Debate over temperature monitoring during drug shipment intensifies

By Anne Blythe

As periods of extreme heat become more frequent in North Carolina and across the country, and more heat records are broken around the world, policymakers are paying greater attention to the health impacts of climate change.

The National Integrated Heat Health Information System released the first national heat strategy earlier this month, acknowledging the threat of rising temperatures to public health and the need to develop plans and strategies to mitigate the negative impacts of the “leading cause of weather-related death”.

“Extreme heat is not only an environmental crisis, it also poses a serious threat to our public health – and communities across the country are struggling to respond,” said Federal Health and Human Services Secretary Xavier Becerra in unveiling the plan.

A related issue that has only recently received attention is the impact of extreme heat on prescription drugs during transport – particularly when these drugs are delivered by mail.

The New York Times highlighted the issue earlier this month.

Jay Campbell, executive director of the North Carolina Board of Pharmacy, told NC Health News he has received a flood of calls about the issue recently.

“This appears to be primarily a problem with mail-order pharmacies,” Campbell said.

Why not add temperature trackers?

State law requires pharmacies outside of North Carolina that ship, mail or deliver prescription drugs approved by the U.S. Food and Drug Administration to register with the state board of pharmacy and ensure that they are staffed by a pharmacist who meets state licensing requirements.

These pharmacies are responsible for the safe transport of the drugs, but a study conducted in Journal of the American Pharmacists Association raises questions about temperature fluctuations during transport. Researchers shipped packages with data loggers inside between New Jersey, California and Tennessee at different times of the year and found that the packages stayed in the appropriate temperature range only about a third of the time.

Extreme temperatures can affect the effectiveness of medications, whether by evaporating liquid, changing aerosol pressure, or altering other components of medications.

The United States Pharmacopoeia, a 200-year-old independent organization whose goal is to build confidence “in the supply of safe, high-quality medicines,” recommends that medicines should generally be stored at temperatures between 20 and 25 degrees Celsius, with room for temperature fluctuations where the temperature can briefly drop to 15 degrees Celsius or rise as high as 32 degrees Celsius.

Some drugs, such as diabetes medications that can become cloudy, are more likely to break down than others. Other protein-based drugs, such as the extremely popular arthritis drug Enbrel, are also at risk from high temperatures, as these can break down the proteins. Even test strips for diabetic blood sugar testing and other home blood tests can break down in the heat.

Campbell is often asked how enforcement works in cases where a drug has been damaged. People can contact their pharmacist. They can also file a complaint with the Board of Pharmacists. But other than cloudy insulin, evidence of such deterioration is not always clear. Nor is it always possible to determine where the damage occurred.

Even if pharmacies take all necessary measures to keep the temperature of medications within the correct range during transport, it can happen that a package is thrown into a dark mailbox or left in front of a door and sits in the blazing sun for hours before the recipient comes home from work or realizes that the package is waiting for them outside.

Proponents of reform say packages containing temperature-monitoring devices could alert recipients to any anomalies en route.

Federal law does not require such devices, and North Carolina law, Campbell said, prevents the state from enacting more restrictive regulations than “federal laws or regulations governing the delivery of prescription drugs by mail or by a carrier.”

“In my opinion, the requirement that temperature-sensitive medicines have some kind of warning on their packaging also makes sense for public safety reasons,” Campbell said.

In order to require the use of temperature monitoring devices, a change in the law would be necessary.

Pharmacy benefit policies are part of the mix

Penny Shelton, executive director of the North Carolina Pharmacists Association, said her organization has spent the past few years focusing on a bill that would revise pharmacy benefit manager regulations in state law.

In recent years, Shelton said, the state has been losing pharmacies. Since 2022, a hundred pharmacies have closed in North Carolina, she added. This trend, she believes, is related to the issue they want lawmakers to pay more attention to.

The House of Representatives unanimously passed HB246 in April 2023, but the proposal has stalled in the Senate.

While this law is not directly related to transporting medications in extreme heat, it may affect part of the problem. Health insurance companies contract with, or in some cases own, pharmacy benefit managers. The managers are intermediaries who manage the pharmacy benefits of a person’s health insurance plan. This often leaves patients with little choice about where to get their medications. Many pharmacy benefit managers only offer mail order, a practice known as “steering.”

“It’s not that we don’t think it’s important,” Shelton said of temperature-monitoring devices in drug packaging. “We do. But we think patients should have a choice when it comes to their pharmacy. We’re fighting for a number of legislative issues.”

Pharmacy benefit managers played a role in thwarting an effort in Oklahoma several years ago to require pharmacies to keep medications in certain temperature ranges during transport. The effort was abandoned after lobbyists and the Pharmaceutical Care Management Association, which represents benefit managers, opposed the proposal.

The association’s vice president of state affairs and director of state regulatory and legal affairs claimed in a letter to the executive director of the Oklahoma State Board of Pharmacy that the proposal was “not based on scientific evidence and knowledge” and appeared to be “based on speculation and an attempt to solve a perceived problem.”

“Local and off-site pharmacies undergo rigorous material and process testing to ensure the integrity and stability of medications are maintained,” the association’s officials said in their letter.

Specific tracking

As the debate over transport temperatures gains more attention, some in the pharmaceutical industry are focusing on cold storage facilities that can store temperature-sensitive vaccines, tissues, compounds and other biopharmaceutical therapies.

Alcami Corporation recently expanded the customizable cold storage options at its new Garner facility. In a recent video call, David Vogt, senior director of pharmaceutical storage at the facility, explained to NC Health News how the company ensures that stored products are kept at appropriate temperatures.

“Our facility here is essentially a large warehouse where we store both at normal room temperature and under very specific controlled temperature conditions – particularly cold,” said Vogt. “So we store everything here from refrigerated (at 5 degrees Celsius) to minus 20 degrees Celsius, minus 40 degrees Celsius, minus 75 degrees Celsius, to cryogenic storage in liquid nitrogen.”

Whether traditional small molecules or biologically based products – such as those used in newer gene therapies – temperature can have a huge impact on the quality and efficacy of these products if they are not continuously stored under appropriate conditions, Vogt said.

“For us here at Garner, our core business is to ensure that we work with our pharmaceutical and biopharma customers to ensure the safety and quality of the products they entrust us to store,” said Vogt.

Normally, he said, most cold products are transported to the plant by a suitable truck.

“The truck is actually validated and mapped to make sure those conditions are met throughout the entire transport of material,” Vogt said. “But on top of that, we equip all of our shipments with temperature trackers, that’s what we call temperature monitoring devices. That gives us real live data to see how the truck and shipment performed from point A to point B.”

Although the warehouse was not built because of the extreme heat that is becoming more common due to climate change, Vogt acknowledged that the Garner facility is only one piece in the supply chain puzzle.

“Our piece of the puzzle is actually being able to maintain the quality of your product under the conditions in which it needs to be stored,” Vogt said. “We make sure that the movement of the material from point A to point B is controlled so that it is protected from the extreme heat that we are exposed to.”