Safe storage of biologics: Requirements & solutions

Alexander Fuchs | Single Use Support

Alexander Fuchs

May 8, 2024

Table of contents

Show

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.

What’s needed along the cold chain of biologics?

The safe storage of biologics along the cold chain requires meticulous attention to several critical factors to ensure product integrity and efficacy. From temperature control to protection from contamination, various elements must be carefully managed to maintain the quality of biologic products throughout biomanufacturing – all in regard to regulatory compliance.

What makes cold chain management of biologics and biosimilars even more complex is the need for individualized approaches, depending on the very product or intermediate that is currently being processed. Different types of biologics have unique requirements and vulnerabilities – e.g. physical stress, light or oxygen exposure. One of the most common aspects to be considered is temperature, along with bringing efficiency and safety into harmony.

Fridge for laboratory - RoSS.FRIG high density cold storage

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 

Case Study - Reducing Product Loss | Process-independence

With the implementation of RoSS® shells, a multinational CDMO has been able to standardize its fluid management process thanks to the protective shell’s bag-independence, and regardless of size and type of single-use bag used. RoSS – abbreviation for "robust storage and shipping”: • helps to streamline the liquid transfer process and • optimizes each full cold chain management process by enabling full flexibility.1 The CDMO has now planned an extension of their manufacturing site and is searching

Managing the cold chain: The potential of single-use technologies

Effectively managing the cold chain presents significant challenges in the storage and transportation of biologics or biosimilars. However, single-use technologies offer immense potential in addressing these challenges and optimizing cold chain management processes.

In contrast to walk-in freezers and cold rooms, upright ultra-cold storage freezers with a customized inner shelving system allow maximized storage density and space efficiency. Combined with advanced temperature control including digital alarming management as well as long temperature holding in the case of failure, these freezers offer an elevated level of reliability and safety while being energy-effective and user-friendly.

As not only the number of individual freezers, but also their interior can be customized according to specific needs, they are prepared to be used at different scales, making production lines ready for future changes in capacity needs.

storage-biologics

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.
 

RoSS.FRDG-Rendering

RoSS.FRDG | Ultra Cold Storage Freezer

RoSS.FRDG is an ultra cold storage fridge for frozen drug substances in different sizes. The ultra cold freezer keeps the desired set point temperature down to -75°C. RoSS.FRDG offers highest storage density, is fully movable and can be modularly adapted to your individual needs.

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.

Single use bag protection for drug substances in bulk stream with RoSS shell by Single Use Support

RoSS® Shell | Protecting single-use bags

The safest transport solution for all available single-use bioprocess containers. Robust. Scalable. Single-use bag independent.

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.

  1. Freezing of Biologicals Revisited: Scale, Stability, Excipients, and Degradation Stresses, http://dx.doi.org/10.1016/j.xphs.2019.10.062, Published 2019-11-07
  2. Pharmaceutical cold chain management, https://www.susupport.com/knowledge/freeze-thaw/pharmaceutical-cold-chain-management-overview-freezing-ranges, Published 25.07.2022
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

Freezing biologics – best practices

There is more than one way to prepare biologics for long-term storage under temperature-controlled conditions – in this article, we will explore some of the main freezing methods.

Alexander Fuchs | Single Use Support

Alexander Fuchs

May 6, 2024

Read more about Vaccines

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

Vaccines

The development process of biosimilars

The development process of biosimilars slightly differs from the one of their reference biologics. In this article, we will discuss each phase in detail.

micheal-eder

Michael Eder

May 13, 2024