Cold Chain Logistics – One-Size-Fits-All?

Approved biotherapeutics are the successful outcome of a complex – and often arduous -process, requiring significant expense, time, and effort.  To ensure they are protected, biologics must be handled carefully at all stages of their life cycle. 

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Manufacturers often freeze their materials during storage and transport, especially when dealing with sensitive biotherapeutics. Frozen storage supports more complex manufacturing by allowing longer hold times between process steps. Freezing also maintains product quality by increasing stability, reducing opportunities for contamination, and limiting environmental fluctuations.

A robust frozen supply chain is characterized by the efficient transport of drug substances in secure containers under stable conditions. Unfortunately, flaws in the supply chain can lead to significant delays and losses.

The design and implementation of an efficient frozen storage | transport system – including selecting the best containers, freezers, controlled-rate technology, and logistical framework – is highly context-dependent and driven by various organizational and operational pressures. 

As outlined in our recently published White Paper,  three central drivers of platform selection in the cold chain are:

• The nature of the biologic
• The developmental stage of the product | organization
• The facility operations. 

Below, we explore these drivers in more detail and offer suggestions for optimizing the biopharmaceutical cold chain.

    White Paper: Managing Frozen Transfer Logistics in the Biopharma Cold Chain

Drivers Influencing Cold Chain Logistics

Nature of the Biologic
The continuing development of new drug modalities has driven the emergence of a diverse portfolio of biotherapeutics. Biologics such as cells, proteins, and nucleic acids all have distinct chemical and functional characteristics. Their unique features require individual production, transport, and storage conditions, each with significant consequences for cold chain management. 

For example, whereas proteins typically require cold storage and transport at around -20°C, cells are typically maintained at ultra-low temperatures (< -135°C). Different biologics also differ in their sensitivity to cooling speed and the effects of cryoconcentration; controlled-rate freezing and monitoring are sometimes necessary to maintain the critical quality attributes (CQAs) of the drug product and qualify materials with reliable data. 

Developmental Stage
During the early development of a new biopharmaceutical, time-to-market | clinic and risk management are key aspects of decision-making. End-to-end frozen transport platforms that can be easily integrated into the production process simplify operations and save time. Any new solutions would ideally be compatible with the existing infrastructure, removing the need to implement new instruments and train staff to operate them.

Solutions that reliably support operations at different scales will enable a rapid transition to manufacturing at larger volumes. Comprehensive and scalable systems - such as the Celsius^® CFT platform - simplify cold chain logistics and promote consistency throughout process development and increasing production capacity.

During commercial manufacturing - once a facility has established its production pipelines - cold chain decision-making is primarily influenced by the process parameters. Flexible solutions that fit into existing manufacturing set-ups are most desirable. In some cases, manufacturers may be able to invest in the latest technologies for controlled-rate freeze | thaw, automation, and tracking to ensure robustness in their frozen logistics. 

Facility Operations
It is essential to keep in mind that biopharmaceutical companies do not necessarily fit into defined molds of operational style, production capacity, or developmental stage. However, there are some general trends in their typical operations which might help guide them towards optimal solutions.  

Small start-ups:

• Likely to be particularly influenced by cost
• Might seek freeze | thaw solutions with the lowest expense or choose to adapt their existing platforms
• Often outsource some aspects of their operations to external organizations, requiring scalable platforms to support frozen transport between manufacturing sites.

Larger commercial manufacturers:

• Typically driven by optimizing the efficiency of their production process
• Needs will include managing the storage and shipping of large volumes at significant throughput.

Contract manufacturing organizations (CMOs):

• Likely to carry out diverse projects for different clients
• Require flexible solutions that can adapt to a variety of platforms and product types to maximize their service offerings.

Explore New Decision-Making Strategies

Designing and establishing a robust cold chain is critical, as failures that compromise the integrity of the product are incredibly costly. Each biologic, facility, and process requires unique solutions for freezing; no single strategy will satisfy every organization's needs.

Keeping product security at the center, careful consideration of the needs and drivers for each application will ensure you select the best solution for your product, process, and facility. 

Examine our decision-making framework and discover more solutions for frozen transport in our White Paper. 

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    Evaluating Freeze | Thaw Processes in Drug Manufacturing

More Information:

  Frozen Storage and Shipping
  Celsius^®️ CFT - A Robust and Reliable Platform for cGMP Manufacturing
  Celisus^®️ FFT - Robust Freeze Containers for a More Reliable Cold Chain
  Celsius^®️ FFTp - Compact SU Containers Perfect for Horizontal Plate Freezers