Continuing critical “drug shortages remains high and that providers experience challenges responding to drug shortages without adversely affecting patient care,” said the report of a new federal audit.
Although “the number of newly reported shortages has recently declined, due to ongoing shortages that began in prior years, the number of active shortages has increased steadily since 2007 and remains high,” the Government Accountability Office (GAO) said. “The number of active shortages each year almost tripled between 2007 and 2012 from 154 in 2007 to 456 in 2012.”
Many of the shortages involved generic sterile injectable drugs, GAO found. “Specifically, based on our review of the characteristics of a subset of critical drug shortages,” the federal auditor said, “we found that 44 percent of the 219 critical shortages involved generic sterile injectable drugs. Further, four therapeutic classes -- anti-infective, anesthetic and central nervous system, cardiovascular, and nutritive -- comprised 53 percent of critical drug shortages.”
From 2007 through 2011, the number of drug shortages reported increased each year, with a record 255 shortages reported in 2011.
“Faced with this continuing problem, provider association representatives identified challenges in responding to drug shortages without adversely affecting patient care,” GAO reported. “Provider association representatives told us that a number of the challenges that we reported in 2011 were still relevant for their members. Providers may be challenged by delays in or rationing of care, difficulties finding alternative drugs, risk associated with medication errors, higher costs and reduced time for patient care.”
GAO also “found that quality problems resulting in supply disruptions and constrained manufacturing capacity were frequently cited as the immediate causes of recent drug shortages. We determined that the most frequently cited immediate cause of a drug shortage was when a manufacturer halted or slowed production after a quality problem was identified, resulting in a supply disruption. These supply disruptions were linked to, among other things, such problems as bacterial contamination or the presence of glass or metal particles in drug vials.”
But “Although quality problems were a frequently cited issue,” GAO concluded that “there was not complete agreement as to whether quality problems were always the primary trigger for the supply disruptions that cause shortages, with two studies and three manufacturers suggesting that changes in Food and Drug Administration [FDA] inspections of manufacturing establishments also played a role.”
GAO said it “identified a number of additional factors that can cause supply disruptions and ultimately result in shortages, such as permanent product discontinuations or the unavailability of raw materials.” But its “analysis of FDA data and interviews with representatives of drug manufacturers [also] suggested that these factors play a relatively small role overall.”
GAO said “Constrained manufacturing capacity limits other manufacturers’ ability to respond to supply disruptions” and that “there are few generic sterile injectable manufacturers overall, and the existing manufacturers are producing a large number of drugs. For a variety of reasons, these manufacturers have little flexibility to increase production in existing facilities or move production to alternative facilities.”
“In addition,” GAO found, “half of the studies we reviewed suggested that the immediate causes of drug shortages, such as quality problems, are driven by an underlying cause that stems from the economics of the generic sterile injectable drug market. However, the studies that cited underlying causes did not all focus on the same underlying cause. The potential underlying causes cited in the literature were that competition in the generic drug market focuses primarily on price; the possible role of group purchasing organizations; and a change in Medicare Part B reimbursement policy. The studies that cited these underlying causes generally suggested that such causes led to low profit margins, which limited infrastructure investments or led some manufacturers to exit the market. Manufacturer representatives had mixed views on the potential underlying causes we identified in the literature.”
GAO said the “FDA has prevented more potential shortages and improved its ability to respond to shortages since” it first investigated this problem in 2011.
“Based on our analysis of FDA data from January 2011 through June 2013, FDA was able to prevent 89 potential shortages in 2011, 154 potential shortages in 2012 and 50 potential shortages through June 2013. This is more than the 35 potential shortages we found that FDA prevented in 2010 and the 50 prevented through June 2011.”
FDA officials told us that the Food and Drug Administration Safety and Innovation Act (FDASIA), enacted in July 2012, requirement that manufacturers notify FDA in advance of a potential shortage allowed FDA to employ various steps to prevent or resolve shortages sooner.
Until a few years ago, FDA’s Drug Shortage Staff (DSS), which coordinates the agency’s activities to prevent, alleviate and resolve shortages, lacked sufficient authority to respond to shortages. At that time GAO “recommended that FDA strengthen its response and suggested that Congress consider establishing a requirement for manufacturers to report potential or actual supply disruptions to FDA.
The FDASIA was enacted in July 2012 to provide FDA new authorities to address drug shortages and assigned the agency new responsibilities. It also mandated GAO to update its auditing and investigating drug shortages.
GAO said “When FDA is informed of a potential shortage in advance, it may take steps to prevent the shortage, such as providing assistance to the manufacturer to address manufacturing problems … For example, it may offer feedback on a manufacturer’s proposed approach to responding to quality concerns. In addition, FDA can expedite the review of a drug application or can expedite inspections once remediation to address quality problems has been completed.”
But while there are numerous steps that the FDA can take to address a shortage, it “cannot require manufacturers to start producing or continue producing a drug,” GAO pointed out, adding that FDA “also cannot require manufacturers to maintain or introduce manufacturing redundancies in their establishments to provide them with increased flexibility to respond to shortages.”
“In determining how to respond to a shortage, FDA takes steps to assess whether a drug is medically necessary, defined as any drug that is used to treat or prevent a serious disease or medical condition for which there is no other adequately available drug that is judged by medical staff to be an appropriate substitute,” GAO said.
FDA officials said they take steps to address shortages of both medically necessary drugs and non-medically necessary drugs, though they give priority to shortages of medically necessary drugs.
GAO further found that FDA “lacks policies, procedures and specific training materials related to management and use of its existing drug shortage database,” and that “this lack of documentation may limit the agency’s ability to communicate proper use of the existing and new databases to staff and could also ultimately lead to inconsistencies in the use of the database.”
“The lack of policies and procedures is also inconsistent with internal control standards for the federal government, which state that agencies should have controls over information processes, including procedures and standards to ensure the completeness and accuracy of processed data,” GAO said.
In addition, GAO “found that FDA has not conducted routine analyses of its existing drug shortage database to identify, evaluate and respond to the risks of drug shortages proactively. Again, according to the internal control standards for the federal government, agencies should comprehensively identify risk through qualitative and quantitative methods, including data collected in the course of their work. We determined that FDA currently uses data on an ad hoc basis to respond to specific shortages as opposed to using the data to identify trends or patterns that may help it predict and possibly prevent shortages. By only using the database to respond to individual shortages as they occur, FDA is missing opportunities to use the data proactively to enhance the agency’s ability to prevent and mitigate drug shortages.”