FDA Risked Its Integrity During Heparin Probe

In a scathing report, the US General Accountability Office harshly criticizes the FDA for its handling of the 2008 heparin crisis. Specifically, the GAO says the FDA gave the appearance of favoring Momenta Pharmaceuticals by retaining the drugmaker to provide free consulting at the same time Momenta was seeking approval to sell a generic version of the Lovenox bloodthinner, which is derived from heparin.

By accepting consulting help from Momenta - in particular, co-founder Ram Sasisekharan and morethan two dozen staffers from the drugmakers - "agency officials ran the risk of undermining public confidence in the integrity of FDA’s operations..." The GAO also noted the agency left itself open to future claims for payments for services from the drugmaker (you can read the 63-page report here). The story was first reported by The Wall Street Journal.

The upbraiding comes two years after Amphastar Pharmaceuticals - a Momenta rival that is still awaiting FDA approval for its own generic Lovenox - paid more than $100,000 to the Kroll private eye firm to investigate Janet Woodcock, who heads the FDA’s Center for Drug Evaluation and Research. Why? Amphastar worried the FDA was delaying approval, favoring Momenta (see this) and alleged Woodcock’s research work with Momenta, including a scientific paper that was published, created the appearance of a conflict. The FDA later ruled none existed (look here).

The GAO findings, however, now appear to support the Amphastar allegations that its rival was receiving partial treatment. "Everyone closely involved saw that it was stacked and the whole direction was toward Momenta," Richard Adams, a former official in the FDA's generic-drug division who retired this year, tells the paper. More recently, Amphastar has sued the FDA in hopes of halting sales of Momenta's generic Lovenox, but to no avail (back story).

For its part, FDA officials told the GAO that "they believed that there was insufficient time to address these ties in the midst of the heparin crisis and that the CDER staff, who identified these scientists (five scientists Momenta and elsewhere), were confident that they could independently assess the input from these scientists through robust, detailed, and transparent discussions."

Here is what the GAO has to say...

"In February 2008, FDA officials contacted five external scientists, including one who was employed by the agency as a special consultant, for assistance with the heparin crisis, and FDA worked with these scientists for varying time periods. Agency officials told us that they sought the advice of these external scientists because the agency lacked the necessary instrumentation and expertise to identify and develop new testing methods to detect the specific contaminant.

"One of the scientists was a cofounder and member of the board of directors, as well as an equity interest holder, in a third firm, which, at the time of the crisis, had a pending application for a heparin product before FDA. The agency allowed this scientist to obtain assistance in conducting analytical work to identify the contaminant in heparin from this firm despite its pending application for a heparin product. This drug manufacturer dedicated approximately 30 staff members from its analytical and biology groups for periods ranging from a few weeks to three months to assist in the effort to identify the contaminant in heparin...

"FDA officials were aware of the scientists’ ties to heparin manufacturers, but did not take adequate steps to consider whether these relationships exposed the agency to the risks described in its guidance or to address these risks before engaging them. FDA officials told us that they believed that there was insufficient time to address these ties in the midst of the heparin crisis and that the CDER staff who identified these scientists were confident that they could independently assess the input from these scientists through robust, detailed, and transparent discussions; they said that this would address any appearance problems related to the scientists’ input...According to FDA, the agency’s main concern about engaging these experts was that their relationship with the pharmaceutical firms might limit their ability to participate in a free exchange of information with the agency."

The GAO goes on to chastise the FDA for failing to consider "whether the agency’s acceptance of voluntary services from a scientist with an interest in a firm with an application pending before FDA, along with employees of that firm, would compromise, or appear to compromise, the agency’s activities, including its activities related to the approval of heparin products. Moreover, FDA did not fully disclose the existence or extent of these scientists’ interests while they were providing assistance or afterwards. CDER staff did not consult with the Office of Chief Counsel or agency ethics officials about their working arrangements with these two scientists or seek advice as to whether the arrangements were consistent with the agency’s ethics standards.

"...FDA’s acceptance of voluntary services in connection with the heparin crisis also exposed the agency to the risk of claims for payment for the services provided.

"FDA officials told us that the agency was authorized to accept voluntary services during the heparin crisis under an emergency exception and, therefore, was not required to obtain a written agreement that the services were offered with no expectation of payment. The statute provides an exception for emergencies involving the safety of human life or the protection of property, which the statute defines as circumstances involving an imminent threat to the safety of human life or the protection of property...The acceptance of services under the emergency exception would give rise to obligations - that is, financial liabilities - for which claims for payment could be made," the GAO concludes.