With the Annual Meeting of the American Society of Clinical Oncology this past week came a wave of news stories about cancer and cancer treatment. Frank Pasquale highlights a disturbing warning issued by oncologists at the meeting, that “cancer medicines desperately needed by sick children and adults are in short supply, undermining the ability of U.S. doctors to administer treatments.” Supplies of other medicines are running short, too, including treatments for anaphylactic shock, attention deficit hyperactivity disorder, cardiac arrest, cystic fibrosis, and infertility.
Writing for the AP, Lauran Neergaard reports that “[t]he problem of scarce supplies or even completely unavailable medications isn’t a new one but it’s getting markedly worse.” According to Lancet Oncology, there were a record 211 drug shortages in 2011, up from 166 in 2009, 149 in 2008, 129 in 2007, and 70 in 2006. Neergard adds that “another 89 drug shortages have occurred in the first three months of this year[.]”
Most of the medicines that have run short are sterile injectable drugs, which are complex and time-consuming to manufacture. (The anesthesia drug sodium thiopental which I blogged about here falls into this category.) And, most, or even all, of the shortfall drugs are no longer subject to protection from a patent or Food & Drug Administration-administered exclusivity period, so the innovator firms that developed them are subject to competition from generic manufacturers. The resultant lower prices and slimmer profit margins mean that, in the words of leading oncologist Dr. Richard Schilsky, the manufacturers’ return on investment is “pretty low.”
Among the reasons cited for the rise in drug shortages are the inherent challenges of manufacturing sterile injectable drugs, the low return on investment facing generic manufacturers, which has led the number of manufacturers of any given generic drug to dwindle, drug company mergers, which can result in the discontinuation of one of two similar products, the time it takes the FDA to approve applications to make manufacturing changes, for example a change in the source of a drug’s active ingredient, and the failure of the FDA to act expeditiously in investigating manufacturing problems and clearing plants to resume production once the problems have been resolved.
The Preserving Access to Lifesaving Medications Act, introduced in February by Senators Robert Casey and Amy Klobuchar, would require manufacturers to notify FDA “of a discontinuance, interruption, or other adjustment of the manufacture of the drug that would likely result in a shortage of such drug[.]” Per Lauran Neergard, the FDA “was able to prevent 38 close calls from turning into shortages last year by speeding approval of manufacturing changes or urging competing companies to get ready to meet a shortfall.” The FDA has even permitted (temporarily) the import of medicines approved outside the United States when necessary to mitigate shortages.
Participants in a Drug Shortages Summit convened late last year by the American Society of Clinical Oncology and others recommended that additional legislative and regulatory reforms be explored, ranging from providing incentives to manufacturers in exchange for a guarantee that they continue producing critical drugs, to charging manufacturers fees to fund expedited FDA review of applications for permission to manufacture generic drugs, to requiring manufacturing redundancies (e.g. that more than one source for a drug’s active ingredient be identified) as a condition of approval. Interestingly, while some participants in the Drug Shortages Summit argued that products liability exposure could cause companies to withdraw drugs from the market, the manufacturers who attended denied this, calling the decision “multifactorial.” There is evidence to support the manufacturers’ claim. As I discussed here, in late 2004, after Chiron Corporation announced that it would not be able to provide flu vaccine for the United States market that year due to manufacturing issues, Congress brought the flu vaccine into the Vaccine Injury Compensation Program fold. Unfortunately, liability relief did not result in an increase in the number of manufacturers in the flu vaccine market. Targeted reforms like those that the Summit participants recommend be explored seem more likely to be effective at ensuring a steady, reliable supply of vital medicines.