Innovaciones y adaptaciones de la cadena de frío
El ascenso de los ensayos clínicos
The rise of targeted therapies and the globalization of specialty pharmaceutical commercialization present a host of opportunities for manufacturers. The foundational premise is clear: More commercial and clinical trial drugs are being shipped to more patients in more countries than ever before. Healthcare is becoming more innovative and more accessible at the same time.
With these opportunities, however, come great challenges. The increase of global clinical trials for high-value cold chain products means that the stakes—and the costs—for each trial have risen dramatically. The distribution of specialty medications to emerging markets means that the total supply chain must be evaluated more stringently. The industry now operates in an environment where there is no “acceptable loss” of product or samples. As a result, global manufacturers must constantly evaluate the advances in technology, processes, and resources that keep cold chain products safe. They must remain vigilant over the growing and diverse risks in the supply chain and understand the need for increased expertise from their partners. They must stay focused on continuous improvement across all parts of their supply chain to ensure that drugs are delivered safely and effectively, while risks are mitigated appropriately.
Here, we explore three macro-trends in the global pharmaceutical supply chain—specifically the temperature-controlled supply chain—and key takeaways that manufacturers should consider as they work to drive new growth globally.
Targeted therapies and unique temperature needs
Pharmaceutical manufacturers have seen a significant shift in their development goals and processes. The pursuit of the next blockbuster, small-molecule product has given way to excitement around new, targeted therapies, biologics, and personalized medicines—all of which are driving demand for better temperature control in the supply chain.
Increasingly, there is a need for more than just cold shipping. Instead, there is an expanded need for a highly connected and functional supply chain. In fact, “cold chain” no longer accurately describes the full suite of solutions that manufacturers need. The industry is moving toward “temperature control” as the all-encompassing term, in recognition of the wider range of new temperature requirements for biologic products. From samples and biologics shipped at “body temperature” (close to 37 °C) to controlled room temperature (about 20–25 °C), all the way down to ultra-frozen products stored at -80 °C, the new spectrum of temperature needs makes it clear that the traditional cold chain (a range of 2–8 °C) is no longer sufficient to accommodate all product needs.
New temperature requirements necessitate new packaging solutions. It’s difficult to maintain product temperatures in a laboratory or storage setting, and the difficulty increases exponentially when products must travel at a consistent temperature across thousands of miles over the course of hours or days. The right packaging is essential to ensuring product integrity.
Fortunately, the options for packaging and monitoring technologies have expanded significantly in recent years. Semi-active packaging, including expanded polystyrene (EPS) and expanded polyurethane (EPU) systems, is still common and is often is the more economical choice for local, short-distance transports. Semi-active solutions are unable to regulate their own internal temperatures and require different packaging configurations seasonally, even within the same route. For this reason, semi-active packaging is best suited for controlled, short-haul routes. Many semi-active solutions are only intended for use a single time and must be discarded afterward, causing them to be somewhat of an environmental liability.
New options are focused on offering longer durations of temperature control with lighter materials that have a smaller environmental impact. Passive packaging solutions are more technologically advanced and provide proven temperature control over long distances. These solutions rely on specific engineering to create a highly stable interior storage environment. Independent testing indicates these solutions perform five to seven times more efficiently than semi-active solutions. Phase-change material (PCM), comprised of paraffin or salt-based solutions, allow for more precise temperature control to maintain product stability over long distances or through extreme climates. Many packaging manufacturers are now developing their own vacuum-insulated panel (VIP) containers, combined with PCM solutions, for easier handling and storage.
On the monitoring side, GPS technologies and tracking equipment that include automatic start-up and shutdown mechanisms (so they can be used safely on flights) offer a real-time view into a shipment’s status and data-driven peace of mind throughout a product’s entire journey.
Although monitoring technology can be a benefit, it can also be a disadvantage for some products. Manufacturers should partner with organizations that can help them find the solutions that align with their product-specific needs. Selecting too much technology (e.g., using a container with an electric-powered refrigeration system when a PCM-based solution would work), can create unnecessary expense. Selecting not enough protection can risk the integrity of a product.
Global clinical trials and expanding market presence
In tandem with the shift in the types of drugs being created, there’s also a shift in where drugs are being developed. It is estimated that pharmaceutical sales in Brazil, Russia, India, and China will grow to nearly a quarter of a trillion dollars by 2016 (1). There are more than 186,000 registered clinical trials taking place across the globe, and global pharma’s volume has more than doubled over the last decade (2).
New patient populations are needed to test the latest in pharmaceutical advances. Increasingly, regulatory bodies mandate tests need to be conducted within the specific countries in which manufacturers seek approval to launch and market a product. As a result, the importance of efficient, global clinical trials will increase dramatically in the coming years.
As the global market for clinical trials expands, there are significant hurdles that manufacturers must clear to ensure products arrive at the right place, at the right temperature, at the right time. Manufacturers and logistics partners often must navigate geopolitical roadblocks to maintain a high-performing clinical and commercial supply chain. Apart from global concerns in hot-button countries, manufacturers must consider all local, regulatory landscapes in which they do business. They must evaluate the existing capabilities in the market and disruptions in the supply chain to determine how all of these factors may impact shipping time.
Improper customs paperwork, for example, can delay or compromise even the most optimally packed shipments. Delayed flights, weather issues, or airport personnel strikes can cause product transport issues that could delay or even derail entire clinical studies. Manufacturers can avert these issues by deploying knowledgeable, trained logistics personnel within their global markets. Placed at varying locations around the world and operating within a proven infrastructure, these experts should be able to mobilize local knowledge and expertise on a real-time basis—substantially reducing risk of temperature excursions. Global expansion may be the goal, but global support has to come along with expansion. When conducting clinical trials in emerging markets with time- and temperature-sensitive medications, manufacturers should consider working with specialty logistics experts in each specific country. Local, in-market knowledge of regulations and transport infrastructure can mean the difference between keeping the clinical supply chain moving and grinding a productive trial to a halt.
Focus on risk mitigation
The financial risks of mishandled shipments are fairly clear for commercial drugs that must remain temperature-controlled: lost sales and revenue, lost productivity, and lost opportunity to improve patient lives. The risks are no less severe on the clinical side, where transportation failures involving clinical product or patient samples could result in studies being compromised. Delays and other disruptions in trials impact the expected time to market for a product, potentially putting millions or billions of future revenue dollars at risk.
As a first step, it is crucial for manufacturers to identify the needs for all of their shipped products, especially those of high value. Meeting risk mitigation and quality objectives within the framework of an effective cost/performance strategy can be a simple matter of combining the right packaging fit with the right service fit for each individual application.
Considerations for manufacturers include:
- Size of package needed
- Package type/temperature-control mechanisms
- Environmental concerns (reusable packaging or one-time use
- Temperature needs and variables (weather, location
- Best route (fastest, cheapest, ground vs. air, best controls)
- Cost of shipping
- Value of the ingredients and product
Beyond that, though, global manufacturers are also challenged with needing to understand worldwide political issues and infrastructure limitations that may impact logistics. Take the following situations as examples:
- Cambodia’s Phnom Penh International Airport has no freezer available and only one refrigerator set to one range that is neither qualified nor controlled. In conjunction with technological restrictions, clearing customs can take many days. It may be possible for logistics partners to refresh refrigerants, but there are no guarantees.
- In Laos, the rainy season lasts from August to September. With limited airport facilities, products can be left on the runway. Manufacturers can avoid unnecessary damage by sending products before or after the rainy season.
- With the growing population and spend on healthcare in Latin America, it’s an ideal location for a growth plan, but each country within the region has different regulations and resources.
Although conducting trials and commercializing in new markets represents opportunities to expand needed therapies to new patients, it also represents millions of dollars worth of risk when working with cold-chain products. Proactive planning—combined with a knowledgeable logistics partner that can help navigate global nuances—will help protect products, ensure that temperature controls are met, and increase effective use for patients.
A solution for every therapy
Manufacturers worldwide are investing more in their supply chains. A $15-billion increase in spending for global biopharmaceutical logistics is expected between 2012 and 2018 (3). As global predictive growth explodes, shippers and trial sponsors can expect an increase in regulatory and overall logistics complexities that foster in-market resources across the globe. The spend on cold chain logistics was more than $8 billion worldwide in 2014 and is expected to exceed $10 million by 2018 (3).
The rise of targeted therapies and solutions for rare diseases has created even more challenges for manufacturers, as the demand for personalized, high-value drugs with more active pharmaceutical ingredients (APIs), shorter shelf-lives, and strict temperature requirements increases. As products become more targeted, so will the logistics solutions. This trend indicates pharmaceutical companies are (or will become) more invested in supply chain operations.
Fortunately, sophisticated logistics providers are investing in new technologies and improving their capabilities in order to ensure they can successfully handle the most innovative new products on a global basis. As the supply chain continues to expand in complexity, the relationships between manufacturers and their logistics partners must also grow.
1. C. Ross, “Building BRICs: pharma’s key emerging markets are becoming giants,” PMLive, http://www.pmlive.com/pharma_intelligence/building_brics_pharmas_key_eme..., accessed Apr. 1, 2015.
2. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/resources/trends#RegisteredStudiesOverTime, accessed Apr. 1, 2015.
3. M. Lipowicz and N. Basta, “2014 Biopharma cold chain forecast,” Pharmaceutical Commerce (2014), http://www.pharmaceuticalcommerce.com/index.php?pg=supply_chain_logistic..., accessed Oct. 30, 2014.
About the Author
Nils Markmann is VP of Global Operations for World Courier.
Vol. 28, No. 5
Pages 35–37, 49