Magazine
A Cold Chain Parable
Cold chain can be a matter of life and death
By Kevin O'Donnell
There was a woman from Pleasanttown, who passed away late last year after a long bout with cancer. Her name was Maureen. She was 33 years old.
Maureen was the type of person we all like to call a friend — compassionate, witty, and intelligent — unselfishly giving of her time and talent. She was a devoted mother and a loving, supportive wife. She took good care of herself and maintained an active and healthy lifestyle. She didn’t smoke, watched what she ate and went to yoga class regularly. But cancer is capricious and plays no favorites. Although she had not been feeling well, she was never one to run to a doctor every time she was feeling out of sorts. As a result, Maureen’s illness went undiagnosed and untreated longer than it should. By the time her diagnosis was confirmed, her ovarian cancer was Stage III. Still, she kept her spirits high and retained her positive attitude.
Maureen was encouraged to learn that second and third generations of chemotherapies, called cytotoxics, had become integral to managing the disease, and were key reasons for an upward trend for five-year survival rates of ovarian cancer between 1975 and 1997 in the U.S. (improving at a compounded annual growth rate of 1.2%).
After a successful surgery to remove the cancerous tumor on her ovaries, Maureen had several options for treatment. She discussed these at length with her doctors and also researched on her own. She opted for a platinum-based therapy, a combination of two drugs that, when taken together, are considerably more effective than taken alone. This regimen has been the mainstay for treatment of ovarian cancer. She began her chemotherapy infusions and everyone was optimistic about her prognosis.
Maureen had a friend who once worked for a major drug company. She assumed that his experience somehow qualified him as an expert on drugs: everything from how they worked to their potential side effects. But he was an engineer, not a pharmacologist. The details on how drugs did the marvelous things they did were not his area of expertise. His expertise was in protecting drugs from adulteration until they reached the patient. That was some challenge, for it was well known in Pleasanttown and beyond that a drug was deemed adulterated by the FDA “if the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.” (FD & C Act Chapter V, Sect. 501 Sub-chapter A, (2)(B).)
Adulterated drugs are not something most people think about or even question. Trying to be as supportive as he could, Maureen’s friend decided to research the pharmacology of the drugs on his own. Beyond their astonishing complexity and effectiveness, what immediately caught his attention was that both drugs in her therapy were temperature-sensitive. One, a lyophilized powder, required 2-8° C storage, the other, a solution, was labeled “store above freezing and below 25° C.” This he knew, placed the drugs at a high risk for adulteration, and special handling and storage was critical.
Maureen responded very well to the treatment. The drugs were administered at one of the nations' leading oncology hospitals, near her home in Pleasanttown. She received a two-day intravenous dose every three to four weeks, and suffered with the usual contaminants of her therapy afterwards — nausea, hair loss, fatigue, and some blood test abnormalities — but nothing beyond the norm. She was closely monitored and her doctors were very careful to continue her treatment protocol only after tests demonstrated her platelet count, renal output, liver function, and her visual and auditory functions were within acceptable ranges.
After Maureen’s third treatment, however, things changed drastically. She no longer responded as she had previously. Her doctor said her renal and blood tests were not showing the same levels of response to the combination of cytotoxics as they had in the past. When she asked him why, he responded with a litany of possibilities. Soon afterwards Maureen’s health began to falter and the doctor was telling her and her husband that the time had come to concentrate on palliative treatment, aimed at ensuring a better quality end-of-life, rather than put their hopes in a curative treatment.
As her family and friends watched the insidious disease progress and take the life from her, Maureen’s friend did some further investigating. He could not get out of his mind the doctors comment that “her renal and blood tests were not showing the same levels of response to the combination of cytotoxics as they had in the past.” Had the drug somehow been adulterated? His experience told him that if this were to happen, it would most likely occur during the distribution process. This was an area he knew well and where he focused his attention.
Maureen’s friend contacted individuals he knew at the manufacturing facilities where the drugs Maureen had been taking were made. Both companies were among the best in their field and had a longstanding reputation for producing, distributing and maintaining the highest quality medicines. One of the drugs he noted was manufactured overseas and imported to the U.S. Working with associates in the manufacturer’s international logistics department, Maureen’s friend was able to determine the drug's point of entry into North America. The goods were received at an airport with a notorious reputation for improper handling and storage procedures. Their on-airport cold storage was shared among several airlines, including the airline contracted to lift the particular chemotherapy drug administered to his friend, Maureen. The cold room was also used to store all sorts of things: fresh fish, plants, fruits and vegetables, meat, and cut flowers, all of which had their own set of temperature requirements. The most frequent user of the cold room at this particular airport happened to import roses by the planeload from Fleurland. The importer paid extra to have the thermostat of the cooler at the airport set at minus 2° C to keep his roses from blooming. The airport was happy to accommodate him because all the roses in Pleasanttown were imported from Fleurland and it meant the airport stayed busy and it boosted their revenue. The importer was also very pleased because getting the airport to set the cooler thermostat at minus 2° C prevented his roses from wilting, increased his blooms’ longevity, and brought him greater profit.
As was often the case, other temperature-sensitive freight was stored along with the roses at minus 2° C, including drugs requiring 2-8° C storage and “store above freezing and below 25° C.” Exposure to minus 2° C temperature can be disastrous in such instances, and freezing was known to do this to a certain platinum-based therapy taken by Maureen from Pleasanttown.
Whether or not the therapy Maureen was taking was exposed to freezing temperatures that rendered it ineffective cannot be determined, but it is a possibility. And whether this attributed in whole or in part to Maureen’s premature and horrible death will never be known. There are a multitude of possible reasons for her failing to respond to her treatment. But in her friend's mind there will always be doubt.
It seems particularly sad and cruel that a woman with Maureen’s vitality and zest for life should be taken at such a young age, leaving behind a grieving husband and twin daughters too young to comprehend why their mother was never coming back. These sentiments were repeated over and over by the hundreds of relatives and friends who attended Maureen’s funeral. It was a cold and rainy day in Pleasanttown when Maureen was laid to rest.
Maureen’s friend couldn’t help but notice that the beautiful imported roses on top of her coffin were just beginning to bloom.
