While the global supply chain has undergone huge changes and struggles recently due to a range of factors including the COVID-19 pandemic, major weather storms and changing government policies and regulations, it has not stopped the pharmaceutical industry from launching new products.

In fact, the FDA is approving more drugs and therapies than ever before,¹ making the success of a drug launch even more important—and one of the fastest-growing categories of new products is temperature-controlled products, including many vaccines, biologics and cell and gene therapies. In 2019 alone, 45% of new drugs approved by the FDA required refrigeration or freezing,² and some analysts estimate that cold chain production will increase as much as 48% between 2018 and 2024.³

However, while the pharmaceutical supply chain is already complicated, there is added complexity around the launch of a temperature-controlled product that must be addressed. Many of these products, particularly cell and gene therapies, require precise logistics support. The variation of needs for the storage and shipment of these highly expensive products can sometimes lead to wasted or ruined product and necessitates a certain level of expertise of the industry to ensure no part of the supply chain, from manufacturer to patient, has the potential to break down.

Understanding how to effectively launch a cold chain product, while also minimizing risk and roadblocks, is becoming an increasingly vital part of healthcare logistics. When developing a launch strategy for a cold chain product, it’s important to examine the varying factors during each phase (and touchpoint) in the journey.

Before Launch
The success of a cold chain drug launch is not the result of work during one particular day or week, but the culmination of months of planning either before or after the regulatory approval of a product. Once the product is manufactured and ready for launch, you must be ready with both packaging and a trained warehouse and logistics team.

Warehouse Vendors & Training
With the number of cold chain products on the market rapidly growing, where your product is stored, preserved, and located is crucial. First and foremost, you’ll want to ensure any warehouse has cold storage equipment availability and the capability to store products at the appropriate temperatures.

During the vetting phase, ensure warehouse staff (particularly in the current times of high turnover), have been appropriately trained on handling cold storage products of varying temperatures. Businesses should provide you with demonstrated success of previous launches, including a workflow and quality assurance practices set in place to avoid unnecessary errors or spoilage of product. As part of the review of a warehouse’s training standards, one of the most important factors to review is the team’s knowledge in appropriate conditioning of coolers and pack-out techniques.

Once a warehouse vendor is decided upon, the planning for the launch can begin. Both shipping studies and validation pack-outs can ensure any and all kinks are worked out before customers expect product. An experienced third-party logistics or warehouse vendor will implement stability testing for products, develop detailed schematics for pack-outs, and properly train staff on the appropriate conditioning of ice and gel packs. Due to the unique nature of each product, the type of packaging selected by the manufacturer and the length of time it takes to pack a product are considered. A good warehouse vendor will also understand and advise on the importance of geographic locations and the estimated times products will be in transit based on their destination and what type of coolers are needed to avoid losing product efficacy.

Cold Chain Packaging Configurations
We have all received a product in the mail that wasn’t effectively packaged resulting in damaged product, and this is true even for the pharma industry. In fact, research suggests that the biopharma industry alone loses around $35 billion annually due to failures in temperature control logistics.⁴ To combat this, the pharmaceutical industry spends around $5 billion on cold chain annually. While the term “packaging” is broad, the potential financial risk of choosing the wrong type of shipper could single-handedly wreck a new launch. Typically, there are two main types of cold chain storage shippers for pharmaceutical products, each with their own pros and cons:

Passive packaging are single-use shippers that can stay cold anywhere between 48 hours to 120 hours, dependent of the packaging type. Passive packaging types use dry ice, liquid nitrogen, or water coolants packed in cardboard boxes to keep products at the correct temperature. Because these shipments can weigh less than other options, they are the least expensive option. However, these types of packaging are also the most prone to product damages or temperature variations due to delays in shipments, or handling errors resulting in incorrect storage temperatures beyond the packaging validation. Even still, this type of packaging is the most commonly used in the industry.

Active shippers are similar to refrigerators, keeping products at a set temperature the entire journey, assuming there is the availability of electricity to plug in. Because these containers are typically heavier than passive shippers (needing refrigerants and other equipment), this type of shipper is more expensive to ship due to the weight. Additionally, it requires specific transportation and handling that will enable the container to stay plugged in in order to keep the correct temperature.

It’s worth noting that one reason active shippers are becoming more popular is that they are more sustainable, because they can be re-used. Estimates⁵ suggest the world’s cold chain represents 3 to 3.5 percent of greenhouse gas emissions, and there is a growing movement to develop more sustainable and recyclable shipping containers.

As part of the packaging decision, another major decision to keep in mind is how the shipper will handle a product’s temperature requirements. While 80% of all pharma cargo6 is transported between 15°C – 25°C.; cold chain products are increasingly needing different, and more specific temperatures. The three most common are controlled room temperature (20°C to 25°C), refrigerated (2°C to 8°C), and frozen (below 0°C) to cryogenic which can be as cold as −150°C). However, even then, cryogenic products have varying temperature requirements (and often specialized packaging requirements). It’s necessary to choose a shipper that will ensure products stay at the correct temperature throughout the journey from point A to point B, and simultaneously can protect the products from the normal turbulence associated with shipping and handling.

During Launch
The day of a launch can be one of the smoothest—or rockiest—parts of the launch, often because it is the most visible moment and time-sensitive. The most important factors during this phase are transportation options and monitoring ability.

Choosing Methods of Transportation: Carriers and Couriers
Whether you use a carrier or a courier is largely dependent on how soon a product needs to arrive at its destination. CAR-T and precision medicines have shorter windows of times compared to more traditional biologics that can remain stable longer.

Oftentimes, the decision about how your product will be transported depends on the location of the product in relation to the location of the final destination. It’s important to think through the questions that can affect the launch: Does it need to be transported by freight, air or sea? How soon does the product need to be there? What are the best days to ship product? Is this a small batch (e.g., precision medicine or rare disease product) or a larger-batched product (e.g. COVID-19 vaccine)?  What limitations does your customer have at their receiving dock?

No matter which transportation method is selected, this is a key point on the supply chain where the product temperature could be at risk as the carriers or couriers will be handling the completed pack-outs and ensuring outside temperatures, humidity, etc. are taken into account when necessary. One of the most important factors is to ensure you, or your logistics vendor, have open communication with these transportation services to answer any concerns.

Monitoring & Supply Chain Visibility
The monitoring of cold chain products is largely considered one of the most serious cold chain challenges affecting the pharmaceutical industry. According to the World Health Organization (WHO), more than half of vaccines are wasted worldwide,6 which is just a small portion of the pharma cold chain product available. Now, with the arrival of precision therapies and the rise in cold chain products, the continuous monitoring of these products during transit is vital not just for costs, but also to ensure patient safety.

Prior to the advent of the internet of things (IoTs), most cold chain monitoring was done manually via thermometers.  This approach could often be prone to errors including: human error of temperature checks, wrong placement of thermometer, temperature fluctuations during transit vs. continuous monitoring. Now, with 32% of pharmaceutical executives stating that temperature monitoring is their most urgent concern,⁶ the cold chain monitoring industry continues to grow⁷ to match these expectations.

Pharma manufacturers must decide if their product needs continuous automatic data tracking for temperature-controlled products, or if they are comfortable with temperature “tells” monitored by checking coolers or packaging at major touchpoints. Often, if temperature excursions occur, logistics vendors will use chain of custody to determine where the breakdown in the cold chain happened for reimbursement issues.

Another important aspect of monitoring during the launch is understanding the current supply chain. Sending a product to an area experiencing a big winter storm (like Winter Storm Uri in 2020) would most likely result in delivery delays, and likely, product deterioration, due to a supply chain disruption. These types of issues can easily be avoided with a reliable monitoring system in place. While the product may be delayed in the initial launch intentionally in this case, it will reduce the risk of ruined product, financial losses and unhappy customers.

Overall, it is visibility of your products and inventory into the supply chain that is becoming more necessary as a whole. Think through what types of monitoring and supply chain both you and your customer will need to not only ensure the safe delivery and handoff of a product, but a good relationship as well.

Arrival at Site of Care
While the chain of custody for most pharma manufacturers ends at the delivery, there are still ways to safeguard a launch is successful after the arrival.

The most important step is understanding and communicating when and where temperature-controlled products should be delivered to ensure appropriate handling and staff ready to manage them. This will ensure final temperature checks at delivery act as the final chain of custody handoff, and the customer is prepared for how to handle the product after delivery.

For more complicated medications, pharmaceutical manufacturers may consider providing documentation to customers for the handling of cold chain products to ensure there are no issues (often a standard of care that offers step by step instructions to help employees who may be unfamiliar with a new drug understand the temperature-controlled requirements (e.g. process for warming it up; how long it lasts in a refrigerator, how long a refrigerator can remain open, etc.).

We could also mention that, depending on the requirements of the product and how frequently it is used, manufacturers might consider working with large sites of care (hospitals) to install RFID cabinets, which enable the customers to store cold-chain products on site and use them when needed.

When a small temperature fluctuation can cause problems with cold-chain medications or make it unsafe for patients to use, the room for error increases dramatically. Understanding the most common issues that arise from cold chain launches is the first step to creating a smooth process saving time, money and patient lives. 

References

1. https://qz.com/1785058/the-us-fda-approved-more-drugs-than-ever-in-the-last-decade/
2. https://finance.yahoo.com/news/direct-relief-triples-pharmaceutical-cold-201200677.html
3. https://www.directrelief.org/2021/10/direct-relief-triples-its-pharmaceutical-cold-chain-capacity-as-global-demand-surges/#:~:text=Cold%20chain%20is%20an%20increasingly%20important%20part%20of,approved%20by%20the%20FDA%20required%20refrigeration%20or%20freezing.
4. https://www.aircargonews.net/sectors/pharma-logistics/failures-in-temperature-controlled-logistics-cost-biopharma-industry-billions/#:~:text=26%20%2F%2007%20%2F%202019%20The%20biopharma%20industry,according%20to%20IQVIA%20Institute%20for%20Human%20Data%20Science.
5. https://www.sciencedirect.com/science/article/abs/pii/S0959652619329233
6. https://www.accenture.com/_acnmedia/PDF-166/Accenture-Pharmaceutical-Supply-Chain.pdf
7. https://www.prnewswire.com/news-releases/cold-chain-monitoring-market-worth-10-2-billion-by-2026–exclusive-report-by-marketsandmarkets-301436015.html

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As Director of Client Relations and Business Implementations for Cardinal Health 3PL (Third Party Logistics Services), Shantese Marchbanks guides biopharma companies in setting up new programs tailored to unique market needs and product profiles. With a background in quality, compliance and finance, she has helped establish new business SOPs with more than 100 sites of care to support cell and gene therapies.

As Vice President of Operations, Joel Wayment leads Cardinal Health Specialty Solution’s 3PL business. Under his leadership, Cardinal Health 3PL (Third Party Logistics Services) has grown become an industry leader in third-party logistics, providing warehousing, distribution, and order-to-cash services with products across a wide range of therapeutic categories including unrivaled experience bringing cell and gene therapies to market.