For decades FDA regulations have required manufacturers who have knowledge about off-label uses of their products to include such information in their labeling. The agency is now proposing to eliminate the requirement, and attorneys are encouraging firms to take this opportunity to push for further changes to off-label rules.

The agency slipped the proposed changes to its “intended use” regulations into a proposed rule clarifying when products derived from tobacco are to be regulated as a drug, device or combination product. FDA explains in the proposed rule, published in the Sept. 25 Federal Register, that these changes are intended to bring them in line with the tobacco rule.

Attorneys say the change will not have much of an impact on industry since FDA has not enforced this provision. The agency alludes to this fact in the preamble to the proposed tobacco rule saying it is making changes to the intended use regs “to conform them to how the agency currently applies these regulations to drugs and devices generally.”

The agency adds that the changes “would not reflect a change in FDA’s approach regarding evidence of intended use for drugs and devices.”

But the move comes as FDA is facing growing pressure to revise its policies about what is acceptable speech about a drug and could portend further changes by the agency.

“FDA doesn’t usually decide to hamstring its own authority,” Hogan Lovells attorney Susan Lee said. The proposed change “is a tea leaf of the broader debate underway about the way FDA has been determining intended use.”

Amarin Ruling Could Be Incorporated Into Regulation

The “intended use” regulations, included in labeling sections of the Food, Drug and Cosmetic Act, refer to how persons responsible for drug labeling intend a product to be used.

FDA’s proposed revision would delete the sentence: “But if a manufacturer knows, or has knowledge of facts that would give him notice that a drug/device introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug/device which accords with such other uses to which the article is to be put.”

While FDA has had the authority to find intended use based on knowledge alone, Lee said it has not really done so. However, she said there is uncertainty as to what FDA will determine is an unlabeled intended use, and the proposed tobacco rule offers another opportunity to seek clarity from the agency and further changes to the intended use regulations.

For example, she suggested that companies might request that the regulation specify that truthful, non-misleading speech about an unapproved use may not be construed as evidence of intent.

“If this is embedded in regulation it could provide a lot of comfort to industry about their uses,” Lee said.

James Beck, counsel at Reed Smith, also recommended that companies take the opportunity to propose additional changes to the regulation – including calling for portions of the court’s ruling in Amarin Pharmaceuticals Inc.’s First Amendment suit against FDA to be incorporated into the regulation.

Specifically, Beck said the regulation could state that “truthful and non-misleading promotional speech consisting of, for example, summaries and reprints of published studies,” claims approved for similar drugs, and dialogues with doctors about off-label use “is not evidence of objective intent to change an article’s intended use.”

Beck said in an interview that the impact of FDA’s proposed rule “could be huge if companies forced the off-label use issue.”

But even just eliminating the knowledge of unintended use provision would be helpful to industry, particularly in False Claims Act cases, he said. “Drug companies won’t have to look over their shoulder every time they learn of an off-label case.”

Looking To Courts While Waiting For FDA Guidance

Industry has long pushed for FDA to loosen its rules on off-label promotion through citizen petitions, comments and litigation. Firms have scored major wins in the courts. Most recently, a district court judge ruled in August that Amarin may engage in truthful and non-misleading speech promoting the off-label use of its fish oil pill Vascepa (icosapent ethyl) without risk of prosecution for misbranding ([A#14150807002]).

The parties are engaged in settlement discussions, which would enable FDA to avoid an appeal to the US Court of Appeals for the Second Circuit and another ruling that could further restrict its regulation of off-label promotion ([A#14150831002]).

The Second Circuit issued a landmark decision in US v. Caronia in 2012 that the government cannot prosecute manufacturers or their representatives under the FDCA’s misbranding provisions solely for speech promoting the lawful, off-label use of an FDA-approved drug.

The agency is facing another First Amendment challenge in a suit brought in September by Pacira Pharmaceuticals Inc. The company is seeking a court ruling supporting its promotion of the post-surgical pain treatment Exparel (bupivacaine liposome injectable suspension). The case is different from Amarin’s, which involves off-label speech, as Pacira is challenging FDA’s reading of the approved labeling ([A#14150909005]).

In the midst of this litigation FDA is continuing to work on draft guidance for dissemination of information about the unapproved uses of approved products.

FDA missed its original deadline for issuing the guidance by the end of 2014. An agency official noted at a Food and Drug Law Institute conference Oct. 1 that it is still in development and did not indicate when it might be released. He also reiterated the agency’s plan to hold a public meeting on off-label promotion after the draft guidance issues ([A#14151002002]).

In the meantime, companies can submit comments on the tobacco proposed rule. Comments are due Nov. 24.

FDA Off-Label Reg Changes For Drugs Could Be Driven By Tobacco Policy

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