We have covered drug shortage issues numerous times, including their impact on the healthcare system and patient care. Previous government studies have concluded that its own regulatory agencies have failed to address the problem, and in some cases may be responsible for furthering shortages.
The Food and Drug Administration (FDA) explains that shortages of pharmaceuticals can happen for a variety of reasons including manufacturing issues, quality control problems, and production delays. This puts patient’s lives at risk, as illustrated by the many recent stories on drug availability. In one example, the bladder-cancer drug BCG is currently sold by just one company, Merck, and they do not expect to produce enough of the medication until next year. Hospitals used to get around 20 vials of medicine a week, now one says it is limited to receiving six every two months. With 16,000 deaths projected this year alone, bladder cancer is the fourth-most common type of disease in men with around 76,000 new cases estimated this year among both men and women. The standard treatment for aggressive early-stage bladder cancer is BCG, a medication patients often need for months or even years.
GAO study and Congressional hearing
According to a recent report from the Government Accountability Office (GAO), the U.S. Drug Enforcement Agency (DEA) and the FDA should work together more closely to prevent shortages of prescription medications containing controlled substances, and the DEA should improve its process for authorizing quotas of the controlled substances used in these drugs. The report was requested by members of Congress, where there is bipartisan interest in combating increasingly serious drug shortages. Sen. Charles Grassley (R-IA) and Sen. Sheldon Whitehouse (D-RI) commissioned the GAO report in 2012, and soon, Grassley and Sen. Dianne Feinstein (D-CA), the leaders of the Caucus on International Narcotics Control, are scheduled to hold a hearing on the report's findings. The initial hearing was scheduled for April 14, but was postponed. A new date for the hearing has not yet been selected.
The GAO study looked at: (1) the trends in drug shortages; (2) the effect on patients and providers; (3) DEA’s administration of the quota process; and (4) coordination between DEA and FDA to prevent and mitigate shortages. The GAO analyzed data from 2001 through 2013 from the University of Utah Drug Information Service, which is generally regarded as the most comprehensive source of drug shortage data, and from 2011 and 2012 from YERS/QMS, which is the official record for the quota process. The GAO interviewed officials from DEA, FDA, organizations representing patients and providers, and drug manufacturers. In its conclusion, the GAO recommended the DEA and FDA take several actions to improve their management of the quota process. HHS agreed with the recommendations, although the DEA raised objections to the report.
Specifically, the GAO recommended that the DEA Administrator establish controls, including periodic data checks, to ensure that the Year End Reporting and Quota Management System (YERS/QMS) data, which is the official record of the quota process, accurately reflects both manufacturers' quota submissions and DEA's decisions. The GAO found that DEA’s lacking systematic data checks is “inconsistent with federal standards for internal control, which calls for agencies to have appropriate control activities in place, such as periodic data checks, to ensure that the data used by the agency for decision making are accurate.” The DEA told GAO that it does not monitor data from YERS/QMS to assess the administration of quotas, and without such it will be unable to evaluate its responses to manufacturers’ quota applications or understand the nature of its workload.
Additionally, the Administrator should establish measures for the agency related to quotas and ensuring an adequate and uninterrupted supply of controlled substances for legitimate use. Without these standards, the DEA does not have sufficient information to make decisions to manage its programs effectively. The quotes should be established along with internal policies for processing quota applications and setting aggregate, annual, and supplemental quotas to ensure that staff conduct these activities consistently and in accordance with the agency's regulations. DEA officials cited staffing problems for their failure to meet regulatory timeframes for the proposal and establishment of quotas.
The GAO strongly recommended DEA and FDA establish formal policies and procedures to facilitate coordination, including a specific timeframe in which DEA will respond to FDA request to expedite shortage-related quota applications. Interestingly, the Food and Drug Administration Safety and Innovation Act (FDASIA) already requires DEA and FDA to coordinate where additional quota may be needed to address a shortage of a drug containing controlled substances. The GAO report states that the agencies lack compatible policies and procedures and disagree on what constitutes a shortage of controlled substances.
Finally, the GAO recommended the DEA and FDA quickly update their MOU (memorandum of understanding) regarding steps each will take to reduce drug shortages. It further calls on the DEA and FDA to outline the type of information they will share and the timeframe for doing so in response to current or potential drug shortages.
FDA on shortages
In an April 10 blog post, FDA described how the agency works with its drug shortages team to ensure adequate supplies of FDA-approved drugs in the United States. FDA describes examples of manufacturers obtaining approval for formerly unapproved products, highlighting collaboration between the offices within the agency. FDA states:
Such approvals highlight the strength of collaborations between FDA’s shortages staff, our unapproved drugs team, and the Office of New Drugs. These approvals are crucial for FDA: once a drug is approved, we know what ingredients are in the drug, how it is made, and that it has been shown to be safe and effective for its labeled use. Approval of formerly unapproved products also helps alleviate FDA’s concerns about a potential market disruption or shortage of these drugs, because the manufacturers of approved drugs have invested in a manufacturing process that helps to ensure the drug is produced the same way every single time, lowering the risk for shortage.
FDA further explains if a single manufacturer is the sole maker of a newly-approved product it may result in the drug’s prices being higher than what patients and prescribers paid for an unapproved version of the drug. FDA specifically notes that it “does not factor costs” into the approval of drugs and encourages companies to apply for the approval of generic versions of medication, citing neostigmine, a formerly unapproved drug that now has two approved manufacturers.
The FDA’s blog post does not address one of the more interesting conclusions from the GAO study, which found that disagreements over the official meaning of a “drug shortage” might ironically help facilitate them. According to a report citing the University of Utah Drug Information Service (UUDIS), there was a 47 percent drop in new drug shortages between 2011. In 2015 the UUDIS was tracking 301 active shortages, an increasing trend according to a 2014 GAO report. However, during the same time period, FDA claims drug shortages declined. While UUDIS defines a shortage as a supply disruption that affects how a pharmacy prepares or dispenses a drug product or that influences patient care when prescribers must use an alternative agent, FDA’s definition considers whether the combined supply from all manufacturers in a specific drug market meets historical demand patterns.
FDA’s definition considers the relevant market in which the drug exists, looking at the clinical implications of the supply disruption in question. The agency may question if patients may use another version of the drug containing the same active ingredient. FDA uses third-party market research databases to assess the market share of possible disruptions, then contacts manufacturers of products in the relevant market who generally will voluntarily provide information such as their inventory status, rate of demand (units per month), manufacturing schedules, and any changes in ordering patterns. FDA may conclude that supply meets the historical or anticipated demand. This higher level of information differentiates the FDA drug shortage data from UUDIS, the latter of which will not delist an issue until all presentations or forms of the drug are back on the market.
We will continue to monitor drug shortages, including their impact on the effectiveness of medical treatment in the United States and the government’s response. The upcoming Congressional hearing on the recent GAO report will provide additional insight into potential legislative and regulatory vehicles that may be employed to deal with the current crisis. Clarity and consistency over the definition of a drug shortage could be a topic, if the GAO report is any indication.