Heparin Crisis Spurs Changes In FDA Emergency Response Policies
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Internal and external evaluations of FDA’s handling of the heparin contamination crisis two years ago have led to changes in the agency’s emergency response strategy and a new policy on emergency collaborations with outside experts. The new Emergency Operations Plan (EOP), finalized in September, is aimed at addressing difficulties encountered during the heparin crisis, including a lack of specificity on leadership and coordination of the response in the previous Emergency Response Plan (ERP). The agency also instituted a new policy in October requiring FDA staff to consider and protect against risks posed by collaborations with outside experts in emergency situations. The two documents are discussed in a Government Accountability Office review, released Nov. 9, of FDA’s response to the adulterated heparin products that manifested in hundreds of adverse event reports in 2008. The report was requested by House Energy and Commerce Committee Ranking Member Joe Barton (R-Texas), who is making a bid for the chairmanship slot following the Republican party’s takeover of the House in the Nov. 2 elections GAO's final report reviews various elements of FDA’s response, including its efforts to avoid a domestic heparin shortage amidst a recall of contaminated products and increased inspectional oversight of Chinese firms involved in heparin production. The report also reflects how FDA has adapted its emergency response procedures as a result of the heparin incident. “Lessons Learned” Review The report recaps the agency’s internal evaluation of lessons learned in responding to the crisis. FDA’s heparin response actions were coordinated under the ERP in place since 2005. Although the Office of Crisis Management (OCM) initially coordinated the response across numerous FDA centers and offices, the Center for Drug Evaluation and Research took over the role of lead coordinator once it was determined that the adverse events were related to the heparin drug product. OCM participated in heparin task force meetings convened by CDER but had no role in the ongoing coordination of response efforts. Documents from “lessons learned” meetings held after the crisis show that a lack of detail in the ERP and absence of agency-level coordination may have caused process delays and difficulties with internal and external communication, GAO says. Since the ERP did not specify who should coordinate the agency’s response, it was unclear whether OCM or CDER should assume this role. When leadership transitioned from OCM to CDER, center officials spent time determining roles. In addition, Center for Devices and Radiological Health officials said issues related to heparin-containing medical devices were often not addressed in CDER’s communications.
FDA began developing a new emergency response plan, the EOP, in October 2008. This now-finalized plan, which replaces the ERP, contains a section on coordination at the agency level within FDA’s headquarters and offers guidance and a coordination structure that can be used during an incident. The plan calls for the designation of an Agency Incident Coordinator to manage an event at the agency level and serve as a communications bridge between the commissioner’s office and the agency’s centers and offices. An Agency Executive Group, comprising senior FDA officials, will be convened to provide strategic policy direction and guidance for major response activities. Collaborations With External Scientists While FDA acted on its own initiative to rework its emergency response strategy, its new policy on consulting outside experts was developed in response to GAO’s criticisms (Also see "Heparin Crisis Leads To New FDA Policy On Consulting Outside Experts" - Pink Sheet, 9 Nov, 2010.). FDA engaged five external scientists during the crisis to assist in identifying and developing tests to detect the heparin raw ingredient contaminant, oversulfated chondroitin sulfate. Two of these individuals had professional and financial ties to firms associated with contaminated heparin, and one of the two was a co-founder, board member and equity interest holder in a third company that had a heparin product application pending at FDA. Although GAO does not identify any of the firms or individuals by name, it is clear that the latter company is Momenta Pharmaceuticals. In 2008, CDER Director Janet Woodcock and other agency staff co-authored two scientific journal articles on heparin contamination with several scientists from Momenta, including company co-founder and board member Ram Sasisekharan and co-founder and chief scientific officer Ganesh Venkataraman. At the same time that Momenta scientists were helping FDA, the company and its partner Sandoz were seeking approval of a generic version of Sanofi-Aventis’ low molecular weight heparin Lovenox. FDA approved the ANDA in July 2010, making it the first generic enoxaparin approved (Also see "FDA Approves Momenta/Sandoz' Lovenox Generic Without Need For Clinical Studies" - Pink Sheet, 26 Jul, 2010.). Amphastar Pharmaceuticals alleged Woodcock’s ties to Momenta resulted in extra immunogenicity testing requirements being placed on its own enoxaparin ANDA, delaying approval. Amphastar sought Woodcock’s recusal from review and approval of generic enoxaparin. FDA said the HHS Inspector General’s office cleared Woodcock of any wrongdoing. Nevertheless, in August 2009 she decided not to involve herself in future decisions involving generic enoxaparin. In October, Amphastar sued FDA over its detention of heparin raw ingredient shipments from the firm’s Chinese subsidiary (Also see "Amphastar Lawsuit Over Heparin Shipments Suggests Lovenox ANDA Approval May Be Far Off" - Pink Sheet, 1 Nov, 2010.).
FDA officials failed to assess whether the scientists’ ties to firms associated with contaminated heparin, or with a sponsor that had a pending application, would compromise the agency’s integrity or undermine public confidence, GAO says. The report also criticizes FDA officials’ failure to protect against potential claims seeking payment for the services provided by these outside scientists. In its draft report, GAO recommended FDA develop a formal process for evaluating risks of collaborations with outside entities. FDA addressed this recommendation through a Staff Manual Guide, “External Expert Gratuitous Services In An Emergency,” that went into effect in mid-October. The policy requires outside experts to agree in writing that they will not receive compensation and will waive any future claims against the government. They also must provide financial disclosures and submit to conflict-of-interest screening. By Sue Sutter |