BioPharm International spoke with Jamie Chasteen, manager of new product development at Cold Chain Technologies, and Rebecca E. Gentile, senior specialist, quality vaccine and biological stability at Merck & Co. about the challenges manufacturers experience when managing the cold chain for biopharmaceuticals and what advances in cold-chain technologies are helping to combat these challenges.
BioPharm: What top challenges do biopharmaceutical companies face when managing the cold chain for biopharmaceuticals?
Gentile (Merck & Co.): A top challenge to managing the cold chain for biopharmaceuticals during distribution is temperature excursions, which can affect the safety and efficacy of the product. Reducing or eliminating temperature excursions during shipping is an important task. Clinical-trial material is shipped to multiple locations, typically in smaller packages, so ensuring that the appropriate packaging solution is being used to maintain the necessary temperature ranges is crucial. For commercial supply, it is crucial to understand the typical shipping lanes and what temperature exposures the product might encounter, work with partners to design and qualify appropriate shipping packages, and work with shipping partners to minimize delays and other potential points of temperature excursions.
Particularly for commercial product, designing the Phase III stability studies and establishing a stability budget, so that the data can be used to support shipping at a temperature range broader than the label storage condition, can be beneficial. For biological products, consideration of shock and vibration effects during shipping should be considered along with stressed stability conditions. This approach allows for a broader and more economical choice of shipping solutions and reduces the chance for temperature excursions, while still ensuring the safety and efficacy of the product through shelf life. When the stability data are included in the regulatory filing, many agencies are supportive of this approach.
Chasteen (Cold Chain Technologies): A recent Georgia Institute of Technology study highlighted that 90% of failures in the cold chain are attributed to human error. These errors can occur while the product is in transit, but data show the vast majority of errors are occurring during pack-out at the site of shipment origination. It is not uncommon for companies, whether in the commercial or clinical-trial space, to have multiple styles of insulated container for their various shipping needs. These containers can use several different refrigerant types and sizes. In many cases, these refrigerants require multiple stage conditioning or ‘sweating’ prior to use. These sweat and conditioning times can vary based on which refrigerant and system is being used for that particular shipment. Each package can also be packedout in very different ways, requiring employees to learn a myriad of different designs and methodologies. This confusion and complexity directly correlates to human error and costly excursions during shipment. The creation of high-performance modular shipping solutions is greatly reducing these failures. The newest shipping system families employ modular components, simple single-step refrigerant pre-conditioning, system-to-system design synergy, and only two refrigerant sizes across the entire line of payloads and durations. The emergence of simple-to-use high performance shipping systems is reducing the most prevalent cause of error in the industry today.
BioPharm: What are some recent advances in cold-chain technologies?
Chasteen (Cold Chain Technologies): Two of the advancements in technologies to better control temperature within the supply chain are analytical thermal modeling tools and advanced phase-change materials (PCMs). The combination has resulted in the industry’s most innovative thermal shipping systems. Historically, empirical testing was the only successful tool for system development. With thermal modeling, we now have the ability to truly understand the internal thermal dynamics at play. System tweaks can be made in minutes and iterative models can be run in hours. Extremely efficient designs are the result. This efficiency is particularly important when working with advanced PCMs. Advanced PCM, at the component level, is more expensive than traditional water-based refrigerant. It is crucial that PCM be used in a very precise and judicious manner. Thermal modeling is the tool to develop PCM-based systems that are less costly than the water-based variants they replace.
There is a huge shift taking place in the market. PCMs used to be solely considered for use in expensive solutions that combined the refrigerants with exotic insulation materials such as vacuum insulated panels (VIPs). The latest systems on the market combine advanced PCMs with less costly insulation materials such as polyurethane (PUR) and expanded polystyrene (EPS). These solutions are capable of being reused yet are more cost effective for single use than traditional EPS and PUR systems available. Because of the advanced designs and latest PCMs, they are better than previous water-based designs in every measurable category. Advanced PCM allows for smaller and lighter systems. This reduction in size and mass means a significant savings in both incoming and outgoing freight. Warehousing costs and carbon footprint are reduced. Most intriguing is that these new PCM systems are actually less expensive to purchase than traditional systems all while better handling the variability in real-world shipping environments.
BioPharm: Can you specify recent industry guidance with respect to supply-chain management?
Chasteen (Cold Chain Technologies): There are several new guidance documents that have recently been released or are in review for publication. One of the major changes foreseen in the US revolves around distribution in the ‘last mile.’ The last mile is the final leg of distribution to a provider, pharmacy, or directly to a patient. This portion of the industry has to operate under the tightest financial restrictions. There are four factors that are changing the landscape in the last mile: manufacturer’s transitioning from indirect to direct business models, increased pressure in the last mile from bodies such as state boards of pharmacy and accreditors, an increase in manufacturer emphasis in downstream brand protection even when title passes, and end-user awareness of temperature importance and demand for temperature indication. The Parenteral Drug Association recently published Technical Report No. 46 Last Mile: Guidance for Good Distribution Practices for Pharmaceutical Products to the End User. The adoption of this guidance poses challenges and opportunities for companies in the last mile to differentiate their service to an increasingly informed patient and provider population desiring temperature assurance.