Even though reducing waste in health care is a top priority, analysts have missed the waste that can be created when expensive infused drugs are packaged containing quantities larger than the amount needed, according to a new study by researchers at the Memorial Sloan Kettering Cancer Center. The authors call for an end to contradictory regulatory standards in the U.S. that allow drug manufacturers to boost profits by producing single-dose vials containing quantities that increase leftover drug.
Waste is particularly prevalent for cancer drugs for which the dosage is based on a patient’s weight or body size and that come in single-dose packages. These drugs must be either administered or discarded once open, the authors note, and because patients’ body sizes are unlikely to match the amount of drug included in the vial, there is nearly always some left over.
“The leftover drug still has to be paid for, even when discarded, making it possible for drug companies to artificially increase the amount of drug they sell per treated patient by increasing the amount in each single-dose vial relative to the typically required dose,” the authors point out.
The study, published in BMJ, examined the top 20 cancer drugs that are dosed by body size and packaged in single-dose vials in the U.S. (based on 2016 projected sales), which collectively account for 93% of all sales of such drugs in this country. The authors calculated the total amount of leftover drug and resulting 2016 U.S. revenues for each therapy.
The total U.S. revenue from these drugs was estimated to be $18 billion in 2016, with 10% ($1.8 billion) from discarded drug. The extent and cost of leftover drug varied according to market size and available vial sizes. For example, in 2016, the authors estimated that 7% of $3.9 billion in sales for rituximab (Rituxan, Genentech) will be on discarded drug, totaling $254 million, whereas 33% of $697 million in sales for carfilzomib (Kyprolis, Onyx Pharmaceuticals) will be on discarded drug, totaling nearly as much ($231 million).
The proportions of drug left over varied from 1% to 33%. Between these extremes were drugs such as bevacizumab (Avastin, Genentech), which comes in 100-mg and 500-mg vials, and ipilimumab (Yervoy, Bristol-Myers Squibb), which comes in 40-mg and 100-mg vials. Approximately 9% and 7% of these drugs, respectively, are left over, the authors found. But small percentages can still lead to large dollar amounts. According to the authors, the October 2015 Medicare Average Sales Price files show that a dose of ipilumumab might cost $29,000, meaning that the 7% left over would generate an additional $2,000 in revenue for the company for each vial sold.
The authors illustrated the effect of different approaches to packaging for single-dose vials by comparing bendamustine (Treanda, Teva Pharmaceuticals) and bortezomib (Velcade, Millennium Pharmaceuticals). Bendamustine is sold in an array of single-dose vials (25, 45, 100, and 180 mg) that can be combined to reach its recommended leukemia dose of 100 mg/m2 almost precisely. Vial combinations cover every 5-mg interval across the typical adult dose range of 110 mg to 310 mg, with the exception of 130 mg and 155 mg. The authors calculated that only 1% of bendamustine is wasted. The multiple myeloma drug bortezomib, on the other hand, is available in the U.S. only in a 3.5-mg vial, much larger than the average required dose, which the authors calculated to be 2.5 mg, based on the drug’s dose of 1.3 mg/m2 and the average weight of a cancer patient. The authors estimated that 27% to 30% of bortezomib sales in the U.S. are related to leftover drug, totaling $309 million. Bortezomib is sold in smaller 1-mg vials in the United Kingdom.
The authors point to pembrolizumab (Keytruda, Merck) as another example of how vial sizes can enhance pharma companies’ revenues. When pembrolizumab was initially approved in the U.S. in September 2014, it was sold in 50-mg vials (as a powder that was reconstituted into a liquid). But in February 2015, the manufacturer introduced a larger 100-mg vial (as a liquid) and stopped distributing the 50-mg vials to the U.S. market. Five months later, in July 2015, pembrolizumab was approved in Europe, where it is now sold in the smaller 50-mg vials as a powder.
Although the authors focused on cancer, the problem of mismatched single-dose vials and doses is not unique to that disease, they noted. The asthma drug omalizumab (Xolair, Genentech/Novartis), for example, has approved doses in 75-mg intervals, but only 150-mg vials are sold in the U.S., even though the drug has an approved 75-mg vial size. Another example is infliximab (Remicade, Janssen Biotech), one of the largest-selling drugs in the U.S., which is available only in 100-mg single-dose vials. Infliximab is dosed based on body size, and the authors estimated that its packaging generates approximately $500 million in additional revenues from leftover drug.
The authors concluded: “Regularly and systematically discarding expensive drugs is antithetical to efforts to reduce spending on health care services that provide no value. Policy makers should therefore explore approaches that would reduce or eliminate paying for leftover drug. Current regulatory standards could be viewed as contradictory, or at least as ambiguous.”
Source: BMJ; March 1, 2016.