Biopharmaceutical companies often produce millions of units of bulk biological materials that are then distributed for clinical use. This represents a significant supply chain challenge, as these materials need to be maintained within very specific environmental parameters. Temperature, humidity, and stress during material handling must be tightly controlled to prevent degradation of quality. Large-scale freezing of biologics provides a safe and effective method of storing biological materials, but this approach comes with unique challenges.
Importance of Bulk Production and Transport
Many biotherapeutics are expensive to produce. Manufacturers often produce large quantities of biological materials at once to reduce production costs, allowing them to transfer lower prices on to consumers. However, this approach creates a significant challenge: how to safely and effectively store bulk drug solutions for longer periods of time. The best storage solution must prevent degradation of drug chemicals while making efficient use of space. The majority of drugs are thus maintained at a sub-freezing temperature until they need to be thawed for clinical usage.
Advantages of Freezing Biologics
Freezing biological materials has several advantages over alternative methods of storage. These include:
- Ability to separate production of bulk solutions from creation of the final drug product. Because it is expensive to manufacture many biotherapeutic agents, freezing allows the production of large quantities which can later be produced into final drug materials.
- Slow chemical degradation. Scientists study the kinetics of drug molecular action to determine whether the substance has become degraded. Enzymatic activity and other biological processes are slowed or halted by deep freezing. Thus, maintaining biotherapeutics at sub-freezing temperatures prevents chemical degradation of the drug product.
- Reduced microbial growth. Another threat to the quality of biological materials is the growth of microbial agents. These can compromise the safety and efficacy of the drugs. Most microbes thrive at warmer temperatures. Freezing bulk drug solutions effectively halts the production of microbes that threaten quality.
- Lower transportation stress. Mechanical stress and interaction of chemicals with the surrounding air can affect quality. Freezing prevents mechanical stress during transportation. Furthermore, it reduces the ability of the chemicals to interface with air, which can lead to problematic reactions.
- Cost advantages. Freezing biologics is also a cost-savvy move. Many products can be frozen for relatively long periods of time before undergoing any degradation in quality. Thus, freezing is an acceptable option for low cost, long term storage of biotherapeutics.
Surmounting the Challenges of Freezing Biological Materials
What is frozen eventually must thaw. This is one of the greatest challenges facing the freezing approach to the storage of biologics. It is critical to manage both freezing and thawing parameters to prevent a loss of quality. For example, the amount of time needed to freeze a solution may affect phase separation, creation of ice, crystallization, pH change, solute redistribution, and glass formation. These chemical processes may destabilize the structure of proteins. Protein unfolding, in turn, may cause proteins to aggregate within a solution. These are undesirable outcomes that must be managed.
Similar problems face frozen biologics during the thawing phase of the process. Thawing the product too slowly or too rapidly may cause destabilization of proteins and loss of quality. For biotherapeutic agents that often act within a specific window of concentration, this can be catastrophic.
The industry has developed numerous solutions to address the freeze-thaw cycle problem. Passive cooling systems, such as carboys or bottles, are one method of freezing. Perhaps the more widespread option is use of active systems such as cryovessels. These utilize coolant circulation to actively freeze biological materials at a given rate. Bag freezing systems may also be effective for large-scale freezing efforts.
The use of freezing to store biological materials has numerous advantages, but improper control of the freeze-thaw cycle can dramatically affect product quality. Thus, it is important to choose a storage provider that has the technology needed to freeze and thaw products at the correct rate and temperature. This ensures that, once diluted to therapeutic levels, the drug product maintains its original safety and quality.
The costly nature of irreplaceable samples/cell lines and high value products such as cell-based drugs, and biological active pharmaceutical ingredient (Bio-API) dictates planning for the full continuum of risk. Download your free eBook Defense in Depth: Off-Site Storage for Biological Specimens and Biopharmaceuticals for Risk Mitigation and learn the right questions to ask when choosing an offsite storage facility.