The surge in mail-order drug deliveries, amid rising temperatures and climate volatility, presents a growing challenge to the security of the pharmaceutical supply chain. Every time vaccine is subject to excessive heat or cold, for example, its potency may be diminished, according to the Centers for Disease Control and Prevention (CDC). A single exposure to freezing temperatures can destroy a batch entirely.
As can excessive heat. Earlier this year, a doctor in Australia reported to ABC News that she'd jettisoned an entire shipment of vaccines, including for meningitis, for the third year in a row when her town lost power, and thus refrigeration. Altered medications, health professional note, can be dangerous, as well as ineffective.
With these trends in mind, a pair of New Jersey inventors have set their sights on the so-called "cold chain" - the controlled transport environment of medications traveling from manufacturer to customer - with a device that will alert healthcare providers with heightened precision if a medication has reached a temperature that may have compromised it.
Called ThermaProx, the device includes a proxy sensor clipped to individual vials and syringes that mimics the temperature profile of the dose of vaccine or insulin on its final journey, rather than simply recording the ambient temperature in which it traveled. If the medication freezes, the proxy turns blue; if it overheats, it turns a deep red.
How it Works
The proxy has the same amount of liquid as the medication in a container that is exactly the same size, while the solution has the physical and chemical properties of the product it monitors, as well as its thermal mass. It contains a solution of a reactive ingredient in water that changes color when another reactive ingredient, encased in wax microcapsules that are suspended in the solution, is released as the wax melts with overheating or cracks upon freezing.
"For example, both the vaccine material and the indicator can be water solutions or dispersions and hence have similar heat capacities such that the vaccine and the indicator would behave similarly at the same temperature," noted Robert Geissler, a co-founder of the company ThermaProx, which is named after the technology, and an NJIT alumnus with a degree in electrical engineering.
By comparison, pallet-sized shipments include electronic recorders that monitor and record, for future reference, the ambient temperature of the container in transit. The pallets are broken down by large wholesalers and the recorders may or may not accompany the cases that are later distributed to smaller wholesalers, where they are further broken down into cartons and boxes that typically have no temperature monitor at all. Patients thus have no idea of their medication's thermal history.
The Rise in Mail-Order Drugs
"Now that more and more temperature-sensitive medications are being sent to patients by mail or delivery services, the probability of temperature excursions becomes greater," said Nathaniel Cooperman, who conceived of the device several years ago and sought Geissler's help to build it.
In its 2019 Vaccine Storage and Handling Toolkit, the CDC notes that "each year, storage and handling errors result in revaccination of many patients and significant financial loss due to wasted vaccines. Failure to store and handle vaccines properly can reduce vaccine potency, resulting in inadequate immune responses in patients and poor protection against disease." Moreover, the agency adds, these experiences can cause patients to lose confidence in their treatments.
A 2017 study on freezing incidents in the cold chain conducted for UNICEF found that in wealthier countries, the percentage of shipments found below recommended temperatures was 38%, as compared with 19.3% in lower income countries. The comparable figures for freezing in storage units were 33.3% and 37.1% respectively.
"The incidence of medications subject to temperature-damage in transportation and storage is a long-recognized problem. Within CDC's Vaccines for Children program, losses are routinely reported. An Inspector General's 2012 report on the program found that 75% of the samples in the study exceeded temperature criteria for five hours or more," Cooperman noted. "According to another recent report, 22,000 patients in Ventura County, Calif. had to be revaccinated, because the vaccines - from flu, to measles, to pre-adult inoculations such as the human papillomavirus (HPV) - had been stored poorly. The list goes on.
He added: "This bodes ill for one of our newer, powerful classes of medications - biologics - which are deployed against some of the most difficult to treat diseases such as autoimmune disorders cancers, among others, and are extremely sensitive to temperature excursions, high or low."
The inventors note that the market for vaccines in the U.S., Europe and Asia alone is projected to be worth $66.45 billion by 2027, at a compound annual growth rate of 6.7%; the global biologics market was valued at $276.6 billion in 2015. The prefilled syringe market, which has a huge potential for personalized patient medications, including individualized vaccines and medications, is estimated at around 7 billion units per year and growing.
Geissler, a serial entrepreneur with four decades of experience in engineering technology sectors such as aerospace and semiconductors, and Cooperman, the developer of diverse chemical processes for the efficient utilization of materials, met several years ago as virtual tenants of NJIT's Enterprise Development Center, now known as VentureLink. They have since developed prototypes in the university's Makerspace. "The rapid, inexpensive production of our syringe rod and syringe clip in the Makerspace allowed us to show prototypes to potential buyers and investors without long waits and large expense," noted Cooperman.
To date, they have obtained a dozen U.S. and foreign patents, including a version of their invention that includes the sensor as a replacement for the syringe rod itself that can be included as part of the pre-filled syringe manufacturing process.
The inventors are interested in saving lives, but also in averting waste in the industry by identifying doses that have not reached excessive temperatures, despite ambient readings.
"If medications are momentarily exposed to a high or freezing temperature, an ambient sensor would register them as damaged and they would be returned. But this might be a false positive, as the medication, which might be in a 10 ml. vial, may not have changed significantly," Geissler says. "This is not a good outcome for the supplier."
About New Jersey Institute of Technology:
One of only 32 polytechnic universities in theUnited States, New Jersey Institute of Technology (NJIT) prepares students tobecome leaders in the technology-dependent economy of the 21st century. NJIT'smultidisciplinary curriculum and computing-intensive approach to educationprovide technological proficiency, business acumen and leadership skills. NJITis rated an "R1" research university by the Carnegie Classification®, whichindicates the highest level of research activity. NJIT conducts approximately $170million in research activity each year and has a $2.8 billion annual economicimpact on the State of New Jersey. NJIT is ranked #1 nationally by Forbes for the upward economic mobility of its lowest-income students and is ranked 53rd out of more than 4,000 colleges and universities for the mid-careerearnings of graduates, according to PayScale.com. NJIT also is ranked by U.S.News & World Report as one of the top 100 national universities.