Safe storage of biologics: Requirements & solutions

Safe storage of biologics is key in ensuring the efficacy and safety of pharmaceutical products throughout their lifecycle. As the demand for biopharmaceuticals continues to rise, so does the need for efficient and reliable storage solutions that maintain the integrity of the cold chain. Biologics, including vaccines, monoclonal antibodies, and cell therapies, are often highly temperature-sensitive, requiring precise control to prevent degradation and ensure potency.

In this article, we will discuss essential requirements and innovative solutions for the safe storage of biologics along the cold chain – from ultracold and cryogenic freezers to solutions for safe packaging of biologics.

Temperature control in cold storage

Temperature control plays a pivotal role in the storage of biologics due to the inherent sensitivity of these products to temperature fluctuations. Biologics, such as mRNA vaccines or allogeneic stem cell therapies, often contain delicate molecular structures that can be easily compromised by exposure to inappropriate temperatures.

Maintaining the prescribed temperature range is critical to preserving the stability and efficacy of biologic products. Deviations from the recommended storage conditions can lead to irreversible damage, including denaturation of proteins, loss of biological activity, protein stability, and degradation of nucleic acids. These alterations can not only render the product ineffective, but also pose potential safety risks to patients.

It is the recommended storage temperature that, being specific for each product type, makes cold chain management so complex for pharmaceutical companies and CDMOs. For instance, Fc-fusion proteins have been found to aggregate during long-term storage at -30°C; samples stored at both -70°C and -20°C, on the other hand, remained stable.

Nevertheless, there are some rules of thumb regarding typical storage temperatures for biologics:

• monoclonal antibodies: -80°C
• mRNA: -80°C
• gene therapies: -80°C
• cell therapies: -130°C and lower
• gene-modified cell therapies: lower than -150°C

Furthermore, the temperature sensitivity of biologics extends beyond storage to transportation and handling. Fluctuations in temperature during transit can have detrimental effects on product quality, particularly if the excursion occurs outside the acceptable range.

Combining efficiency and safety

Achieving the delicate equilibrium between efficiency and safety is a balancing act in the storage of biologics. While optimizing storage processes for efficiency is essential to meet production demands and minimize costs, it must not compromise the safety and integrity of biologic products.

Efficiency in storage entails streamlining workflows, maximizing storage capacity, and minimizing downtime. However, these optimizations must not compromise safety measures, such as temperature control, contamination prevention, and product traceability.

By integrating efficient storage practices with advanced systems and robust safety protocols, biopharmaceutical companies can ensure that biologic products are stored in optimal conditions while reducing the risk of product loss or compromise. This holistic approach to storage management not only optimizes efficiency in biomanufacturing, but also safeguards product quality and patient safety throughout the cold chain.^1 2 

Ultra-cold storage for biologics – when refrigeration is not enough

Ultra-cold storage involves temperatures around -80°C, and is crucial for preserving the efficacy and stability of biologics, such as vaccines, cell therapies, and mRNA-based drugs. These delicate biopharmaceuticals often require storage at ultra-low temperatures to prevent degradation and maintain protein stability along with therapeutic properties.

Ultra-low temperature storage can either be necessary

• right after freezing for shipping and long term storage,
• upon arrival at the drug product manufacturing site prior to fill/finish,
• or when buffer, media or intermediate drug substances need to be short- or midterm stored during bioprocessing.

However, achieving and maintaining such extreme temperatures presents several challenges:

• Infrastructure requirements: Ultra-cold storage necessitates specialized freezers with precise temperature control capabilities, which can be expensive to purchase and maintain. Additionally, facilities must have adequate space, power supply, and backup systems to support these freezers – and to scale up capacities if need be. Here, storage density is an essential criterion, as e.g. walk-in freezers come with a large footprint, need specialized infrastructure, and require a considerable amount of energy, while upright storage freezers may be more resource effective.
• Temperature control: Maintaining consistent temperatures throughout the storage period is paramount for ensuring the integrity of biologics. Fluctuations or deviations from the desired temperature range can compromise product quality and efficacy, leading to potential safety concerns.
• Logistical concerns: Transporting biologics to and from ultra-cold storage facilities requires careful planning and coordination to prevent temperature excursions. Any deviation from the recommended temperature range during transit can result in product degradation and loss of potency.

Single Use Support's ultra cold storage RoSS.FRDG addresses these challenges by offering precise temperature control down to -75°C (-103°F), ensuring the integrity of stored biologics. Its modularity allows for tailored shelving systems to accommodate various sizes of bioprocess containers, maximizing storage density and providing efficient storage solutions.

Moreover, its modularity enables easy integration into existing facilities, offering flexibility in storage location and setup. Being compatible not only with RoSS® Shells as a dedicated protective packaging solution further discussed below, but also with all other primary packagings, the RoSS.FRDG provides additional protection for single-use bioprocess containers during storage and transport.
 

Enhanced protection during cold storage and logistics of biologics

Effective protection during biologic storage is crucial for maintaining potency and safety. Temperature fluctuations and environmental factors can compromise their integrity, leading to reduced efficacy or complete loss. Robust protection measures are thus essential.

The RoSS® Shell offers a solution by providing a secure enclosure for single-use bags, shielding biologics during transportation, freeze-thaw cycles, and storage. Its versatility and compatibility with various bag sizes and manufacturers ensure consistent protection from physical stress, which might lead to bag ruptures and product loss.

Moreover, the RoSS® Shell's stackable design optimizes storage space, making it ideal for streamlining cold chain logistics. It represents a significant advancement in biologic protection, offering reliability and efficiency throughout the supply chain.

Putting the puzzle together – platform solutions by Single Use Support

Single Use Support integrates a suite of platform solutions tailored to the various demands of biopharmaceutical production. One of the key elements in the product portfolio is the RoSS.pFTU platform for freeze/thaw processes in the production of biologics, featuring scalable units adaptable to diverse batch sizes and bag types. This system based on plate freezing ensures meticulous control over the process of freezing biologics, safeguarding the integrity of valuable biopharmaceuticals.

Should even lower temperatures be required, Single Use Support also offers RoSS.LN2F – a cryogenic freezer that is able to reach temperatures as low as -170°C in a controlled manner.

Moreover, fluid management solutions for biosimilars and biologics offer unmatched versatility and efficacy, seamlessly fitting into existing manufacturing workflows. With a focus on quality, safety, and scalability, the RoSS.FILL solutions are designed for the fluid transfer of delicate substances.

In order to provide a safe and resource effective storage solution for biologics and biosimilars, Single Use Support has developed the ultra-low temperature freezer RoSS.FRDG, with customizable inner shelving and elevated temperature monitoring. It provides stable temperatures down to -75°C, protecting valuable biopharmaceuticals in different primary packaging solutions and sizes.

With the advanced platform solutions by Single Use Support, pharmaceutical manufacturers can rely on future-proof systems that aid in mastering the complexities in storing valuable biologics safely and with precision.