March 13,2008

Grassley says changes to improve FDA post-market review remain elusive

WASHINGTON -- Senator Chuck Grassley is asking Food and Drug Administrationofficials to explain how a new agency initiative to improve its oversight of drugs approved forthe market place is more than cosmetic.

Grassley said he’s concerned that the “Safety First” initiative launched in February maynot get at the problem with post-market surveillance by the FDA. “The office in charge ofapproving drugs in the first place is allowed to have power over the office that specializes in what happens with drugs after they’ve been on the market for awhile,” he said. “This structurecreates a conflict where the pride that goes with having approved a drug can get in the way of anobjective review of whether a drug is turning out to be as safe and effective as it ought to be, andthere’s no evidence that this structure has changed with the ‘Safety First’ initiative.”

Since 2004, Grassley has conducted active oversight of the FDA’s post-marketsurveillance of drugs, biologics, medical devices and veterinary medicines. He has repeatedlyshown that serious adverse events that emerge after a drug is on the market do not necessarilyget prompt attention from the Office of New Drugs. He has also revealed that safety concernsraised by the Office of Surveillance and Epidemiology were sometimes ignored by the Office ofNew Drugs, which is responsible for determining any regulatory actions taken to address apost-marketing drug safety issue.

Legislation introduced by Grassley in 2005 and 2007 would have set up a new andindependent center within the FDA called the Center for Postmarket Evaluation and Research forDrugs and Biologics which would have been responsible for monitoring the safety of drugs andbiologics once they are on the market in consultation with other existing Centers at the FDA, andwould have had the authority to take corrective action if a drug or biologic presented a risk topatients. Congressional leaders did not incorporate Grassley’s initiative in the broad-based,10-year reauthorization legislation for the FDA that was enacted in 2007.

The prestigious Institute of Medicine and the independent Government AccountabilityOffice issued separate reports in 2006 identifying major shortcomings with the FDA’spost-market surveillance of drugs.

Grassley asked the FDA Commissioner for a staff-level briefing on the “Safety First”initiative in a letter sent today. The text of that letter, which spells out Grassley’s concerns aboutthe initiative, follows here.

March 13, 2008

The Honorable Andrew C. von Eschenbach, M.D.
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Commissioner von Eschenbach:

The United States Senate Committee on Finance (Committee) has jurisdiction over theMedicare and Medicaid programs and, accordingly, a responsibility to the more than 80 millionAmericans who receive health care coverage under those programs to oversee the properadministration of the programs, including the payment for prescription drugs regulated by theFood and Drug Administration (FDA or Agency). As Ranking Member of the Committee, Ihave the duty to ensure that FDA upholds its responsibility to the public’s health by properlyregulating the nation’s drug supply and ensuring that the drugs Americans use are safe andeffective.

Recently, the FDA announced its “Safety First” Initiative, an effort within the Center forDrug Evaluation and Research (CDER) to “strengthen and modernize” FDA’s oversight of drugson the market. In an email to all CDER staff, Acting Center Director Janet Woodcock outlinedsome of the steps that will be taken to implement this initiative, including establishing thepositions of Deputy Director for Safety and Safety Regulatory Project Manager within the Officeof New Drugs (OND) and laying out the respective responsibilities of OND and the Office ofSurveillance and Epidemiology (OSE) in addressing drug safety issues.

Over the last four years I have investigated and questioned how the FDA handlespost-market surveillance of drugs, biologics, medical devices, and veterinary medicines to assesswhether or not the Agency is fulfilling its primary mission to protect public health. In particular,my investigations have shown repeatedly that serious adverse events that emerge after a drug ison the market do not necessarily get prompt attention from the Office of New Drugs (OND).Further, safety concerns raised by the Office of Surveillance and Epidemiology (OSE) weresometimes ignored by OND, which is responsible for determining what, if any, regulatoryactions will be taken to address a post-marketing drug safety issue.

I have frequently pointed out that this imbalance between the office responsible formonitoring post-marketing drug safety and the office that puts drugs on the market in the firstplace has resulted in delayed action and even inaction on serious post-marketing safety concerns.As you are aware, the Institute of Medicine also identified thisimbalance in authority between OND and OSE as a major weakness in the drug safety systemand recommended joint authority in the post-approval setting.

Congress didn’t take the opportunity to address this fundamental problem, and it appearsthat FDA’s response to the call for strengthening and better defining OSE’s role may be merelycosmetic. Dr. Woodcock claims in her email to CDER staff that “OSE will be playing anexpanded role in the resolution of certain drug-related safety issues and assuming lead regulatoryresponsibility for areas related to observational epidemiologic studies and medication errorprevention.” As I understand it, however, these regulatory responsibilities have always been inOSE’s domain; so there's nothing new there. The memorandum of agreement to be establishedunder the Safety First Initiative will only be making these responsibilities explicit. In addition,according to The Wall Street Journal, an FDA official stated that, “I think we really believethat…the team that has been in charge of drug development, that knows the drug best of all,really needs to be in charge.”[1]

Accordingly, I request that the FDA provide a briefing for my Committee staff to discussthe Agency’s Safety First Initiative. I would appreciate FDA elaborating on the details of theinitiative and the timeframes for implementation. In particular, please explain FDA’s decision tomaintain what appears to be the status quo—OSE continuing to play the role of consultant toOND on post-marketing safety matters. In addition, I would appreciate a discussion of thespecific responsibilities of the new positions to be created within OND and what their roles andresponsibilities will be vis-à-vis OSE.

The Wall Street Journal also reported that the FDA is creating a new appeals process sothat scientific disagreements between offices can be appealed to higher-level officials, up to theOffice of the Commissioner. Please have your staff prepared to describe FDA’s plans for thenew appeals process and how it would improve on the current ad hoc system for resolvingdisputes.

I look forward to hearing more about the Safety First Initiative and request that thebriefing be scheduled by no later than March 26, 2008. Thank you for your cooperation.


Charles E. Grassley
United States Senator
Ranking Member of the Committee on Finance