Coming meetings of expert panels that advise the Food and Drug Administration will shed light on a key question: Are the FDA and its outside committees raising the bar on approving new drugs amid public controversies over the safety of some widely used medicines?

In the first two weeks of September, FDA advisory committees will review a series of potential blockbuster drugs, including an inhaled insulin called Exubera, to be marketed by Pfizer Inc.; Bristol-Myers Squibb Co.'s Pargluva for adult-onset diabetes; and another Bristol-Myers medicine, Orencia, aimed at treating rheumatoid arthritis. Analysts predict each drug could have annual sales of more than $1 billion if they pass the FDA approval process.

The industry will view the votes as a signal of how deeply a sense of caution on drug approvals has taken hold, particularly in the wake of last week's $253 million court verdict against Merck & Co. over its painkiller Vioxx, which was voluntarily pulled from the market because of concerns about its safety.

"This is really a critical period," said Tom Garvey, a former FDA official who now consults for the drug industry. "It will be very important to see where they set that balance point between benefit and risk."

The agency generally, though not always, follows the advice of the advisory committees, which are composed of outside academic experts charged with evaluating specific drugs or issues. The committees have come in for their own tough scrutiny amid concern about some panel members' ties to the drug industry.

Scott Gottlieb, a deputy FDA commissioner, said the agency's review process hasn't changed. But, he added, he is concerned that criticism aimed at advisory-committee members could "have a chilling effect on their ability to have a frank and open scientific discussion," though this hasn't happened yet.

The meetings of three different committees come as drug companies and the FDA are focusing more on the side effects of drugs. The FDA, which says approval rates haven't slowed, is placing a heavy emphasis on finding and quickly disclosing problems with medicines in the wake of scrutiny from Congress. The industry has followed suit, a trend likely to be accelerated by the Vioxx verdict, which pivoted on jurors' perception that Merck had failed to fully inform patients about risks.

The highest-profile drug that will face a committee vote next month is Exubera, the subject of a Sept. 8 meeting. A joint venture of Pfizer, Nektar Therapeutics and Sanofi-Aventis SA, the drug would be the first inhalable form of insulin -- a breakthrough that would mark a significant change in how diabetics medicate themselves. The drug would provide an alternative to injections.

Exubera is no better at managing blood sugar than is conventional insulin, though, so the main reasons to offer the drug boil down to patient preference. The drug's backers are likely to argue that is a significant benefit, since a large proportion of diabetics are currently unable to achieve adequate control of their blood sugar.

But Exubera comes with a potential safety worry. Patients using the drug experience a tiny deterioration in their breathing capacity -- from 1 percent to 1.5 percent -- compared with those using other diabetes drugs, according to Pfizer studies. Concerns about lung damage delayed Exubera's application to the FDA for three years while the companies conducted additional tests.

Pfizer believes it will be able to show the committee that the declines didn't worsen with time and that they are reversible, disappearing in less than three months after patients stopped Exubera. Pfizer said recent company studies showed that adult-onset, or type 2, diabetics who added Exubera to their treatment of oral diabetes drugs achieved adequate control of their blood sugar for two years, without declines in lung function that the researchers described as clinically important. Pfizer said it is confident its data will help persuade the FDA panel that the drug is worthwhile.

Diabetes specialists are watching the drug closely. Martin Abrahamson, acting chief medical officer at the Joslin Diabetes Center in Boston, said the lung-function issue appears "clinically insignificant." Several quality-of-life surveys indicate "a high degree of acceptance" for inhaled insulin among patients, said Dr. Abrahamson, but it remains to be seen "how that translates into the real world." Dr. Abrahamson has received some research funding from Pfizer but wasn't involved in trials of Exubera.

On Sept. 9, the same committee will examine another potentially important new diabetes treatment -- Bristol-Myers's Pargluva -- which would be marketed with Merck and aimed at patients with type 2 diabetes. Bristol-Myers is likely to argue that the drug is an important new product because it both helps control patients' blood sugar and brings down triglycerides, or fats in the blood, while current drugs target just the blood sugar. Studies on Pargluva that have been made public also showed a reduction in LDL, or "bad" cholesterol, and an increase in HDL, or "good" cholesterol, levels.

But the FDA will likely bring up evidence that the drug may be linked to side effects, including fluid retention, which may lead to congestive heart failure, especially at higher doses. The effects on triglycerides and cholesterol "look potentially exciting, but I'm not sure the benefits outweigh the risk," said Carol J. Levy, an endocrinologist at New York Weill Cornell Medical Center. "At a dosage without side effects, will it get you where you want to be?"

Bristol-Myers is facing another important committee meeting Sept. 6, for Orencia, a drug it developed to treat rheumatoid arthritis. Although the drug so far isn't seen as having a major safety question, it will come before the committee that handled the class of painkillers that includes Vioxx and has been at the center of the debate over the risks of medicines.

The following week, the FDA's cancer-drug committee will highlight a different issue: how the FDA and its advisers are weighing evidence under the agency's accelerated-approval process, which requires less proof in exchange for follow-up research after the drug goes on the market. In May, the committee turned down Johnson & Johnson's leukemia drug Zarnestra, or tipifarnib, for accelerated approval. Some members raised broader questions about how the accelerated process works.

The committee will examine Celgene Corp.'s Revlimid, among others, as a candidate for accelerated approval. Revlimid is being reviewed for anemic patients with a type of blood cancer and a particular genetic abnormality who require regular blood transfusions.