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Faster-than-average growth of biologics, more global trade to emerging countries, and widening regulatory requirements will propel the activity
A specialized area of life sciences distribution is undergoing a boom right now: temperature-controlled shipping of pharmaceuticals, vaccines, blood products and clinical trial materials (CTMs). It is well known that national and international regulatory authorities are looking more closely at how temperature-controlled pharma shipments are being managed. And it is equally well known that there is a growing pipeline of commercial and near-commercial biotech products that will often require close control of temperature. One of the latest to be approved—Dendreon’s highly anticipated prostate cancer “vaccine”—stands out for requiring temperature control both as a patient’s blood is conveyed to Dendreon’s processing centers, and as the treated product is returned for infusion.
Looking at cold-chain biologics and pharmaceuticals alone, the dollar value of shipments was $147 billion in 2008, and projected to rise to $187 billion in 2011—a 27% growth rate, more than double that of overall biopharma growth (Fig. 1). These data come from a first-of-its-kind report, “Biopharma Cold Chain Sourcebook 2010,” published by Pharmaceutical Commerce. Blood plasma and sera has been projected (by Evaluate Pharma) as an $18-billion global industry, rising by 8% per year to 2014, or roughly $23 billion. Vaccines are projected to grow by an identical rate, from $20.6 billion in 2008 to about $26 billion in 2011. The CTM industry has been estimated at $50 billion worldwide, the majority of which is biotech-based. Even if this stays flat through 2011, the total value of cold chain product shipments for life sciences will be nearly $246 billion in 2011.
Evidence of this growth can be seen in the number of air carriers, third-party logistics firms (3PLs) and packaging and storage firms bulking up their cold-chain services. UPS, FedEx, DB Schenker, DHL and most other life-sciences 3PLs now have specified cold-chain services (Pharmaceutical Commerce, Jan/Feb, p. 21); air carriers with specified cold-chain services include American Air Cargo, Continental, Delta, Cathay Pacific, Air Canada and Emirates SkyCargo; cold-chain unit-load devices (ULDs) such as Envirotainer and CSafe, and a growing number of packaging and instrumentation companies have joined the fray.
“Biopharma Cold Chain Sourcebook 2010” surveys growth rates for pharma, biotech, vaccines, blood products and clinical materials, US and international regulatory bodies such as FDA, USP, PDA, IATA, MHRA and others, and air, ground and ocean carrier modes. It includes packaging materials and technologies, refrigeration systems and instrumentation.
Traditionally, cold chain procedures have come out of stability testing as pharma companies move their products toward commercialization. Most products are expected to be kept in a temperature regime of 2-8°C (36-46°F); some at 2-25°C (36-77°F), and many at “room temperature” (under 25°C). Industry labeling and safety guidance has allowed for a limited amount of excursions above these ranges, but historically the duration of those ranges has been poorly reported. For many refrigerated products, the need to keep it from freezing (0°C) is as important as keeping it below 8°C.
Temperature-controlled shipping will grow purely on the basis of increased shipments, but the entire activity is going to get more complicated—and more expensive—as a result of evolving regulations both in the US and worldwide. In 2009, the World Health Organisation began updating its Good Distribution Practices documents; the Parenteral Drug Assn. began a revision of its “Technical Paper #39,” and the International Air Transport Assn. issued new guidance on perishable air cargo. At the same time, the Healthcare Distribution Management Assn. issued a report, “Managing Cold Chain & Temperature Sensitive Products.” In early 2010—outside the scope of the Sourcebook, the US Pharmacopeia issued a top-to-bottom proposed revision of USP <1079>.
Comparable updates and revisions are occurring at Health Canada, the UK’s Medicines and Healthcare Products Regulatory Agency, and European Union good manufacturing practices.
The direction of these revisions and updates is exemplified by the summary of the proposed USP <1079>:
“Good storage and transportation practices require that organizations involved in the storage and/or transportation of drug products maintain a quality management system (QMS) that includes a storage management system (SMS) and transportation management system (TMS). Together, the QMS and its component SMS and TMS help ensure that proper storage and transportation practices are in place from the point of manufacture to the point of end use or administration.”
All these “systems” will require additional manpower, data collection and reporting, both from manufacturers and from their shipping and logistics service providers.
Logistics service market
The Sourcebook estimates total biopharma logistics costs of $43 billion in 2008, of which $5.2 billion, or 12.1%, is devoted to temperature-controlled shipping (Fig. 2). This temperature-controlled segment splits between $3.2 billion for logistics and transport, and $2.0 billion for packaging materials and instrumentation.
Cold-chain shipping started out simply with ice-cooler-type containers packed with dry ice, ice or gel packs. Now there are purpose-built superinsulated containers (at roughly $100 per container) that include gel packs with specific temperature ranges that can be “dialed in” by selecting the appropriate freeze-melt points. Package design and component technology has advanced to where a shipment can be kept at temperature (usually, 2-8°C) for two or even three days, in some cases making overnight delivery unnecessary.
A comparable evolution is occurring with instrumentation, which is migrating from simple color-coded indicators attached to a container to radio-enabled sensors that can be read remotely. Whereas temperature profile data in the past had simply been a record of high and low temperatures experienced during a shipment, to timestamped measurments along an entire shipment route, with accumulated data being downloaded for recordkeeping procedures to be satisfied.
Nearly all insulated containers with refrigerants are defined as “passive” temperature protection; “active” protection, particularly for air cargo, involves battery-powered or plug-in ULDs, heating as well as cooling machinery, and the ability to report data not just at the end of a shipment transit, but even at intermediate points along the way. The active ULDs are equipment that is inherently reusable; reuse or recyclability is now coming to the fore with the passive cartons and gel packs. Some packaging makers have set up automatic-return processes so that the package can be reconditioned and reused; others have made arrangements for recycling through, for example, collecting expanded polystyrene foam and sending it to recycling firms for that material; others have gone the “green” route of using renewable materials. All of these efforts can be claimed by pharrma manufacturers as a way to shrink their carbon footprint.
In line with industry projections of faster growth rates in emerging markets, cold chain activity is rising faster in those markets as well. While North America and Europe will grow by about 19%, Asia is heading for 50% growth, and the rest of the world by 33% (Fig. 3). While much of this represents the same biological products coming into US and European markets, a significant part of the Asia and ROW market will come from vaccination programs which have expanded significantly through philanthropic efforts like the Bill and Melinda Gates Foundation, which announced a $10-billion grant for vaccine development and application over the next decade. While vaccine development and use will expand in coming years, the growth in cold-chain activity will not necessarily be linear with the number of dosages produced; there are efforts to package vaccines more efficiently to expedite their transportation, and to develop room-temperature versions of some (which could still require temperature control, if not refrigeration).
That room-temperature vaccine development raises another factor that could have tremendous influence on the overall temperature-control services market. Some of the latest regulations require temperature management of “controlled room-temperature” (CRT) products—into which a vastly larger cross-section of the pharma industry fits. As study of cold-chain shipping practices has advanced, the realization that CRT products can be subjected to extremely high temperatures (in the trunk of a car or truck, for example) as well as extremely low (in an air shipment traveling without heated storage compartments). While CRT products will not require the elaborate safeguards applied to refrigerated products, they will require some level of insulation, and some level of temperature monitoring, according to the Sourcebook.
“Biopharma Cold Chain Sourcebook 2010” is available from Pharmaceutical Commerce at firstname.lastname@example.org, or by