Cure for the Common Cold Chain Break

Donald T. Allegra, MD, is a nationally recognized infectious diseases physician, and a founder of the largest clinical practice in the state of New Jersey focusing on prevention, diagnosis, and treatment of infectious disease. He estimates that temperature-sensitive medicines used in his practice, primarily vaccines and antibiotics, represent more than 80 percent of his drug inventory.

The physicians and staff there are well trained in the rigors of storing and handling cold chain medicines. But mistakes happen. Delivered, unopened boxes may sit overnight on the front step of the office. An electrical storm can shut down power. Any one of a number of circumstances may impact the carefully controlled temperature environment and lead to cold chain breaks.

An increasing number of pharmaceutical products prescribed in the US—including insulin, vaccines, biologics, chemotherapeutic agents, blood products, and many antibiotics—are temperature-sensitive and require special shipping and storage processes to ensure they stay within the specified temperature range for the entire life of the product.

The logistics and service market to manage distribution of cold chain pharmaceutical and biotech products also is growing. The dollar value of cold chain biologics and pharmaceutical shipments was $147 billion in 2008, and is projected to rise to $187 billion in 2011, according to the Biopharma Cold Chain Sourcebook 2010.

But while the US pharmaceutical industry keeps up with the commercial demand for temperature-sensitive medicines, it falls behind in applying technologies that manage the cold chain from point of manufacture to point of administration to patients.

The cold chain distribution process officially begins when products are released from the manufacturer's warehouse. From that point on, the cold chain journey often is a complex series of multiple touch points, facilities, vehicles, modes of transportation, and personnel.

Of late, the industry is particularly concerned about the final leg of the cold chain—the "last mile"—which refers to the critical period of time between delivery to an office/clinic/pharmacy and patient administration. It is during this time when temperature-sensitive, life-saving medicines are most vulnerable to cold chain breaks.

Concern About Risk to Patients

The reality is that cold chain breaks can, and do, happen at any time. They are surprisingly common. Research tells us that most physicians who handle temperature-sensitive medicines have experienced a cold chain break at some point, and they are very concerned about the associated risk to patients.

According to a recent Harris Interactive research study of primary care physicians (PCPs) and specialists about their experiences and perceptions about the pharmaceutical cold chain, 83 percent of PCPs and 72 percent of specialists reported experiencing delivery/storage-related breaks in the cold chain.

The study also shows that physicians overwhelmingly agree that cold chain breaks—and the cumulative exposure of drugs to temperatures outside the specified range—pose risks to patients and public health.

They are specifically concerned about loss of product potency, a known effect of temperature abuse. And across the study primary care and specialist physicians (pediatricians, endocrinologists, hematologists/oncologists, and rheumatologists) reported being concerned about potential adverse events related to heat-damaged products, ineffective treatment interrupting protocols, and ineffective treatment and/or no symptom relief.

Not surprisingly, the PCP and pediatricians subgroup reported being particularly concerned about the potential for outbreaks of preventable disease caused by the administration of heat-damaged vaccines. Pediatricians are the highest prescribers of vaccines. Herein lies the problem: Perhaps unaware of temperature damage, they could unwittingly administer the medicine, putting patients at risk for treatment failures, interruption in treatment protocol, and possible adverse events.

Or, suspecting temperature damage but without a means to confirm it, they discard medicines that are OK to use. In both cases, the impact of this issue has broad-reaching effects.

Impact of Product Waste

All temperature-sensitive pharmaceutical and biologic products—those that require refrigeration to avoid heat damage, and those that must avoid freezing—are at risk of temperature damage if handled improperly.

In an effort to understand the public costs of improper vaccine storage, the CDC's AIM Vaccine Storage and Handling Working Group examined and quantified the financial value of incidents that cause heat and freeze damage resulting in vaccine waste. The study looked at vaccine waste resulting from storage failures, from 45 of 64 participating immunization programs, during an eight-week period in 2009.

The study included both heat and freeze incidents during storage. Heat damage is known to cause a reduction in vaccine potency, and has the potential to render a vaccine completely ineffective. Freeze damage destroys vaccine; and freeze events are particularly difficult to identify in products previously frozen, and then thawed.

The study found that the total value of publicly funded vaccines wasted in the eight-week time frame was $1,167,781. Extrapolated to one year, the value for publicly funded vaccines is $7,590,580. Recall these figures reflect waste costs for storage-related events only, and do not include events causing damage and waste that occur during shipping prior to arrival at physicians' offices.

Looking at it another way, consider that the US government through the Vaccines for Children Program (managed by the CDC) purchases approximately 80 million doses of vaccine per year, at an estimated average price per dose of $35. Assuming a 3 percent rate of waste due to adverse temperature exposure on $2.8 billion per year spent on vaccines for children (a 2002 study estimated 1 percent to 5 percent), the cost of vaccine waste is potentially $84 million annually.

The Healthcare Worker Conundrum

Some temperature monitoring devices are shipped in the product packaging to monitor temperature during various segments—but not during the entire journey. Others report temperature excursions at various points during transportation, but lack the capacity to track combined heat exposures over time that might cause heat damage.

In more than 80 countries, cumulative heat-monitoring devices are used on individual units; they stay with the medicine from start point to end point. Each is equipped with an indicator so healthcare workers can easily identify whether product has accumulated exposure of temperatures over time that may have caused heat damage.

This technology is available in the US but thus far is not widely used.

It is also important to note that temperature excursions occurring during the cold chain journey do not necessarily translate into temperature damage. Many products can tolerate multiple excursions. However, too many excursions outside the required temperature range, and for too long, may cause irreversible temperature damage.

On a global level, extreme climate conditions and unsophisticated refrigeration systems pose significant challenges to cold chain processes. To address this clear threat to the success of immunization programs in developing countries, UNICEF and the World Health Organization first mandated that miniaturized vaccine vial monitors be affixed to individual vaccine vials distributed through their programs in 1996.

The HEATmarker devices used in these programs provide consistent, cumulative, unit-specific temperature monitoring, and include an indicator that shows whether the product has been exposed to potentially damaging temperatures. Since 1996, more than 3 billion HEATmarkers have been affixed to every vaccine distributed globally through UNICEF. Today, 37 global vaccine manufacturers use HEATmarker vaccine vial monitors.

Here, however, a gap persists between the perceived need for such indicators in a developed country such as the US, and the reality of patient risk and product waste associated with cold chain breaks.

Physicians who regularly handle cold chain medicines are looking for a better way. More than four-out-of-five physicians (89 percent PCP/pediatricians and 87 percent specialists) agree on the importance of a device affixed to individual units that indicated whether a product has been exposed to potentially damaging heat.

It's time for the US industry to acknowledge domestic cold chain issues, take a look at technologies used successfully at a global level, and ascertain their value to the healthcare community here. Equipping healthcare workers with the information they need to manage their temperature-sensitive medicines and ensure the thermal integrity of these products helps everyone.

Ted Prusik, PhD, is Senior Vice President of Temptime Corp. He can be reached at tedp@temptimecorp.com