April 16, 2013
Internal FDA Documents Gathered During Committee's Six-Month Investigation Reveal that FDA Could Have Acted Sooner Against NECC and Ameridose
WASHINGTON, DC – The House Energy and Commerce Committee today released a majority staff report citing internal documents from the Food and Drug Administration chronicling the agency's numerous opportunities over the years to address warning signs about the pharmacy that produced and distributed the contaminated drugs that led to the deadly meningitis outbreak, the New England Compounding Center (NECC). The outbreak has resulted in 53 deaths and over 700 individuals sickened. In October 2012, the Oversight and Investigations Subcommittee launched an investigation to examine the deadly outbreak and determine whether this tragedy could have been prevented. The investigation revealed what FDA Commissioner Margaret Hamburg did not disclose during the November 2012 hearing: FDA received a litany of complaints about NECC and its sister company, Ameridose, right up until the 2012 outbreak. A number of these complaints were associated with issues different in nature and scope than those addressed in a 2006 Warning Letter sent to NECC. These complaints were related to the safety and potency of NECC and Ameridose products, issues that the FDA failed to routinely, if ever, inform the state about. Finally, FDA also considered — but never conducted — several additional inspections of the companies and related enforcement actions that, had they happened, may have averted the tragedy.
Energy and Commerce Committee Chairman Fred Upton (R-MI) and Oversight and Investigations Subcommittee Chairman Murphy (R-PA) stated, "We are saddened by the deaths of 53 people, and our heart goes out to the over 700 fathers, mothers, sons, daughters, husbands and wives now suffering from these contaminated drugs. Going into this investigation, we knew NECC and its sister company, Ameridose, were bad actors. But what makes this tragedy even more heartbreaking for these families is that this could have been prevented.
"After reviewing more than 27,000 documents, we found a dramatically different picture than the one painted by the FDA during our initial hearing in November. We now know that doctors, patients, providers, and whistleblowers tried to warn FDA for years that NECC and Ameridose were operating as manufacturers and marketing their products nationwide without patient prescriptions. The FDA was also warned about sterility and safety issues with the companies' products. Rather than do its job and protect the patients who were taking NECC and Ameridose drugs, FDA chose not to act. We found that FDA focused on perfecting their legal reasons for inaction instead of protecting families. Even the FDA staff wanted to go back and inspect these unsanitary manufacturers. And the FDA hierarchy said 'no.'
"We owe it to the families who lost loved ones and the 730 individuals still suffering to get answers from the FDA on why they failed to protect patients and how they will assure this never happens again," said Upton and Murphy.
At the committee's request, the FDA produced over 27,000 documents, which revealed the NECC and its sister company Ameridose had a long history with FDA. After a 2003 meeting, where FDA originally said NECC should be treated as a compounding pharmacy, a different picture of NECC began to emerge. The Massachusetts Board notified FDA that they had received emails from pharmacists in Wisconsin and Iowa suggesting that NECC was engaged in manufacturing. It was at this time that FDA also received a complaint from a drug company which prompted FDA to inspect NECC in September 2004. It took two years for the FDA to issue a Warning Letter. The NECC responded to the letter and denied all of FDA's allegations. It took FDA another two years to resolve the Warning Letter, as FDA did not respond to NECC until October 2008.
In the six years following the 2006 Warning Letter, FDA failed to take any enforcement action against NECC or Ameridose despite receiving complaint after complaint, often relating to the safety of the companies' drugs.
It is apparent from documents outlined in the supplemental report that FDA considered additional inspections and potential enforcement activities throughout this time period, but FDA delays in responding to past inspections, like the 2006 Warning letter, prevented FDA from acting.
For example, on January 14, 2006, Steven Silverman, then-Director of CDER's Division of New Drugs and Labeling Compliance (DNDLC), was forwarded an email from an individual in Texas detailing NECC's distribution of multiple-use vials of injectable methotrexate. On a subsequent but related exchange, he copied Samia Nasr, then-Team Leader of CDER's Compounding Team, and stated, "As we discussed, NECC is a repeat player, so it might deserve attention that other operations wouldn't merit. But the team is caught up with a range of high-profile issues, so this may need to wait (especially absent reported injury)."
On October 9, 2008, while discussions about inspecting NECC prior to issuing the response letter were ongoing, FDA's Los Angeles District Office received a complaint about a patient who reported an adverse reaction to an NECC product. In response to an FDA district compliance officer's recommendation to follow-up, FDA decided not to conduct any inspection because the 2006 Warning Letter was still pending. Four years after the underlying inspection, FDA finally sent a response letter warning NECC that a failure to correct the violations listed in the 2006 Warning Letter would result in enforcement action including seizure of the firm's products and/or an injunction against the firm.
After FDA responded to NECC, based on communications between FDA staff, there should have been no barrier to FDA conducting an inspection of NECC, especially in light of the additional issues and complaints that had been brought to the agency's attention while it worked on a response to NECC's January 2007 letter. In fact, with further evidence that NECC's practices were continuing to result in unsafe products, FDA finally seemed prepared to take decisive action. On February 11, 2009, after receiving some test results, a District compliance officer emailed a number of his colleagues, "CDER wants us to immediately (today) go [to] NECC to determine if the firm is willing to recall the Phosphatidyl choline [sic] injection it compounds. The drug is superpotent and not approved and should be recalled. We want to determine the batch size, and where distributed. The recall part should be done immediately and can be separate from the inspection."
However, FDA internal communications reveal they decided to continue to hold off. The documents do not explain the new delay, but FDA has confirmed no further inspection of NECC occurred until after the meningitis outbreak.
In May 2011, the FDA New England District compliance officer responsible for NECC spoke to an optometrist with the Veterans Administration who was inquiring about whether they could use NECC to repackage Avastin for them into single dose units. This communication is significant, because it once again confirms that FDA understood that NECC was acting more like a manufacturer than a traditional compounding pharmacy. In email correspondence, FDA admits that NECC's repackaging was "manufacturing and not compounding." During the November 2012 hearing, Commissioner Hamburg failed to mention that FDA knew that NECC was operating like a manufacturer and the agency had failed to pass along any information to the Massachusetts Board.
FDA's inaction with respect to NECC's sister company Ameridose may be even more egregious than in the case of NECC. Ameridose was different from NECC in one fundamental way: it had registered with FDA as a manufacturer and repackager of drug products. From 2009-2012, FDA failed to take action while complaints about Ameridose's products and practices mounted. Not only did FDA understand the nature and scope of Ameridose's practices, it was well aware of the dangers they were posing. Despite an increasing number of complaints, FDA decided to further delay action against Ameridose.
The meningitis outbreak would not have occurred if not for NECC's willingness to consistently cut corners and prioritize the expansion of their business over the safety of their products. However, contrary to previous FDA statements, NECC was not operating in the shadows. NECC was on FDA's radar since 2002. FDA had a deep understanding of the nature and scope of both NECC and Ameridose's operations.
View the entire report here.
View a comprehensive list of complaints from 2002-2012 against NECC and Ameridose here.