Pink Sheet is part of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC’s registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.

This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, please call +44 (0) 20 3377 3183

Printed By



Executive Summary

House Energy & Commerce/Health Subcommittee Chairman Waxman (D-Calif.) is looking into the shaping of the FDA drug approval process reforms announced jointly by Vice President Quayle's Council on Competitiveness and the agency as a prelude to possible hearings next year. One of the lines of inquiry involves the extent of possible influence on the council by the pharmaceutical industry. For example, in a letter to the council, Waxman pointed out several ties between the White House and Lilly. President Bush is a former member of Lilly's board of directors; Vice President Quayle often represented his constituent company in negotiations as a senator from Indiana; and Lilly Corporate Affairs Division VP Mitchell Daniels was a political director in the Reagan White House. The council is understood to have asked Lilly for technical advice in drawing up a number of its proposals. If Waxman holds a hearing focusing on industry influence on the proposals to streamline the FDA approval process, he can choose from a host of potential industry witnesses that made presentations before the council. The Pharmaceutical Manufacturers Association, the Industrial Biotechnology Association and the Association of Biotechnology Companies presented their views to the council. In addition, the council heard presentations from various groups such as the FDA Council, the American Medical Association, the American College of Pediatrics, the Cystic Fibrosis Foundation, the American Cancer Society and the Alliance for Aging Research. Waxman is one of several members of Congress who are examining the council's role in reviewing FDA regulation. Waxman, Rep. Dingell (D-Mich.) and Sen. Kennedy (D-Mass.) jointly signed a Nov. 13 letter asking FDA Commissioner Kessler not to implement any council recommendations until they have been reviewed by Congress, and all three legislators are said to be interested in holding hearings on the proposals. Rep. Weiss (D-N.Y.) issued a subpoena for documents recording correspondence between the council and FDA ("The Pink Sheet" Nov. 18, p. 9). FDA supplied the documents on Nov. 21, and they are under review by Weiss staffers. Because the agency supplied the requested documents, Weiss canceled a hearing that had been scheduled for Nov. 22 before his House Government Operations/Human Resources and Intergovernmental Relations Subcommittee. In addition, the Senate Governmental Affairs Committee chaired by Sen. Glenn (D-Ohio) is investigating the Competitiveness Council's role in reviewing FDA regulations. One committee member, Sen. Levin (D-Mich.), has complained that Congress has no means to determine the council's influence on FDA's rulemaking process ("The Pink Sheet" Sept. 30, T&G-10). Levin is particularly interested in how draft nutritional labeling proposals were changed by the council before being published. Predicted resistance to the proposals by FDA career employees has surfaced. In a Nov. 20 letter to Vice President Quayle, FDA Oncology and Pulmonary Drugs Division Medical Reviewer Grant Williams, MD, maintained that independent reviews of Phase I INDs by Institutional Review Boards would endanger study subjects. "It is my duty to inform you of what I perceive to be a real danger to the lives of patients receiving investigational cancer drugs," Williams wrote. The council's recommendation that FDA allow local IRBs to review and approve IND requests to conduct Phase I trials was one of 11 reforms targeted at improving the drug approval process ("The Pink Sheet" Nov. 18, p. 7). Williams maintained that over the past two years of reviewing NDAs in the division, he has "noted numerous dangers in applications that were not foreseen by investigators or [IRBs]." Williams said it is "unbelievable" what IRBs can overlook. "The full ramifications of data involving chemistry, animal toxicity, pharmacokinetics and mechanistic factors" cannot be appreciated by reviewers who are not exposed to such situations frequently, Williams argued, adding that "such exposure is unlikely to occur at the typical IRB." Williams contended that "some patients would likely have died from unforeseen drug toxicity" without intervention from FDA reviewers who are trained in pharmacokinetics. Such a situation allegedly occurred with Fujisawa's anti- transplant rejection drug FK-506. The local IRB had cleared University of Rochester Phase I studies to start with a high dose of FK-506. However, the dose was lowered after FDA Pulmonary and Oncology Division Director Gregory Burke, MD, intervened. Williams said the drug was associated with renal toxicity that was not observed at the beginning of the trials. The medical reviewer further suggested that "changes at the IND stage are unlikely to speed the development of drugs unless investigators resort to unethical practices." He pointed out that the division currently does not put INDs on clinical hold unless the submission "appears very dangerous or is obvious quackery." Routine problems generally are resolved "quickly" by telecopy or telephone without instituting a clinical hold, he said. Williams pointed out that FDA Center for Drug Evaluation & Research Director Carl Peck, MD, is encouraging faster Phase I development of cancer drugs by using pharmacokinetic data in early trials. The strategy, which also allows improved individualized dosing, will be lost if IRBs review Phase I trials independent of FDA, Williams said. "Other negative effects" that may result from the proposal include "investigational quackery," which Williams said "will increase exponentially in the cancer area." IND data not reviewed by FDA "will be used to attract patients to exotic centers for the newest potion," he maintained. "Enough of this goes on now even with the existing structure," he acknowledged. "At later stages of drug development, we will be faced with Phase I or Phase II data from human trials which may be of questionable quality." Williams recommended limiting FDA authority to place studies on clinical hold as an alternative strategy to speeding Phase I development. "It would be more constructive to continue the requirements for IND registration with the agency, and only curtail agency authority to put the study on clinical hold in these particular circumstances." Such an alternative would reflect FDA regulation of "new protocols submitted under an improved IND," Williams noted. "For new protocols agency registration is required, [but] prospective approval is not," he explained. "However, the agency has the opportunity to review and comment on the design and safety of such protocols after their submission."

You may also be interested in...

Part D Discount Liability Coming Into Focus: CMS Releases Drug Cost Data

Newly released Medicare Part D data sheds light on the sales hit that branded pharmaceutical manufacturers will face when the coverage gap discount program gets under way in 2011

FDA Skin Infections Guidance Spurs Debate On Endpoint Relevance

FDA appears headed for a showdown with clinicians and the pharmaceutical industry over the proposed new clinical trial endpoints for acute bacterial skin and skin structure infections, the guidance's approach for justifying a non-inferiority margin and proposed changes in the types of patients that should be enrolled in trials

Shire Hopes To Sow Future Deals With $50M Venture Fund

Specialty drug maker Shire has quietly begun scouting deals with a brand-new $50 million venture fund, the latest of several in-house investment arms to launch with their parent company's pipelines, not profits, as the measure of their worth




Ask The Analyst

Ask the Analyst is free for subscribers.  Submit your question and one of our analysts will be in touch.

Your question has been successfully sent to the email address below and we will get back as soon as possible. my@email.address.

All fields are required.

Please make sure all fields are completed.

Please make sure you have filled out all fields

Please make sure you have filled out all fields

Please enter a valid e-mail address

Please enter a valid Phone Number

Ask your question to our analysts