My ARC colleague Janice Abel told me a story recently that is making me question the safety and efficacy of prescription drugs purchased online.

Janice was visiting her stepfather who had been away from home for a long weekend. When he returned and went out to the mailbox, on a hot summer day in the 90s, he saw that his diabetes medicine had arrived, but the ice pack in the package had melted. He asked Janice if the drugs were still okay, so she tracked the shipment online to see when it was delivered. It had been delivered five days earlier. Janice suggested that he call the online pharmacy and explain the situation. He did and the customer service person told him not to worry about it, the drugs were probably still fine. Janice then read the drug insert which stated the drug was only approved up to 84 degrees. Janice had her stepfather call the online pharmacy back to relay this information to them, along with the fact that the medication looked unusually cloudy. This time he managed to convince the pharmacy to send him a new shipment without charge.

Janice is our principal analyst focused on the Life Sciences industry, and she has written about cold chain issues for ARC. This is why she had her stepfather push the issue with the online pharmacy, because she knew that some biologic drugs can be rendered useless if they fall outside their specified temperature range. There is a reason why drugs are tested and approved by the U.S. FDA for efficacy within a specific temperature range.

I went back to some of Janice’s cold chain writings (here and here, available to ARC clients only) and discovered that the number of temperature-sensitive products, such as vaccines, insulin, biologics, specimens, and blood products, is on the rise. Keeping drugs in a desired temperature range when they are inside a factory or warehouse is hard enough. But now think of these drugs sitting at loading docks while trucks are loaded and unloaded, or sitting in a hot mail box for hours or days, which happens with online pharmacy supply chains.

The cold chain is also getting more complex because we are dealing with not just domestic cold chains, but regional and international logistics as well. For example, the pharmaceutical supply chain in Europe is particularly complex. In virtually any supply chain, you have manufacturers, distributors, and retailers. In the European Union there is something known as “parallel trade” that allows wholesalers in different nations to trade drugs in order to allow more favorable pricing for consumers (too bad this idea was not discussed in the healthcare reform debate going on here in the U.S.).

At the global level, clinical trials are increasingly being conducted in third world countries, which typically have relatively poor logistics infrastructures. Pharma companies are doing this to cut costs out of the development process.

Certain technologies can help companies effectively manage a cold chain. At the low end, there are temperature indicators that can track whether a shipment has gone outside the desired temperature range. However, this is a reactive rather than a proactive approach. The International Society for Pharmaceutical Engineering (ISPE), a not-for-profit association for pharmaceutical manufacturing professionals, has written about using RFID and GPS systems linked to temperature sensors to proactively manage a reliable cold chain. ISPE also highlights the use of passive coolers made out of Phase Change Materials (PCMs). Unlike conventional shipping materials, when PCMs reach a certain temperature, they change phase (either melt or solidify) and absorb or release energy (hot or cold) at an almost constant temperature. My assumption, based on Janice’s story, is that PCM packaging is more the exception than the rule.

ISPE is in the process of developing cold chain good practice guidelines for its manufacturing subscribers. Janice is one of the industry experts ISPE has asked to review the guidelines. In developing these guidelines, ISPE will have to wrestle with two key questions: how far down the extended supply chain manufacturers should track their products (to distributors? to drug stores? all the way to the mail box?), and how granular should that tracking be (one-step recall capabilities or true end-to-end traceability?).