Ultra-low-temperature (ULT) storage of vaccines

Alexander Fuchs | Single Use Support

Alexander Fuchs

December 11, 2023

Table of contents

Show

Ultra low temperature (ULT) storage emerges as a solid rock to safeguard the cold chain. Despite challenges, ultra-cold storage's benefits, from efficient manufacturing to prolonged shelf-life to global reach, revolutionize vaccine management.

Discover cutting-edge technologies, the role of controlled freezing, and Single Use Support's solution for vaccine manufacturing and long-term storage of vaccines.

What is ultra low temperature storage?

Ultra Low Temperature (ULT) storage is a specialized form of storage that involves maintaining extremely cold temperatures, typically below -60°C (-76°F) and reaching as low as -80°C (-112°F) or even cryogenic temperatures.

This storage method is crucial for preserving the integrity and efficacy of sensitive biological materials, such as vaccines, by slowing down biological and chemical processes.

ultra-low-temperature-storage-vaccine

Why ultra low temperature storage for vaccines?

Vaccines contain components that are susceptible to degradation when exposed to higher temperatures. Exposure at higher temperatures can lead to denaturation of proteins, loss of potency, and reduced effectiveness. Ultra low temperature storage prevents such undesirable outcomes and maintains the vaccine's ability to confer immunity.

Some key components that are particularly sensitive to degradation include:

Proteins:
Many vaccines contain proteins, such as antigens or adjuvants, which are crucial for triggering an immune response. Exposure to elevated temperatures might lead to protein denaturation, rendering them ineffective.1

Nucleic Acids:
Certain vaccines, especially those based on nucleic acid platforms like mRNA vaccines, carry genetic information. High temperatures can degrade the nucleic acids, affecting the vaccine's ability to instruct cells to produce the desired immune response.2

Enzymes:
Some vaccines include enzymes that play a role in the formulation or activation of the vaccine. Exposure to higher temperatures can compromise the activity of these enzymes, impacting the vaccine's efficacy.

Preservatives and Stabilizers:
To enhance shelf life and stability, vaccines often contain preservatives and stabilizers. Examples include thimerosal, formaldehyde, and phenol. Unlike the other vaccine components, these additives do not necessarily require ultra-low-temperature storage. Elevated temperatures may still impact their effectiveness.1 2 3 4 

Managing Vaccine Temperature Sensitivity: Which Ones Require Special Care?

Maintaining the correct temperature for vaccines is crucial to preserving their effectiveness, as many are sensitive to both freezing and overheating. Vaccines like inactivated influenza and inactivated polio (IPV) are highly susceptible to damage from extreme temperatures, necessitating meticulous handling and storage. Similarly, rotavirus vaccines are highly sensitive to heat and must be kept within strict temperature parameters.  Technologies, such as the RoSS.pFTU for controlled freezing and the RoSS.FRDG for ultra-cold storage, are essential to ensure these sensitive vaccines remain potent and safe for administration.5 

Ultra-low temperature technologies

What is essential for the ultra-cold storage of vaccines? A controlled freezing process reaching temperatures as low as -80°C (-112°F) or even cryogenic levels, along with long-term ultra-cold storage solutions such as an ultra-cold storage device. This chapter introduces best-practice solutions in controlled freezing of vaccines and ultra-low-temperature storage, as well as comparing conventional freezers with the ultra-cold storage solution provided by Single Use Support.

Read more: Advanced cold chain solutions for vaccine development

Freezing of vaccines

Freezing drug substances is not merely a procedural step; it's a strategic move to guarantee the stability and quality of the biologics. Beyond compliance with legal regulations for safe handling, this process allows the safe transport and storage of large vaccine volumes or their components until they are needed in the right place, mitigating the risk of structural changes and damage during transportation.

Controlled freezing of vaccines emerges as a crucial practice for ensuring both efficacy and product quality. A best practice approach involves the implementation of a plate-based freezing concept.

The choice of freeze and thaw rates becomes pivotal, with faster freezing rates demonstrating lower levels of cryoconcentration and higher protein stability—an essential factor for the efficacy of vaccines. Traditional freezers, with slow and uncontrolled freezing rates, present challenges for vaccine storage. The adoption of a plate-based controlled freeze and thaw platform addresses these challenges, ensuring homogeneity and product viability in the freezing process. 
 

Whitepaper: How Controlled & Scalable Freezing Becomes Reality

Scalability around freezing means the ability to guarantee constant freezing kinetics on proteins (biopharmaceutical molecules) in all scales, filling volumes and loading scenarios. This guide covers how to achieve scalable freezing & thawing of biopharmaceuticals by showing What is scalability? Setup for controlled icefront growth speed Scalability results Outcomes

Ultra-low temperature storage

Maintaining the low temperature of frozen vaccines is crucial throughout every stage of the supply chain, including development, manufacturing, distribution, and administration at vaccination sites. The continuous cold chain relies on ultra-cold storage freezers or storage equipment, available in various sizes. Single Use Support's solution stands out as an efficient and precisely controllable option for this purpose.

Used across the biopharma industry, from laboratories to biopharmaceutical companies, RoSS.FRDG caters to various needs in cold chain storage. Its modular interior and thus its scalability, stackability, and high storage density make it a flexible solution adaptable to processes ranging from lab-scale studies to bulk production and storage of biopharmaceuticals.

The ultra low temperature storage stands out with its impressive -80°C (-112°F) temperature maintenance, creating an ideal ultra-cold environment for vaccines. The freezer's portability ensures flexibility in-plant, enabling seamless transitions between deep-freezing and subsequent processes like shipping or thawing.

Advantages over conventional solutions include reliable air temperature uniformity, exceptional storage density, cost-effectiveness, and GMP-compliant digital alarm management, ensuring the safety of stored vaccines by promptly alerting operators to temperature deviations.

The significance of temperature monitoring cannot be overstated, ensuring vaccines bask consistently within the required temperature range. Three types of monitoring are necessary to control an efficient and safe cold-chain during vaccine development.

Continuous Monitoring
Real-time vigilance characterizes continuous monitoring systems. Operators are promptly alerted to any deviations from the coveted temperature range, ensuring proactive intervention.

Data Logging
The narrative unfolds over time with data logging, where temperature data is recorded. This historical perspective allows for retrospective analysis, fostering quality assurance.

Remote Monitoring
This innovation enables the monitoring and control of storage conditions from a distance, amplifying overall system efficiency.

RoSS.FRDG-Rendering

RoSS.FRDG | Ultracold Storage Freezer

RoSS.FRDG is an ultracold storage fridge for frozen drug substances in different sizes. The ultracold freezer keeps the desired set point temperature down to -80°C/-112°F. RoSS.FRDG offers highest storage density, is fully movable and can be modularly adapted to your individual needs.

Temperature monitoring

The significance of temperature monitoring cannot be overstated, ensuring vaccines bask consistently within the required temperature range. Three types of monitoring are necessary to control an efficient and safe cold-chain during vaccine development.

Continuous Monitoring
Real-time vigilance characterizes continuous monitoring systems. Operators are promptly alerted to any deviations from the coveted temperature range, ensuring proactive intervention.

Data Logging
The narrative unfolds over time with data logging, where temperature data is recorded. This historical perspective allows for retrospective analysis, fostering quality assurance.

Remote Monitoring
This innovation enables the monitoring and control of storage conditions from a distance, amplifying overall system efficiency.

RoSS.FRDG_Cold Storage of Biopharmaceuticals

Conclusion

As we move forward, continued research and innovation in ULT storage provides the potential to tackle present obstacles like the energy usage and infrastructure needs, further enhancing the cold chain.

The ultra-cold storage solution RoSS.FRDG, offered by Single Use Support provides a practical and energy-saving option. This solution impresses with its impressive storage density, enabling more space utilization, while delivering a compact and mobile in-plant design. RoSS.FRDG is a top choice for vaccine manufacturers, distributors as well as laboratories.

With continuous improvements, ULT storage is poised to play a central role in the evolving landscape of biologics, leading to improved worldwide health results and aiding in the battle against infectious diseases.

eBook: Filling Gaps in Managing Large Volumes of Biologics

Aseptic aliquotation and cryopreservation of drug substances are crucial process steps in bioprocessing. Even though they’re not in the spotlight of biomanufacturing. In drug development and drug delivery, biologics must be transferred at numerous occasions. Along the journey of monoclonal antibodies, vaccines and more, the drug substance passes lots of process steps where liquid transfer is required. This is relevant for the transitions between upstream processing, downstream processing and fill & finish, but also within these manufacturing milestones. The market of fluid & cold chain management has great growth potential and is on its way to professionalization and industrialization. To meet the challenges of manufacturing drug substances, Single Use Support helps manufacturers and CDMOs to advance their fluid & cold chain management process to achieve a secure and efficient process for liquids on the basis of single-use bags.
  1. Vaccine ingredients, https://vaccineknowledge.ox.ac.uk/vaccine-ingredients#Growing-the-active-ingredients, Published 26.05.2022
  2. What are nucleic acid vaccines and how could they be used against COVID-19?, https://www.gavi.org/vaccineswork/what-are-nucleic-acid-vaccines-and-how-could-they-be-used-against-covid-19, Published 23.12.2020
  3. Vaccine Ingredients, https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-ingredients, Published 18.07.2023
  4. Vaccine Safety – Ingredients, https://www.canr.msu.edu/news/vaccine-safety-ingredients, Published 18.01.2021
  5. Temperature Sensitivity of Vaccines, https://cdn.who.int/media/docs/default-source/immunization/supply-chain/temperature-sensitivity-of-vaccines.pdf, Published 03.2014
Alexander Fuchs | Single Use Support

Alexander Fuchs

Head of Product Line Management

Alexander is Head of Product Line Management. He owns a wide range of experience and knowledge in various and different industries such as jewellery, manufacturing industry and biopharma, and multiple areas of activities due to his highly technical education and intensive insights. 

Passionate for Automation, Engineering and Process Management Alexander contributes to the innovative focus of advancing cold chain management within the biopharmaceutical industry. 

More from Alexander Fuchs

Vaccines

Freeze thaw processes in biosimilar production

Freezing and thawing are essential steps in the cold chain management of biosimilars. With several methods eligible, we have chosen some prominent ones, explaining their advantages, limitations, and our preferred choices.

Alexander Fuchs | Single Use Support

Alexander Fuchs

May 8, 2024

Vaccines

Safe storage of biologics: Requirements & solutions

Once biologics are produced, they need to be stored for shorter or longer periods of time, with dedicated storage requirements to be met. Here, we will uncover these requirements, along with solutions to fulfill them.

Alexander Fuchs | Single Use Support

Alexander Fuchs

May 8, 2024

Read more about Vaccines

Single-use Consumables

Dual Sourcing: Strengthening the Pharmaceutical Supply Chain for Single-Use Assemblies

Dual sourcing strategies select suppliers that can meet quality standards, desired delivery times, and overall price expectations. Vendor-agnostic integrators, like Single Use Support, help provide customized single-use systems tailored to specific client needs. This allows them to select the best components and materials from multiple sources, ensuring compatibility and functionality.

1640281789974

David Seifert

October 28, 2024

Vaccines

Fluid management solutions for biosimilar production

In biosimilar production, fluid management takes on an overarching role, as it is encountered at several manufacturing steps. This is all the more reason to deal with efficiency in fluid management – which we will do in this article.

BRMO

Brian Moloney

May 14, 2024

Vaccines

Challenges in manufacturing biosimilars

The manufacturing process of biosimilars is a complex endeavor, accompanied by several challenges. We will discuss some of the biggest hurdles in this article, along with solutions to overcome them.

BRMO

Brian Moloney

May 14, 2024

Vaccines

How to optimize biomanufacturing efficiency

There are several parameters to be considered in the attempt to maximize efficiency in biomanufacturing. In this article, we will discuss different areas that have an impact on process efficiency, including ways to improve them.

michael-muehlegger

Michael Mühlegger

May 13, 2024