawing equipment.

Pharmaceutical use case: drug substances, vaccines, protein biologics, blood plasma

LN₂ blast freezers are used to slow the rate of active-ingredient degradation of drug substances, vaccines, and protein biologics during storage.

For pharmaceutical research and at blood banks, blast freezers are used to rapidly freeze and store a range of thermally sensitive products such as blood plasma and cryoprecipitate. How quickly various blood plasma products are processed and frozen can affect the value and type of product produced, and even its viability.

Mini LN₂ blast freezers

As the name indicates, mini LN₂ blast freezers are smaller benchtop versions for pharmaceutical use where very quick freezing is necessary in a constrained space. Using only a small amount of LN₂ from a portable dewar tank, these systems can cool from +20 to -80°C in under two minutes. The temperature is adjustable from +40 to -90°C.

Pharmaceutical use case: R&D, limited production

Pharmaceutical manufacturers use mini LN₂ blast freezers to rapidly freeze and thaw thermally sensitive materials in the R&D phase for new drugs, vaccines and biological products. It is important to establish the temperature profile of these materials to determine how products will respond to expected temperature fluctuations during transport, storage and distribution. The compact units can simplify testing with temperature profile recipes to further expedite R&D, quality control and even low-volume production.

The pharmaceutical industry has long used conventional compressor-based freezers and cryovats while tolerating the limitations. Now liquid nitrogen freezers are proving to be safer, faster, more reliable, eco-friendly alternatives that enable superior temperature control with less maintenance and energy use.

*Del Williams is a technical writer based in Torrance, California.

Working with an OEM that offers an experimental test run of your product provides evidence-based research that a freezer fulfills your operational requirements

Pharmaceutical and medical researchers rely on blast freezers to quickly freeze drug products, active ingredients, and biospecimens to extremely low temperatures during R&D storage, transport, or manufacturing.

Today, state-of-the-art liquid nitrogen blast freezers can quick freeze products, ingredients, and specimens to ultra-low temperatures much faster and with greater control than conventional technology. However, verifying that a unit can handle specific products with the necessary speed of cooling, accuracy, and reliability is crucial prior to purchase.

To help researchers considering a blast freezer to verify that a unit meets their requirements before purchase, Reflect Scientific now offers a trial test run of its product with complete documentation of the results.

“With a test run, you can understand the process inputs and outputs required by your product and blast freezer before finalizing a purchase. You can design the test with any process requirements or restraints, and we will provide you with the results,” says Sheldon Larson, Customer/Product Engineer, Cryometrix Freezer and Chiller Products at Reflect Scientific, Inc., an OEM of cryogenic cooling technologies for the pharmaceutical, biotechnology, medical, and transportation markets.

According to Larson, the experimental test run report, conducted on a B-90 Cryometrix blast freezer with thawing capability, can help researchers determine key data such as:

• freeze and thaw times of drug substances or drug substance substitutes;
• estimated liquid nitrogen use during a standard designed batch freeze/thaw cycle; and
• other items specified during the design stage of the experimental run cycle.

The Cryometrix B-90 blast freezer by Reflect Scientific utilizes safely contained liquid nitrogen at -196°C to freeze products with cooled air. The system is designed so there is no contact between the LN2 and the operator or product, which helps to ensure safety. It can cool product inside from 20°C to -90°C in less than 10 minutes. The temperature is adjustable from +40°C to -90°C, with temperature uniformity of ± 3°C throughout.

To ensure product quality, the B-90 provides state-of-the-art temperature and data logging, which can be easily accessed through a touch screen or downloaded to a computer. The latest software upgrade allows up to 250 users and 8 security levels. Managers can easily control who can open the freezer, change the setpoint, and adjust the setting.

The blast freezer also offers optional rapid thawing capability up to 40°C in the same machine. With this option, the end user does not need two separate machines but can perform both rapid freezing and thawing procedures with one unit.

According to Larson, the experimental test run report typically provides a summary of test results for the duration of freeze and/or thaw cycle, LN2 consumption for the test run, any abnormalities in testing, and suggestions for production level runs.

In addition, an outline is provided of how the test was set up. This includes the location of each thermocouple that gathered data, along with photos and video of the set up and test if desired. Raw data files of all sensors used during the test can also be provided as specified in the experimental test run design.

When researchers need to verify that a blast freezer effectively meets their needs prior to finalizing a purchase, selecting an OEM that offers an experimental test run with its product can provide the evidence-based research needed to make a fully informed buying decision.

For more information: call 801-226-4100; email info@cryometrix.com; visit www.cryometrix.com; or write to the Cryometrix brand at Reflect Scientific, Inc., 1266 South 1380 West, Orem, Utah 84058.

By Brian Buntz | January 31, 2023

Reflect Scientific’s Cryometrix T‐160 ultra‐low temperature freezer is designed to be a safer, more reliable and more efficient option for the pharmaceutical and medical industries than cryogenic freezers requiring liquid nitrogen. The refrigerator also replaces the compressor and refrigerant design present in most biorepositories.

The upright liquid nitrogen freezer boasts adjustable temperatures from +20°C to –160°C, providing faster freeze times than traditional upright freezer options. The freezer also offers temperature uniformity of ±7°C, ensuring sample preservation.

Eco‐friendly design and other features

The manufacturer notes that the Cryometrix freezer is eco‐friendly, with a simplified design and minimal moving parts. It says the design supports reliability and lowers maintenance costs. Reflect Scientific also offers a 20‐year warranty on the cooling system.

The freezer minimizes the risk of sample warming and deterioration related to door events. The temperature and data logging can be readily accessed, and multiple security levels can be set for enhanced sample protection. The redundant cooling system and onboard seven‐day battery backup ensure uninterrupted processes even during a power loss.

It also offers automatic tracking of temperature and other data.

Furthermore, the Cryometrix freezer is said to use up to 90% less energy than mechanical, compressor‐based units, lowering operating costs. The freezer also eliminates the need for expensive HVAC systems as it doesn’t emit heat into the room.

The ultra‐low temperature freezer offers a redundant emergency valve for use during a power outage to maintain the temperature in the payload bay.

Compact design

Its compact design is suitable for space‐constrained storage environments.

The ultra‐low temperature freezer measures under 8 ft2.

Reflect Scientific also offers products supporting a range of life‐science applications, including plasma freezing, CAR‐T cell storage, stem cell storage and various cGMP processes.

The company’s blast freezers can quickly freeze and thaw temperature‐sensitive materials during R&D for new

drugs, vaccines and biologics. It also supports temperature profiling, which can shed light on how products will handle temp changes during transport, storage and distribution. Blast freezers also store blood plasma, cryoprecipitate, vaccines and other substances.

About the Author: Brian Buntz

The pharma and biotech editor of WTWH Media, Brian is a veteran journalist with more than 15 years of experience covering an array of life science topics, including clinical trials, drug discovery and development and medical devices. Before coming to WTWH, he served as content director focused on connected devices at Informa. In addition, Brian covered the medical device sector for 10 years at UBM. At Qmed, he overhauled the brand’s news coverage and helped to grow the site’s traffic volume dramatically. He had previously held managing editor roles on two of the company’s medical device technology publications.