In a fit of anger, drug makers are urging the Food and Drug Administration to delay a final rule giving the agency greater leeway to police off-label marketing over concerns it would harm public health by “chilling valuable scientific speech,’’ according to a recently filed petition.

The rule, issued last month, says drug makers must update product labels if there is evidence a company intended its medicine to be used off label, meaning for an unapproved use. Doctors are free to prescribe drugs for any purpose, but court rulings say drug companies can make statements about off-label uses only if the information is truthful and not misleading.

At issue is a concept known as intended use, which the FDA relies upon for determining when a company intentionally markets a drug for an unapproved use. Two years ago, the agency issued a proposed rule that deleted language indicating a company could be liable for having knowledge of unapproved uses. The move followed years of concern by drug makers over the threat of prosecution.

But the agency “dramatically shifted gears’’ when it released its final rule last month, according to a Feb. 8 petition filed by three groups representing drug makers and biotechs. They argued the final rule gives the FDA too much leeway to gauge how a company intended its medicine to be used, which can then be used to assess whether illegal promotion occurred.

“The open-ended intended use regulations leave manufacturers unable to evaluate, in advance, the lawfulness of proposed business practices,’’ the groups wrote.

And they went on to complain that “the new intended use rule exposes manufacturers to a significant risk of liability for conduct that is entirely lawful and beneficial to the public health.’’

Ultimately, the rule amounts to “a substantial change in the law,’’ the industry groups wrote. They added that the FDA also caused a procedural problem, because there was no opportunity to provide comments before the revised language unexpectedly appeared as a final rule.

In assessing the rule, Jeffrey Shapiro wrote on the FDA Law Blog that “it appears that FDA has now written itself a blank check to find whatever intent it wishes to find, using an unconstrained calculus as to what the ‘totality of the evidence shows.’ ’’ Shapiro is also a director at Hyman, Phelps & McNamara, a law firm that specializes in regulatory law, publishes the blog, and defends drug and device makers.

“The petition cites scientific exchange of information and forecasting, which might include potential off-label use by doctors, as areas where [the] FDA could say those actions are part of a ‘totality of evidence’ that the manufacturer intended to promote off-label,’’ explained Alan Minsk of the Arnall Golden Gregory law firm.

Another attorney suggested the final rule would expose drug makers to another kind of problem False Claims Act lawsuits. Whistle-blowers “will be emboldened to use circumstantial evidence’’ to accuse drug makers of conveying information that causes the government to pay for off-label uses, Benjamin Zegarelli of Mintz, Levin, wrote in a blog post.

The rule emerges amid a heated debate over off-label marketing and commercial free speech.

The FDA has come under sustained pressure from industry to loosen regulations for off-label marketing. Drug makers argue their free speech rights are being restricted and have won significant court battles over the issue. But the agency has regularly voiced concern that public health could be jeopardized if a company distributes information about an unapproved use that has not been proven safe or effective.

The agency held a two-day meeting in November to hash out the issues, and last month it followed up by issuing a 63-page memo. But rather than suggest ways to rework regulations, the agency summarized key points that have framed the long-running controversy, and carefully rebuffed many of the suggestions made by drug makers and others that support expanding pharmaceutical marketing.

For now, there is no indication the FDA will alter its stance. A spokeswoman said the petition is being reviewed.

Ed Silverman can be reached at ed.silverman@statnews.com. Follow him on Twitter @Pharmalot.