Pharmaceutical companies see U.S. regulators applying a tougher standard to some new medicines by looking for evidence they are better than drugs already on the market, officials told Reuters this week.

The Food and Drug Administration is demanding more safety data amid a heightened spotlight on risks, after the recall of Merck & Co's pain drug Vioxx in 2004, executives said.

Some said FDA reviewers have shifted their mindset and now look at how an experimental drug compares with what is already on the market. The law says medicines must be proven safe and effective. Usually they are compared to a placebo in pre-market trials.

I strongly believe that regulators increasingly look not only at the element of safety and efficacy, (but also) does it bring more to what is out there already, Roche Holding AG CEO Franz Humer said at the Reuters Health Summit in New York.

Humer said that scenario was good for Roche, which has focused on products that are clearly different than others.

AstraZeneca Plc Chief Executive David Brennan said the FDA was seeking more data than in the past and asking questions about alternative therapies. Products that are not first in class ... are looked at differently than the pioneer drugs, he said.

Deputy FDA Commissioner Janet Woodcock said the agency has placed more emphasis on safety amid broader scrutiny of FDA decisions by the public, lawmakers and interest groups.

But she said the agency has always looked at comparable drugs' safety records when reviewing new medicines.

We have always turned down drugs that have major liabilities compared to standard of care, said Woodcock, who has worked for the agency since 1986.

The FDA has no standard you have to prove yourself better than existing therapy on efficacy, Woodcock said. The standard has not changed.

For example, if a drugmaker brought the agency a drug in a class full of alternatives, and it caused bloody diarrhea when others did not, the FDA is likely going to pass, she said.

Maybe (the idea) is being articulated more clearly in the current environment, she said.

Through October, the FDA approved 15 novel drugs this year. The total for 2006 was 22. Recent years have lagged far behind the 53 cleared in 1996 during a mid-1990s boom for drugmakers.

FDA data show manufacturers have submitted fewer new drug applications in recent years than in the past. About three-quarters of them eventually get approved, and that rate has remained steady, Woodcock said.

Even so, complaints about FDA caution have been lodged for years by various drugmakers, some of which may not like agency rejections or want their products cleared more quickly.


Many executives who spoke to Reuters said Vioxx marked a turning point toward extra scrutiny of side effects. The arthritis drug was linked to heart attacks and strokes, and critics said the FDA should have paid more attention to early signs of problems.

The post-Vioxx environment clearly has made people more risk averse. I'm a little surprised by the prolonged risk-averse climate, Schering-Plough Corp (SGP.N: Quote, Profile, Research) Chief Executive Fred Hassan said.

Hassan said larger studies were required to show safety.

Others said the FDA had put up roadblocks such as issuing more approvable letters that delay final clearance.

You're seeing almost everything now getting an approvable letter, not an approval, Shire Plc Chief Executive Matthew Emmens said.

Woodcock said she had not looked at figures for this year to see if there was a trend with approvable letters. But she said budget strains put heavy workloads on reviewers trying to meet six- and 10-month review goals.

If people are under time stress, you can issue an approvable letter to extend the review period, she said, adding that increased industry funding cleared by Congress could ease the burden.

But do the problems always rest with the FDA? The chief executive of biotechnology company Onyx Pharmaceuticals Inc, which specializes in cancer drugs, said it comes down to the evidence.

Too many (companies) try to do shortcuts and then blame it on the agency. If you get the data, it's usually not an issue, Onyx CEO Hollings Renton said.

(Additional reporting by Bill Berkrot; Editing by Braden Reddall)