Regulatory Beat: Changes and Challenges at FDA

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BioPharm International, BioPharm International-11-01-2005, Volume 18, Issue 11

Facts@FDA...ultimately will contain current product labeling information plus safety data gleaned from adverse event reports.

After months of turmoil over drug safety, vaccine shortages, and pressure to import low-cost drugs from abroad, FDA faces further upheaval from within. Commissioner Lester Crawford resigned abruptly in September after only two months in the top spot. The White House named Andrew von Eschenbach, director of the National Cancer Institute (NCI) at the National Institutes of Health (NIH), as acting FDA commissioner. But his initial decision to remain NCI director while taking the helm of FDA raised an outcry. Von Eschenbach agreed to drop day-to-day management of NCI in the face of clear conflicts of interest between advocating for speedy access to new cancer treatments while overseeing the assessment of the safety and effectiveness of those therapies.

Jill Wechsler

Von Eschenbach reassured FDA staffers that he would work hard to ensure a "smooth transition" and to keep agency efforts "on track." FDA leaders insist they will carry on as usual during the transition to new leadership. Following Crawford's terse resignation announcement, Deputy Commissioners Scott Gottlieb, Janet Woodcock, Murray Lumpkin, and Patrick Ronan sent a message to all FDA employees emphasizing their commitment to the agency and intention of continuing its important work. Von Eschenbach is familiar with the FDA drug testing and review process from collaborative NCI-FDA efforts. He has been enthusiastic about joint initiatives to validate biomarkers and advance personalized medicine.

Von Eschenbach also is highly regarded in the cancer research field, knows his way around Capitol Hill, and has personal connections to the Bush family from his leadership position at Houston's M.D. Anderson Cancer Center. Cancer patient groups have praised his support for accelerating access to new treatments, and biotech companies publicly applauded the choice. James Greenwood, president of the Biotechnology Industry Organization, described the acting commissioner as someone with "unique insights into the critical need to advance new treatments for patients with life-threatening illnesses."



However, von Eschenbach officially remains director of NCI, a position he wants to retain because HHS secretary Mike Leavitt has indicated that the acting commissioner will not be named to take the reins at FDA permanently. Von Eschenbach's enthusiasm for approving new drugs quickly has drawn fire from parties that are equally concerned about protecting relatively healthy patients from high-risk medicines. In addition, the acting commissioner knows little about the many complex and critical regulatory programs that FDA oversees, such as concerns about the safety and testing of implantable medical devices. FDA staffers already are finding it difficult to move forward with controversial initiatives. A much-anticipated white paper on follow-on biologics, for example, won't be released any time soon, apparently to give the lawyers time to further examine policy and legal issues.

At FDA, von Eschenbach has to deal with many of the issues that plagued Crawford and delayed his confirmation by the Senate last spring. FDA still faces proposals from Congress to overhaul its oversight of drug safety arising from the Vioxx debacle, to ensure adequate supplies of vaccines for influenza and childhood diseases, and to permit broader access to the morning-after pill, Plan B. Although Congressional leaders, manufacturers, and the bioresearch community have urged the White House to name a qualified individual for that spot as soon as possible to head FDA permanently, the cloud hanging over Crawford's departure won't make it easy to attract a talented scientist and administrator to the job. Senate Democrats refuse to consider candidates with ties to the pharmaceutical industry, and conservative Republicans want someone who shares their political views. Current FDA officials face difficulties because of close ties to recent agency missteps. Further complicating the picture is an investigation into the reasons for Crawford's surprise resignation; Senate leaders who backed Crawford's appointment want to know whether they were denied access to important information during the confirmation process. FDA desperately needs a strong leader who can restore public trust in the troubled agency – but this may be hard to find.


An immediate challenge for FDA's leadership is to reassure its constituents that drug safety problems are not creating a go-slow approach in FDA review offices. Some observers believe that safety concerns are delaying the approval of important new therapies, and that advisory committee meetings spend more time than is warranted discussing minor adverse events. FDA recently postponed approval of Celgene's blood disorder treatment, Revlimid (lenalidomide), pending further review of the company's risk-management plan for preventing pregnant women from using this newer version of thalidomide.

The importance of addressing drug safety issues is apparent from a number of agency initiatives. FDA has scheduled a public meeting next month (December 7-8) to solicit public comment on its traditional means of communicating about drug risk, such as issuing talk papers, health advisories, press releases, and posting adverse event information from its MedWatch system. The agency's new Drug Safety Oversight Board has begun to privately assess safety concerns, while agency staffers evaluate comments on the proposal to make public emerging drug safety information on a new "Drug Watch" website.

These and other activities are part of a broad initiative to build a central electronic information system that can provide up-to-date information on medical product safety and appropriate use. Unofficially dubbed "Facts@FDA," the system ultimately will contain current product labeling information plus safety data gleaned from adverse event reports. Additional information on drug safety and outcomes also will come from Medicare and health plan information systems that collect extensive data on prescription drug prescribing and use; FDA signed a contract in September with four leading health plans to provide post-market surveillance data on 11 million covered patients.

A key component of Facts@FDA will be the DailyMed data bank of prescription drug labels, operated by the National Library of Medicine. Manufacturers began submitting changes to drug labels electronically this month (November 1, 2005) using the recently adopted Structured Product Labeling (SPL) standard. DailyMed also will obtain electronic drug labels as new drugs are approved and as manufacturers submit annual reports with revised labels to fit the new format.

Over the next year, DailyMed should obtain electronic information on all marketed prescription drugs, including generics and biotech therapies regulated by the Center for Drug Evaluation and Research (CDER). The system will make it easier to revise label information to fit the new format established by FDA's final professional labeling rule, which has been anticipated for many months. Ultimately, patients will be able to obtain current product labeling information via the Internet or from pharmacy kiosks, eliminating the outdated paper package inserts that are costly for manufacturers to produce and of little value to patients.

The future vision is for DailyMed label information to link to adverse event reports filed by manufacturers and FDA's MedWatch program. FDA currently makes this data available to the public on a quarterly basis, but Gottlieb suggests that more frequent Internet postings may be useful. FDA's hope is that making it easier for healthcare practitioners to access current drug adverse event information may encourage more physicians to report signs of trouble to MedWatch, something they now do very infrequently.

A third component of the envisioned Facts@FDA system may be reports of emerging drug safety signals from FDA's proposed DrugWatch website. Pharma companies and health experts worry that the public may become confused and overly alarmed by reports of drug safety problems that may be very preliminary — but appear as official FDA warnings. Whatever form the final system takes, more immediate access to information on a drug's side effects and appropriate use could address many post-approval drug safety concerns and affect how safety and efficacy information is collected in clinical trials.

Jill Wechsler is BioPharma International's Washington editor, 7715 Rocton Avenue, Chevy Chase, MD 20815, 301.656.4634,