Growth in the laboratory freezer market is driven by needs and capabilities: the requirement for consistency in sample protection, monitoring, and storage, and emerging connectivity features that enable remote monitoring and data logging.

Nowhere is this level of care more needed than in drug development, particularly for degradation-prone therapeutic proteins, gene therapies, cell-based treatments, and vaccines.

Why drugs are special

Most drugs are stable for extended periods of time but only if they are stored under the right conditions of humidity, light exposure, and temperature. Biological drugs are particularly prone to degradation resulting from excursions outside of their ideal storage temperatures. As we are learning from experience with RNA-based biologics, including COVID-19 vaccines, excursions below the recommended storage temperature range can be just as harmful to the product as higher temperatures.

Approximately 20% of all pharmaceuticals, and 25% of vaccines, arrive at their points of use degraded due to shipping issues, most notably lack of temperature control. Products arriving in compromised condition are unceremoniously scrapped, leading to billions of dollars in lost revenue per year for manufacturers, and, in too many cases, limited access to crucial medicines.

Experts point to a lack of standardization and adherence to storage protocols, particularly during air transport, as the major culprits.

"The bottom line is that storage temperatures affect product quality," says David Lewandowski, Global Business Development Manager, Cryo Division, at Brooks Life Sciences. "It's a problem with all high-value, small-volume treatments, including vaccines and, lately, cell therapies."

The cost of inconsistency

Not adhering strictly to storage protocols for vaccines affects every aspect of the vaccine value chain: Even the disposal of compromised medications costs money. For vaccines, lost doses delay reaching herd immunity or universal protection for vulnerable demographics, resulting in further economic hardship due to restrictions on human interaction.

Lab managers reading this can rightfully ask what this has to do with research, and the answer is everything. Protocols for product storage are based on experience gained during product development, and best practices there depend on experience during research and discovery, where every sample in every cold storage device becomes its own mini stability study.

The most significant source of temperature variability in research settings are those big communal freezers accessible to all but under the responsibility of none. Anyone who has worked in a lab has seen a coworker go into a freezer to retrieve a sample and search, with the door wide open for many minutes. The really careful ones put your samples on top of ovens, benchtops, or the freezer itself as they search. Sometimes they even remember to return those samples to the deep freeze.

"This affects the temperature of every sample in that freezer," Lewandowski explains. "Just because you see a nice coating of frost on those vials doesn't mean they're at the right temperature. Even if you know exactly where your sample is, opening the door exposes the entire collection to transient warming that can be as high as 30°C."

Not tracking these events can invalidate the process's compliance with Good Laboratory Practices or Good Manufacturing Practices.

Automation to the rescue

The solution, says Lewandowski, is automation. Robot-weary readers may need to be reminded here that automation, while often costing several times as much as standard equipment, typically has a very short payback with an easily demonstrated return on investment.

The critical contribution of automation is always consistency, achieved by standardizing specific steps in a process, carrying them out identically between experiments and within a pre-defined time. Recent reports on the irreproducibility of life science research suggest that the more critical a research project, the more attention should be paid to eliminating variables, for example how often and for how long a sample that should be at -80°C spends at room temperature.

Walk-away time, the benefit that frees workers to engage in more value-added tasks, is not as significant with cold storage as with, say, injecting samples or keeping track of microplates. However, automated cold storage minimizes time spent searching for samples, reduces worker exposure to others' samples, and eliminates the need to defrost the unit. There is simply no way to defrost a large freezer full of samples without unnecessarily exposing all samples to ambient conditions.

Many companies sell automated refrigerators operating at temperatures ranging from above freezing to liquid nitrogen temperatures, and with varying degrees of automation. Lewandowski recommends that purchasers considering automated refrigeration/freezing contemplate the entire range of features before making what will certainly be a serious investment.

  • Capacity: Units should accommodate a range of containers, and be scalable to accommodate growing needs
  • Efficiency: Inventory interactions need to be precise and accurate. Brooks' BioStore™ IIIv, for example, retrieves samples in less than a minute while protecting and tracking every move.
  • Data connectivity: An automated freezer needs to "talk" with supervisory or lab-level software to eliminate transcription errors, record retrieval times accurately, manage inventory, interface with other laboratory equipment, assure sample security, and comply with 21-CFR-11 requirements for regulated industries. This feature alone is worth the price of admission, Lewandowski tells Biocompare.
  • Wide temperature range: Vaccines and advanced therapies require various temperatures depending on the product, shelf-life, and intended use. Collections could have temperature-controlled storage requirements between just below freezing temperature to -190°C.

For example, Brooks' BioStore III LN2 automated freezer accommodates all critical temperature profiles, is accessed via secure login, and includes onboard temperature monitoring with alarms. According to Lewandowski, lab workers interact with BioStore similarly to how they might approach a vending machine but with much higher security and documentation of each transaction.

Selecting a laboratory freezer, especially a large communal unit, has never been easier but the myriad choices involved can cause lab managers to throw their hands up. Our suggestion is to approach these purchases as you would any other: Learn and explore the benefits of automation and connectivity, and think outside the box to include such values as consistency, walk-away time, and automated documentation.