In response to a congressional committee report holding it largely responsible for drug shortages, the FDA counters that the shortages are beyond its control.
A congressional staff report
issued in June made the case that overzealous regulation by the FDA is largely responsible for the increase in drug shortages over the last several years. Now the FDA has issued a response, arguing that the primary causes of drug shortages are beyond the agency’s control.
In its June 15, 2012, staff report, “FDA’s Contribution to the Drug Shortage Crisis
,” the US House Committee on Oversight and Government Reform drew a connection between an increase since 2009 in the number of warning letters issued by the FDA to manufacturers and the growing drug shortage crisis, especially of generic injectable medications. The report points out that between 2009 and 2010, the number of warning letters sent by the agency increased 42%, from 474 to 673, and between 2010 and 2011, the number increased another 156%, to 1720.
Rather than pinpointing the precise problems with drug manufacturing, the report alleges, the FDA has ordered costly general upgrades to plants, which lead to significant lapses in production. The consequences for supplies of generic injectable drugs, many of which are produced by a limited number of manufacturers, have been particularly severe, according to the report: Four major producers of generic injectable medications— Bedford Laboratories, Hospira Pharmaceuticals, Sandoz Pharmaceuticals, and Teva Pharmaceuticals—have reduced their combined production 30%, from 1 billion units per year to 700 million units per year.
As of February 21, 2012, the report adds, at least 128 (58%) of the 219 drugs on the American Society of Health System Pharmacists’ shortage list were being produced by at least 1 facility undergoing FDA remediation. In addition, the report alleges, there is no evidence that any of the drugs manufactured at any of the facilities undergoing remediation has been associated with any unusual adverse effects. In short, the report argues that the FDA has erred too far on the side of caution, effectively depriving patients of essential drugs when these drugs pose no real threat to patient safety.
In a July 23, 2012, letter
, Jeanne Ireland, FDA assistant commissioner for legislation, responds to these allegations. More than half of drug shortages in recent years, she argues, have been due to manufacturing production problems, including issues related to quality and delays, with the remainder related to business decisions to discontinue products, raw material shortages, loss of manufacturing sites, increased demand, and component problems. “The root causes of drug shortages … lie largely outside of FDA’s purview,” she writes.
The letter notes that the FDA is committed to helping avoid shortages while ensuring that safety standards are upheld. It claims that the FDA helped avert 195 shortages in 2011 and 90 so far in 2012 by using a variety of tools: working with manufacturers to rectify problems without disrupting supply; expediting review of plants; identifying alternative manufacturers of drugs facing potential shortages; helping to implement short-term work-around solutions when required remediation may result in a shortage; and allowing for temporary import of needed drugs.
The letter points out that the major cause for the increase in FDA warning letters since 2009 was the agency’s new authority over tobacco products. Of the 1720 warning letters issued in 2011, it notes, 1040 (60%) related to tobacco products. From 2008 to 2011, as drug shortages increased dramatically, the letter notes, the number of FDA warning letters related to quality deficiencies in manufacture of human drugs or biological products remained more or less steady: 20 in 2008, 34 in 2009, 60 in 2010, and 48 in 2011.
Contrary to the report’s contention that the FDA’s warnings to manufacturers were not based on serious safety concerns, the letter notes the following potential safety risks addressed by warning letters: endotoxin contamination of Teva’s propofol injection emulsion product; presence of metal particles in sterile drugs, aseptic conditions, and underfilled drugs at Ben Venue Labs, the manufacturing arm of Bedford Laboratories; metal particles in several injectable drugs and overfills of vials of liquid morphine up to twice the indicated quantity by Hospira; and crystals forming in injectable drugs at Sandoz, a Novartis company, as well as over 1000 complaints of foreign, stray, and broken tablets in opiate products made by Novartis, indicating potential contamination.
“FDA inspections do not cause firms to have manufacturing or quality problems, which are the root cause of many shutdowns,” the letter concludes. “Where shutdowns occurred, they were in the context of serious, unresolved safety concerns and were not ordered by FDA.”
Previous Pharmacy Times coverage of drug shortages: