Robin Vacha, Senior Vice President, Products at Brooks Life Sciences and David Lewandowski, Global Business Development Manager, Cryo Division at Brooks Life Sciences examine the role of unbroken cold chain in research and development
As COVID-19 vaccine research continues to grow at an unparalleled pace, so does the need for -800 C storage in the biobanking industry. In fact, regulated environments require documentation to support 21-CFR-11 compliance for a world becoming more dependent on storage of irreplaceable biological samples and progressive treatments and vaccines.
This piece discusses the critical role of the unbroken cold chain in research and development, including global vaccine and treatment distribution. Specifically, we’re talking about -800 C automated storage and its importance in the cold chain sequence.
Creating a robust logistics cold chain that can handle the massive responsibility of storing, transporting, and distributing biological samples and the vaccines and treatments that come from them is critical. Failure to store and handle vaccines properly can reduce vaccine potency and result in inadequate immune responses in patients and poor protection against disease. This can cause patients to lose confidence in the vaccine or provider if they require revaccination because the vaccines they received may have been compromised.
Maintaining medication in cold chain post-production is a costly process, according to the National Institutes of Health, accounting for some 80% of the price of vaccinations. In fact, research led by David Kaplan and Jeney Zhang at Tufts University School of Engineering found that failures in the cold chain result in the loss of nearly half of all global vaccines. A finely tuned plan that accounts for every step in the cold chain is key to preventing such disaster.
-800 C is the magic number
With ultra-low freezers, the difference between storing at -700 C and -800 C is often subject to debate. Energy savings come with storing at a higher temp, but it’s not only a matter of savings. Most upright ultra-low temperature freezers are optimised at -860 C and hold better uniformity, so the industry has adopted the -800 C paradigm for storage of biological samples. This also carries over into storage of finished vaccines before transport and distribution.
Ultra-low-800 C freezers are a practical option for storing biological materials over the long term. Ultra-low temperatures prevent degradation of nucleic acids, proteins, endocrine molecules, and many other biological molecules and demonstrate the ability to maintain the viability of numerous biological assays and reagents through long-term storage.
Reinforcing the cold chain
Beyond the ideal temperature for storage, companies need scalable, repeatable, and adaptable processes to support the cold chain and eliminate human error and temperature variances linked to manual methods and mechanical freezers. The move toward automated storage is, therefore, becoming a serious consideration to address cold chain scale-up challenges. Automated -800C storage reinforces the cold chain best practices and creates many other benefits that manual storage can’t touch.
Manual sample storage is not scalable, consistent or repeatable. In fact, before COVID-19, studies estimate that unreproducible research costs scientists in the US $28 billion a year.So, researchers know they can’t make mistakes that impact discovery.
Unlike manual mechanical freezers, some new liquid nitrogen-based automated storage systems provide a consistent temperature – even during sample access – with zero temperature recovery time and fully documented inventory. Process control aspects of automated storage include engineered design to limit ambient exposures of non-targeted samples and enable efficient inventory interactions and data connectivity.
Automated storage also supports accurate inventory data access for extensive visibility and helps maintain SOP compliance. This accuracy and inventory visibility will become the norm as high value advanced therapies scale. LN2-based automated storage systems such as BioStore IIIv, can hold samples longer in emergencies than mechanical freezers by a factor of 16x (96 hours versus 6 hours) and deliver samples in seconds versus minutes. Automated storage systems also use 98% less energy than manual freezers.
What automated storage does for samples
Samples sourced from automated storage do not go through the potential shock of thermal cycling like samples from a manual freezer. During routine access from manual storage, thousands of nearby samples are exposed to ambient temperature for unmonitored durations. This can create a wide swing in temperature between the freezer and the ambient environment which can decrease viability as cells are stressed.
Risk mitigation is another benefit of automated storage. By providing days – not hours of protection, automated freezers store samples 16x longer in emergencies than mechanical freezers.
What automated storage can do for researchers
Automated storage comes with various monitoring systems, much like new cars come with computer modules that tell drivers what needs to be addressed. Temperature alarms with full validation and qualification capabilities are typical in automated freezers.
Additionally, automated systems often come with a software controller to serve as the local LIMS or be integrated with a larger enterprise LIMS solution. As a result, automated storage users are more efficient and accurate in documenting all inventory interactions. And in today’s research and development race for a COVID-19 vaccine and treatment, timing and accuracy are vital to success.
Automated sample retrieval in less than one minute saves time and energy as this approach outperforms manual storage systems and give researchers extensive inventory visibility, supporting 21-CFR-11 compliance.
Exacting logistics support the cold chain
Transporting biological samples must follow a strict chain of custody to preserve maximum viability and function. This is vital for all samples and vaccines – but especially for those that are temperature sensitive.
Whether you are moving a specific collection of biosamples or an entire laboratory, exacting logistics and inventory control must be included as part of an overall chain of custody. This ensures samples arrive at their destination in whole, intact, and unchanged.
Rigorous temperature control of biological samples is crucial to maintain their optimal viability and function. It is therefore imperative to safeguard a continuous, tightly controlled cold chain of custody. Expert cold-chain logistics, seamless cold chain management, and precise documentation sample inventory are necessary to avoid inadvertent loss of valuable materials during transport. Specific technologies help ensure optimal maintenance of the cold chain, and therefore sample integrity, when relocating valuable temperature-sensitive materials.
Most biological materials are extremely temperature-sensitive and must be stored at low temperatures, often in a frozen state. For bacterial, viral, or eukaryotic cell suspensions, exact and reliable maintenance of the appropriate storage temperature is crucial to maintain optimal post-thaw cell viability. Therefore, strict adherence to cold-chain requirements for biosamples is essential for any laboratory or biobank.
Adherence to cold-chain requirements can be challenging, particularly when biosamples must be transported, either from a manufacturing or storage site to the point of care or between research centers. Cold-chain logistics are also essential when an entire laboratory relocates its operations or in emergency situations and proper temperature management during transport of such biological materials can be difficult. Carriage between cities (or countries) can proceed for days. Even short transport processes, such as the relocation of samples between laboratories within the same building, pose temperature stability challenges.
Another important consideration is the relocation of an entire lab or biobank. Failure to provide the correct temperature environment for the entirety of the samples of a laboratory or facility during a move would be catastrophic. This scenario requires specialized trucks or mobile biorepositories, vehicles that are outfitted with 110-V and 220-V electrical systems, alarmed temperature control and temperature monitoring, power generators, and the various electric plug conformations that are common in laboratory environments.
Monitoring systems in these vehicles should conform to the regulations outlined in Title 21 of the Code of Federal Regulations, Part 11, to be able to verify storage temperature(s), an audit trail of the sample, and a full chain-of-custody of actions. Redundancy of power generation is key in these vehicles to ensure maintenance of proper storage conditions for biosamples.
Getting vaccines to the point of use
The Centers for Disease Control and Prevention (CDC) estimates that $300 million of vaccines are destroyed each year due to improper storage, transportation, and distribution. If similar issues impact the supply of novel COVID-19 vaccines, the industry at large could face epic consequences.
As the promise of COVID-19 vaccine development continues to gain traction, an unlikely supply chain management and worldwide delivery powerhouse has emerged. United Parcel Service recently announced plans to build freezer farms capable of storing millions of vials of the vaccine in preparation for the day that vaccine delivery and distribution becomes standard.
Two facilities are under construction in Louisville, Kentucky and Venlo in The Netherlands. Each of these locations, both near UPS air hubs, will house a total of 30 million vials, at temperatures as low as -800 C.
President of UPS Healthcare, Wes Wheeler, shared: “This truly will be a historic supply chain feat to distribute millions, if not billions, of life-saving Covid-19 vaccine vials to far-reaching global populations. Lives will depend on us to get these vaccine deployments right, and we’re well-prepared to support all of these efforts until this pandemic is behind us.”
UPS Healthcare also recognises that time and temperature requirements vary for different vaccines. According to Wheeler, UPS freezer farms will be designed to handle the most exacting specifications.
To ensure no detail will be overlooked, the company has had ongoing conversations with the US Department of Health and Human Services as well as the federal Operation Warp Speed team to plan what will be needed to distribute the vaccine.
The logistical challenge is real. But UPS is committed to moving fragile vials of medicine under exacting conditions and into the hands of doctors and patients around the world. Since the two facilities are close to UPS air cargo hubs, overnight delivery to almost anywhere in the world is certain.
Upholding the cold chain in underprivileged regions
This notion of an unbroken cold chain is especially challenging in low income, rural countries around the world. Consequently, researchers have begun to investigate how sustainable cold-chain delivery systems for a COVID-19 vaccine can be established in resource-limited areas. The World Health Organization estimates that only 10% of healthcare facilities in the poorest countries have reliable electricity. And in some countries, less than five percent of health centers have vaccine-qualified storage.
Professor of Cold Economy at the University of Birmingham, Toby Peters, said: “Universal vaccine access is already a major challenge. With COVID-19, rapid mass immunisation will probably be required. Maintaining a continuous cold chain to rapidly transport and deliver COVID-19 vaccine to all communities, many where electricity supply and cooling infrastructure is often non-existent or unreliable, will be a daunting task. Given most of the technologies deployed today will still be in operation in the next decade, the emergence of sustainable and off-grid cold-chain devices allows us the opportunity to create sustainable solutions for COVID-19 vaccine deployment that also can deliver resilient and sustainable cold-chain systems as a lasting legacy.”
In a discussion for NS Healthcare, Marco Gaudesi, head of GDP and cold chain at Médecins Sans Frontières, and Simon White, director for global quality support at Pfizer, shared lessons learned in protecting the cold chain for low-infrastructure regions and developing countries.
One such lesson is the need to establish concrete quality agreements with partners regardless of location to ensure the right measures are in place for any given route to ensure product quality. When these right measures are NOT in place, according to White, tragedy can strike. The example he cites is delivery of the measles vaccine to Sudan some three years ago. The vaccine was not properly stored, and it killed 15 children.
With numerous supply chains already strained and much of the world laser focused on a COVID-19 vaccine, the ability to deliver stealth results while conforming to quality assurance requirements and good distribution practices in the cold chain is top of mind for everyone involved. Especially those who have been at the forefront of such endeavors who understand that it is a collective truth that vaccines need to undergo the same level of consistency in the cold chain no matter where they are being sent and used.
Maintaining a global cold chain in COVID-19 research and vaccine development
A COVID-19 vaccine is what most of our world needs right now. Getting to that place is going to take a massive amount of collaboration to maintain cold chain between the scientists, manufacturers and downstream stakeholders supporting patients in regions around the globe.
As simplistic as it may sound, the vaccine race figuratively begins and ends with storage.
Procuring samples. STORING them.
Pulling samples for research. STORING them.
Going through clinical trials. STORING a vaccine candidate.
Getting FDA approval. STORING a vaccine.
Getting a vaccine to market. STORING a vaccine for use.
Yes, this is a simplified version of events. But given all that storage and care that must be put into protecting samples to help discover a COVID-19 vaccine or create a lifesaving treatment, is it time to consider the role of an automated -800 C storage solution?
An unbroken cold chain and recorded storage temperature, along with associated equipment and logistics, keeps samples at the desired low-temperature range to support the highest quality and goals for their intended use. Automated storage gives COVID-19 labs the means to maximise sample integrity, manage collections more efficiently – and improve turnaround times when sourcing materials from the freezers.
Today, research groups are often required to demonstrate a consistent and documented cold chain, especially as they strive to create new and life-saving diagnostic and treatment solutions. Automation is – and will continue to be – vital to success.
Main image credit: Martin Robles
David Lewandowski is the Global Business Development Manager, Cryo Division at Brooks Life Sciences where he supports market development activities including the understanding of cryogenic infrastructure strategies to support research, manufacturing and distribution of adoptive therapies. He works with organisations to focus on helping customers implement adaptable, scalable and repeatable processes. Lewandowski spearheaded the development of an internationally-based consensus document on LN2 Based Storage Facilities. Prior to joining Brooks Life Sciences, he held senior business development and sales positions at Cryobiosystem, Genentech and Sanofi.
Robin Vacha is SVP and General Manager, Life Sciences Products Division at Brooks Life Sciences where he is responsible for driving innovation that supports complete sample management solutions for research and drug discovery including compound management, biologics, and gene and cell therapies. For the past six years, Vacha has held senior management positions at Brooks Automation including SVP of Global Manufacturing and Senior Director of Operations. Previous experience includes more than five years at United Technologies, where he served as General Manager and Process Engineering Manager.