As the number of patients infected with meningitis from contaminated steroids continues to rise and Congress focuses its attention on the FDA’s handling of the situation, a federal court in Massachusetts has consolidated 13 lawsuits against the compounding pharmacy. The Judicial Panel on Multidistrict Litigation (JPML) will decide in January whether and where potentially hundreds of cases should be consolidated. (In re: New England Compounding Pharm. Cases, No. 1:12-cv-12052 (D. Mass. Nov. 29, 2012).)
As of Nov. 19, the Centers for Disease Control and Prevention (CDC) has identified 490 patients who contracted meningitis or other infections after being injected with methylprednisolone acetate (MPA), a steroid used to treat swelling and pain. Thirty-four of those patients died. After the first case was reported in Tennessee on Sept. 18, the CDC and FDA confirmed that the MPA, manufactured by Massachusetts compounding pharmacy New England Compounding Center (NECC), was contaminated with the exserohlium fungus, a black mold found in soil.
When the FDA and the Massachusetts health department inspected NECC’s facility, they found sealed vials of MPA with visible black or white foreign matter that later tested positive for bacteria. They also discovered that, among other things, NECC had distributed recalled lots before receiving confirmation that they were sterile, failed to test its sterilizing equipment, let dirt and standing water accumulate near the clean room, and turned off the air conditioning at night, leaving the room humid and ripe for mold. NECC voluntarily recalled all of its unexpired products and surrendered its state license.
FDA and Massachusetts Department of Public Health documents turned over to Congress in preparation for House and Senate hearings show that NECC had a long history of safety violations and warnings but was allowed to continue operating with little oversight. Several state pharmacy boards repeatedly complained to Massachusetts that NECC was soliciting out-of-state prescriptions, selling non-FDA-approved drug compounds, and distributing large batches of compounded sterile products to facilities without requiring a prescription for each patient.
In 2002, the FDA received two reports that patients had suffered dizziness and shortness of breath after being injected with a different NECC steroid solution. It later received three reports of meningitis-like symptoms after MPA injections, which were subsequently found to be contaminated. When the FDA investigated NECC after both incidents, NECC’s owner and managing pharmacist Barry Cadden questioned the agency’s jurisdiction and refused to produce records of its sterilization practices.
After a 2004 inspection into whether NECC was using a non-FDA-approved drug, the FDA waited two years to send a warning letter discussing several violations and specifying that it would take enforcement action if the company didn’t change its practices. But it did not follow up with inspections or enforcement actions. Similarly, Massachusetts threatened to officially reprimand Cadden and put his license on probation, but eventually agreed to only a stayed one-year probation.
The situation has exposed what Sen. Barbara Mikulski (D-Md.) at a recent hearing before the Senate Health, Education, Labor, and Pensions Committee called a regulatory “black hole”: Who is responsible for monitoring compounding pharmacies? States oversee pharmacies, and the FDA oversees drug manufacturers. But some compounding pharmacies fall into a gray area because they essentially make a new drug from existing drugs. When Congress enacted the FDA Modernization Act in 1997, it exempted compounded drugs from much of the FDA’s control. The FDA does not even know the number of compounding pharmacies because they do not have to register with the agency. And when courts attempted to determine the reach of FDA authority over the pharmacies, it produced mixed results.
“The challenge we have today is that there is a patchwork of legal authorities that really oversee the regulatory actions that we can take,” FDA Commissioner Margaret Hamburg told the House Committee on Energy and Commerce. “We have a split circuit court decision . . . [and] an unclear, fragmented legal regulatory framework that makes it very hard to understand how best to exercise enforcement.”
Several congressional members sharply criticized the FDA, noting that it seemed to think the agency had regulatory authority to shut NECC down when it sent the warning letter threatening to do just that.
“Why do we even have the FDA, and why do you have a job, if the FDA can’t stop back-alley, large-scale drug manufacturing that it knows about and writes letters about?” said Sen. Pat Roberts (R-Kan.).
Calling the outbreak a “complete and utter failure” by the FDA and accusing Hamburg of “practicing plausible deniability,” Congressman Cliff Stearns (R-Fla.), joined later by Congressman Joe Barton (R-Tex.) and others, also pressed Hamburg on whether she felt the FDA had the authority to close NECC when it learned of safety violations a decade ago. Some congressional members came to the FDA’s defense, however, arguing that Congress needs to pass clear regulations.
“I express sympathy to you and the FDA because you’re in a no-win situation,” said Congressman Henry Waxman (D-Cal.) to Hamburg. “If we expect you to do more, we better be sure the statutory law gives you enough authority to do your job.”
Safety advocacy group Public Citizen has called on the FDA to reinspect 16 compounding pharmacies to which it has issued warning letters since 2003, noting that in each case, the agency “identified activities that allegedly crossed outside the bounds of traditional compounding and into drug manufacturing.” Five letters mentioned injuries or deaths associated with contaminated dextrose injections and eye infections linked to contaminated Avastin.
A fight is also brewing in the courts, where dozens of cases have been filed across the country. Several plaintiffs have requested that the JPML consolidate the suits in Minnesota federal court, while others argue that Massachusetts is the proper venue. Meanwhile, Judge Dennis Saylor IV in Massachusetts district court said that although he was aware that the JPML has scheduled a January hearing, “[a]t least at this stage, common questions of fact and law exist, and coordination of these cases will reduce duplication, mitigate potential conflict, and ensure conservation of resources on behalf of all parties and the court.”