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GAO on Drug Shortages: FDA’s Prioritization of Generic Injectable ANDAs is Helping

Posted 13 July 2016 | By Zachary Brennan 

GAO on Drug Shortages: FDA’s Prioritization of Generic Injectable ANDAs is Helping

As the number of new drug shortages has generally decreased since 2011, the US Government Accountability Office (GAO) said that although it cannot establish a causal link, the US Food and Drug Administration’s (FDA) prioritization of reviewing hundreds of applications and supplements during the time period GAO examined helped address some of those shortages.

New drug shortages peaked in 2011, with 257 reported, GAO says in a recently released report, though that number has since fallen off considerably, with 136 new shortages reported in 2015, a decrease of 47% since 2011.

However, since 2012, the number of ongoing shortages (shortages that began in years prior) has remained high, with over 250 ongoing shortages each year from 2012 through 2015 and in 2015, 68% of shortages were ongoing shortages, most of which were for generic sterile injectable drugs.

“The fact that some shortages have lasted 3 or more years suggests that manufacturers and FDA have had difficulty addressing the issues behind these persistent shortages,” GAO cautions. “For example, FDA stated that some drugs have been in shortage for multiple years because manufacturers have been unable to address the issues that led to the shortage or have chosen not to continue producing the drugs.”

FDA Action 

FDA prioritized the review of 383 drug applications and supplements to address shortages from January 2010 through July 2014, GAO says, and 240 (63%) of those priority reviews were for generic sterile injectable drugs. The overwhelming majority of those also were for abbreviated new drug applications (ANDAs), while 4% (17) were for brand-name sterile injectable drugs.

“Our analysis of a subset of those submissions indicates that some were approved before the shortage was resolved,” GAO says. “Although the timing of FDA’s approvals of submissions does not establish a causal link, it could indicate that prioritizing reviews may be a useful strategy in addressing some drug shortages.”

But given that the median approval time for prioritized ANDAs is longer than a year, GAO says that prioritizing ANDA reviews to address drug shortages is not necessarily a strategy for addressing shortages in the short term, but may work for shortages that have persisted across multiple years or recurred multiple times in a few years.

Warning Letters 

Although FDA increasingly issued warning letters across the time period studied by GAO, the percentage of inspections that resulted in warning letters in a given year remained relatively small, the report says.

“One percent of FDA’s fiscal year 2007 inspections of sterile injectable drug establishments resulted in the issuance of warning letters, compared with 5 percent of such inspections in fiscal years 2010 and 2011,” according to GAO.

However, GAO says that FDA officials “disputed the notion that the agency’s issuance of warning letters to establishments found to be out of compliance with manufacturing standards caused shortages” because some shortages are unrelated to manufacturing problems. 

GAO confirms that view, noting that a prior analysis of FDA shortage data found that from January 2011 through June 2013, 30% of shortages were reportedly caused by issues unrelated to manufacturing, but due to increased demand or unavailability of raw materials or other product components.

FDA officials told GAO that during this time frame, inspections of sterile injectable drug manufacturers were often conducted because of reports of problems with particulates, noting a number of voluntary recalls conducted in response to glass fragments in sterile injectable drugs in 2010 and 2011.

“Our analysis of 7 years of FDA data on inspection type does not reveal a clear trend in terms of the relationship between shortages, warning letters, and one indication of potential manufacturing problems—the frequency of inspections with a for-cause component,” GAO added.

Seven manufacturing facilities linked to widespread shortages that received warning letters all had previous indications of difficulty complying with manufacturing standards, GAO says, noting that shortages of sterile injectable anti-infective and cardiovascular drugs in 2012, 2013, and 2014 “were strongly associated with certain factors GAO examined.”

Two of those factors — a decline in suppliers and failure of at least one establishment making a drug to comply with manufacturing standards resulting in a warning letter — “suggest that shortages may be triggered by supply disruptions,” GAO says. “A third factor—drugs with sales of a generic version—suggests that due to relatively low profit margins for generic drugs, manufacturers are less likely to increase production, making the market vulnerable to shortages.”

GAO REPORT: DRUG SHORTAGES Certain Factors Are Strongly Associated with This Persistent Public Health Challenge

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