FDA Articles

After months of delay, the Senate confirmed Lester Crawford in July as the official head of the Food and Drug Administration. Crawford's nomination had been put on hold as various legislators sought to pressure FDA to take action on pet issues, such as drug importing and approval of an over-the-counter version of the "morning-after" pill Plan B. Senate Finance Committee chairman Charles Grassley (R-Iowa) reflected general concerns about the agency in criticizing Crawford for not tackling drug safety failures and FDA's "structural, personnel, cultural and scientific problems."

In the end, Grassley and most Senators agreed with the leadership on both sides of the aisle that FDA would be better off with a permanent chief than without. Now it's up to the new commissioner to demonstrate that FDA decisions will be based on scientific and medical evidence —and not on pressure from industry or political leaders.

Margaret O'K. Glavin became the director of FDA's Office of Regulatory Affairs (ORA) in May 2005 and now faces a serious challenge: finding ways to manage expanding oversight responsibilities in the US and abroad for ORA's regional and district inspection teams despite shrinking resources. Glavin recognizes that ORA cannot inspect all the facilities and operations under its purview and has to determine which ones are most vital to monitor more closely with increased frequency. This determination involves reorganizing the ORA staff, revising policies, and adopting risk-based approaches for "transforming" the field inspection process.

Jill Wechsler
The Food and Drug Administration recently unveiled its long-awaited Critical Path Opportunities List, which maps out a number of "scientific projects" for improving the testing and production of biotech therapies. In its March report, FDA recognizes that problems in the characterization, testing, and quality management of medical products can delay clinical trials and even completely block drug development.

At the same time, the White House officially nominated Acting Commissioner Andrew von Eschenbach to take over the top job permanently. Although von Eschenbach has provided strong support for the Critical Path initiative, his good efforts may not overcome the political issues blocking his confirmation as commissioner.

On March 16, 2004, the Food and Drug Administration (FDA) issued a position paper entitled: "Innovation or Stagnation...Challenge and Opportunity on the Critical Path to New Medical Products." The Critical Path Initiative (CPI), as it has come to be called, provided the FDA's analysis of the current drug development pipeline problem, characterized by a recent slowdown—instead of the expected acceleration—in innovative medical therapies reaching patients. The basic tenet of the FDA's analysis is that the applied sciences needed for medical product development have not kept pace with the tremendous advances in the basic sciences. Often, product development programs must be abandoned late into the development stage after extensive investment of time and resources.

For the past year, Margaret O'K. Glavin has been preparing for major changes at the US Food and Drug Administration's Office of Regulatory Affairs (ORA). Glavin became ORA director in May 2005, replacing John Taylor at a time when FDA's regional and district offices faced more responsibilities and shrinking funds. Meeting these demands will require "fundamental changes in the way we perform our work over the next 10 years," she said in a March 2006 memo. Glavin recognizes that ORA can't inspect all the facilities and operations under its purview and must decide which ones are most important to monitor more closely and more frequently. This prioritization involves reorganizing ORA staff, revising policies, and adopting risk-based approaches for modernizing the field inspection process.

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Clinical trials may take longer and become larger as proposals emerge to strengthen regulatory policies.
Members of Congress, patient advocates, and some industry experts say it is time to re-evaluate Food and Drug Administration approval and postapproval operations. Safety concerns about prescription drugs continue to mount, along with charges that new drugs are coming to market without adequate testing and that postmarket surveillance has suffered. Some legislators want to give FDA authority to require postapproval studies and labeling revisions. FDA officials maintain that recently proposed internal initiatives can fix most of its problems.

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Manufacturers, regulators, and public health officials are establishing new policies and expanding research initiatives to improve drug formulations and delivery systems. The US Food and Drug Administration recently approved many new products with novel delivery methods such as inhaled insulin and a depression drug transdermal patch. The agency also bolstered its staff with experts in pharmaceutical engineering and formulation to assess these challenging products.

The Critical Path Opportunities List unveiled by FDA officials in March cites "manufacturing novel dosage forms" as an area in which collaboration with industry and academia could remove roadblocks to new drug development. And, new drug formulations may eliminate complications related to managing temperature-sensitive drugs and vaccines through the distribution chain.

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New policies aim to simplify testing for single-pill combos and products that combine drugs with medical devices.
In January, the Food and Drug Administration made headlines by quickly approving a fixed-dose-combination (FDC) treatment for AIDS under a new policy that allows its use in developing nations. Pharma manu-facturers also are building commercial markets at home for FDCs that offer clinical benefit and/or reduced risk.

FDA is encouraging combo product development by modifying preclinical and clinical testing requirements, and clarifying manufacturing standards for new combinations of existing as well as new products. Pharma companies eye combination drugs as a way to both address multiple health needs and simplify treatment regimens. Health plans and insurers appear receptive to paying a premium for products that offer less risk and more convenience, but sponsors have to document long-term benefits in terms of savings and enhanced health.

It's the physician's job (to adapt a recent campaign phrase) to pick the right drug for the right patient at the right time. It's FDA's job to inform that decision. Clearly, as demonstrated by 2004's controversies over antidepressants and COX-2 inhibitors, the system is not working optimally.

The problem is rooted in the fundamental nature of the agency: Although FDA has significant expertise in overseeing drugs in development; it is not structured adequately for the demands of researching a drug after approval. The regulatory culture and tools used in drug development would be too cumbersome to use in the post-marketing environment. For instance, the gold standard of development, the double blind placebo-controlled trial, is impossible in the marketplace. A traditional regulatory approach cannot—in a reliable, prospective fashion—take into account the multitude of ways patients and healthcare systems use drugs.

The Food and Drug Administration's Prescription Drug User Fee program (PDUFA) has to be reauthorized by October 1, 2007, and all of the interested parties are fine-tuning their wish lists for "improvements." Although some consumer advocates and their Congressional allies blast user fees for extending industry control over the drug approval process, FDA officials, pharma companies, and patient disease groups applaud the program's success in ending "drug lag" and speeding new therapies to market.

FDA held a meeting in November to open the PDUFA 4 debate. The added resources from user fees over the last decade have improved the NDA approval process, observed Steven Galson, director of the Center for Drug Evaluation and Research (CDER). Most new drug applications (NDAs) need only one review cycle to gain approval, he pointed out, and the scientific expertise of CDER's staff has improved noticeably.