The rapid growth in the biopharmaceutical and vaccine industries is driven in part by increased demand in emerging markets, particularly throughout Asia. China is rapidly becoming a major player in biopharmaceuticals – a recent report by IMS Health predicted that China is poised to become the world’s third largest pharma market.

The same report suggested that a key limiting growth factor is China’s lack of cold chain infrastructure. According to industry experts, some organizations have even restricted their delivery radius to around 300 km to avoid the risk of temperature fluctuations during longer transports.Maintaining a secure cold chain through the storage, handling, and transportation of temperature-sensitive biological products assures they reach their intended destination without becoming compromised. While agricultural products will remain the leading product category, pharmaceuticals are an increasingly important market segment in China, with vaccines and blood products acting as the primary drivers of growth in the short term.

The market for vaccines is supported in large part by the Chinese government, which in 2007 expanded the National Immunization Plan (NIP) which seeks to eliminate measles and control Hepatitis B and decrease rates of other target diseases.

The Cost of Cold Chain Dependence

Cold chain dependence presents many obstacles in emerging global markets, and perhaps the most significant is cost. In its fifth annual forecast, Pharmaceutical Commerce reported 2014 pharma logistics spending was estimated at $8.4B worldwide. Of that, $5.6B was in transportation costs and $2.8B was in specialized packaging and instrumentation, including insulated boxes, active temperature-control shipping containers, and various sensors and recorders. The forecast revealed the top driver for cold chain logistics is increased demand for cold chain products in developing markets.

According to the World Health Organization (WHO), reliance on a cold chain increases vaccine costs by up to 20% and poses a significant barrier to patient access, particularly in Asia, where refrigeration systems and temperature-controlled storage are in short supply.

Contrast that with the fact that Asia is expected to account for the largest share of predicted cold chain growth – more than $1B through 2018 – and it’s easy to see why cold chain alternatives are needed. The fact is, it costs more to keep products at 2–8°C or frozen than it does to keep them at uncontrolled ambient conditions. It also costs more to pack and transport products cold, and additional costs are incurred when monitoring products during transport and testing for efficacy and spoilage.

Researchers Examine Alternatives to Traditional Cold Chain

The effort to control communicable diseases has increased demand for a comprehensive vaccination program in China, and out-of-the-box delivery methods may be required if large-scale vaccination efforts – particularly in remote rural regions – are to be successful. As the second largest country in the world, China is also the most populous, with over 1.3B citizens. Companies hoping to deliver temperature-sensitive biologics in China face a landscape characterized by varied terrain and weather extremes that could delay or impede transport times.

A November 2007 study examined outside-of-cold-chain delivery strategy in remote regions of western China where populations live far from the county health center and lack a cold chain infrastructure. The study’s objective was to assess the effects of exposure to temperatures outside-of-cold-chain on vaccine potency.

One of the strategies involved delivering vaccines during the colder winter months. China’s western plateau sits at 3,000 to 5,000 meters above sea level and average temperatures range from −22°C to −3°C between November and January. The ambient temperature is sub-zero from the beginning of October to the end of April.

The winter delivery strategy stemmed from a common misconception that the term “cold chain” refers only to the avoidance of heat during shipping. In fact, extreme cold temperatures can be equally harmful to vaccine efficacy. With that in mind, the study investigated whether hepatitis B (HepB) and measles vaccines stored and transported in the winter were subjected to below freezing and/or high temperatures during routine distribution.

For the study, researchers selected random sight clinics with ambient temperatures ranging from −7.9°C to 12°C during the study period. To examine changes in efficacy due to exposure to temperatures colder or warmer than established guidelines, the HepB vaccine was chosen as representative of a cold-sensitive vaccine, while the measles vaccine was selected as a representative of a heat-sensitive vaccine. Both vaccines are routinely used in China.

The study concluded that due to unpredictable temperature fluctuations during transport, an outside-of-cold-chain vaccine delivery strategy did not effectively replace the vaccine cold chain. A faulty refrigeration system, products exposed to sunlight while being transported in a truck bed, and excessive exposure to air conditioning were all cited as risk factors for vaccine spoilage. As a result, several regions in the area began to establish their own cold chain systems, with particular emphasis placed on cold chain training and education.

Moving Beyond the Cold Chain

WHO estimates that more than 1M children under age five die each year from vaccine-preventable diseases – the majority of them in developing countries like rural China. Improved technology, innovative delivery transport systems, and expanded education for vaccine administrators in emerging markets can all contribute to increasing vaccination rates and ultimately saving lives. But, some researchers are also looking at a “beyond the cold chain” solution that could change the way vaccines are stored, transported, and delivered.

VBI is developing novel technologies that seek to expand vaccine protection in large underserved markets like China. VBI’s Liquid Particle Vaccines (“LPV™”) technology enables the development of vaccines and biologics that can withstand storage or shipment at constantly fluctuating or elevated temperatures. Thermostable vaccine delivery could decrease reliance on the current cold chain infrastructure in growth markets like China.

VBI has completed proof of concept studies on a number of vaccine and biologic targets including Influenza, rabies, MMR, and Herceptin. LPV™ technology allows for rapid reformulation of both existing vaccines and vaccines in development.