High-fidelity data and real-time monitoring key in preventing temperature excursions across the pharmaceutical cold chain
Global specialty drug distribution industry market growth
Growing at a compound annual growth rate (CAGR) of 14.2 percent since 2022, the global specialty drug distribution market is expected to reach a value of nearly US$6 billion by 20301.
This is partly driven by the rise in the development and manufacturing of new vaccines and of cell and gene therapies (CGTs). CGTs are promising innovative therapeutics for treating chronic diseases but often require cryogenic storage for stability. Patient-specific CGTs also add extra intricacies due to the need for temperature-controlled transport to collect patient cells, manufacture the CGT, and then administer it to the patient. This results in tight shipping windows, cold storage infrastructure, thermally-controlled packaging technology, and strict regulatory requirements to satisfy manufacturer and patient needs.
To help overcome these challenges, companies turn to third party logistic suppliers (3PLs). Following robust SOPs, 3PLs provide solutions for pharmaceutical cold-chain logistics to ensure efficient temperature-controlled delivery of a drug substance or product.
Devising a strategy early
It is important to plan and implement a cold chain supply strategy early in product development — ideally between phases IIb and III — to avoid errors or delays. Though a product may not make it to market, this proactive approach identifies and mitigates problems so that the therapy reaches its destination swiftly once approved. It also aids in eliminating the risk of an excursion event when a time- and temperature-sensitive pharmaceutical product (TTSPP) is outside of a set range or time.
However, even when accounting for all possible risks, unforeseen circumstances can still lead to temperature excursions during shipment. But how do we know if this occurs, and what would be done to ensure it does not happen again?
The required storage and handling conditions (e.g., temperature range and humidity) are determined based on product stability data. As an excursion event can impact drug efficacy and safety, preserving these product conditions throughout shipping and delivery is vital.
When utilizing temperature monitors in the past the only way to know if a temperature excursion had occurred at any point throughout the journey was after delivery when the temperature monitor was read out. Depending on whether the temperature monitor was provided by the logistics company or the shipper, it could take between hours to days to evaluate if a temperature excursion occurred. During that time, the product would have to remain in holding, wasting valuable time. Including sensors with shipments can allow real-time monitoring of the delivery conditions, including location, light exposure, humidity, shock, and temperature. With accurate tracking, any excursion event, no matter how small, will be recorded and reported to shipper and the logistics partner. This data then undergoes careful evaluation to ensure a product is safe for use.
Real-time monitoring also enables quick response. For example, tracking the shipment route ensures product location and delivery schedules are on track. If a deviation is reported, implementing a continuity plan or devising a new strategy via direct contact with the shipment will aim to maintain the tight timeline. Data collection throughout the delivery timeline by the logistics partner assures the pharma company of the validity of their product before patient administration. This data is invaluable for decision-making throughout the client's timeline.
The tracking data collected has great value in helping to make informed decisions at every stage of a pharma company’s critical time and temperature-sensitive supply chain.
Corrective measures can be taken to re-establish conditions if an excursion event is recorded. However, there is a patient at the end of the supply chain and lives can be at stake, so any recorded discrepancies must be investigated before any drug is given to a patient, even if product conditions are quickly re-established.
If subject to a temperature excursion event, a decision tree informed by stability testing information, collected data from tracking, and the optimized distribution strategy can be used to determine whether to release a drug batch. The drug will either be deemed safe to be administered or rendered useless. A decision tree considers each possibility as follows:
Decision tree example:
Analysis and continuous improvement
In addition to real-time monitoring, all collected data can be analyzed to highlight any recurring problems or areas for improvement. For example, if one route often leads to more delays due to traffic, then an alternative route can be chosen. Or if a particular packaging choice leads to statistically more excursion events, then alternative packaging can be sourced. This constant improvement can help to build a more robust strategy and further mitigate risks associated with cold-chain supply.
Excursions can occur anywhere within the production and distribution timeline. As manufacturers must adhere to good manufacturing practice (GMP) and good distribution practice (GDP) guidelines, recording any temperature variations throughout this timeline is critical.
Having a logistics partner with robust temperature-controlled handling and transportation capabilities and a clear product-tailored strategy is essential for efficient and safe distribution and ultimately to ensure business continuity. Coupled with accurate technology to monitor excursions, a safe and efficacious product can be delivered to its destination, ready for patient administration and helping to create healthier futures.