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FDA Hardens Its Stance on Intended Use and Off-Label Use and Industry Responds

From 2015 to 2016, FDA appeared to open the door to loosening the standards around intended use and off-label use, but recent rule-making and public comments suggest that FDA is becoming more sclerotic instead of flexible. However, given the political climate in the federal government and the lack of an appointed FDA commissioner, it is unclear whether FDA will hold its ground or be forced to retreat.

Intended Use Changes and a Citizen’s Petition

As we reported last month, on January 9, FDA released a final rule amending established regulatory definitions of “intended use” for drugs and devices to replace a directive that a manufacturer must add labeling addressing unapproved uses known to the manufacturer but, also, with one requiring similar labeling if a manufacturer objectively intends, based on a “totality of evidence,” to promote a medical product for an unapproved use. The final rule caught the pharmaceutical and medical device industries off-guard since the proposed rule, issued on September 25, 2015, simply deleted the knowledge-based labeling directive without hinting at a change to a totality-of-evidence standard.

On February 8, on the day the final rule was slated to take effect, industry association groups responded by filed a citizen’s petition under 21 C.F.R. §§ 10.33(b), 10.35(b) to demand that FDA stay and reconsider the final rule. The petition claims that FDA’s significant change to the intended use definitions in the final rule violated the Administrative Procedure Act because interested stakeholders were not given the opportunity to comment on the revised definitions.  It also undercuts FDA’s reasoning for implementing a totality-of-evidence standard, stating that such a standard is overly vague and is not supported by relevant case law.

Among the consequences resulting from the revised definitions, the citizen’s petition states that the open-ended, subjective totality-of-evidence standard will result in:

  1. increased False Claims Act litigation because qui tam relators will be emboldened to use circumstantial evidence to allege that manufacturer communications caused the government to pay for off-label uses of medical products; and
  2. a chilling of free speech about legitimate scientific data related to off-label uses of medical products.

Although many qui tam False Claims Act complaints include claims based on circumstantial evidence, it is not clear that FDA’s change to the intended use definitions will have much effect on the outcome of such cases.  In 2016, two qui tam cases involving off-label claims—U.S. ex rel. Colquitt v. Abbott Laboratories and U.S. ex rel. Polansky v. Pfizer, Inc.—were rejected by different courts, in part, because the supposed off-label communications were not sufficiently established as the cause of the alleged false claims.  Notably, the U.S. District Court for the Northern District of Texas instructed the jury in the Abbott Labs case that “[e]vidence, if any, of off-label promotion or alleged violations of [FDA] rules . . . do not, in and of themselves, establish liability under the False Claims Act.”

However, the chilling of communications on scientific data could turn out to be a significant concern, depending on the outcome of FDA’s deliberation over its position on manufacturer communications on unapproved uses and the First Amendment protections afforded by recent court battles (U.S. v. Caronia, U.S. v. Vascular Solutions, Inc. and Amarin Pharma, Inc. v. FDA).  Which brings us to the next set of developments . . .

FDA Goes Defensive on Off-Label Use

After holding a public meeting to hear stakeholder positions on manufacturer communications of unapproved uses for medical products (which we reported on here), FDA kept the docket open for comments until January 9, 2017 in order to receive comments related to the meeting. However, FDA reopened the comment period on January 19, citing criticism from stakeholders that the Agency did not sufficiently address First Amendment issues related to off-label communications.  At the same time, FDA released a memorandum describing the Agency’s baseline position on relevant First Amendment case law and various proposals to address off-label communications—and it’s pretty bleak.  FDA comes off as defensive in the memorandum, describing the Agency’s duty established by Congress to protect the public health, defending its previously established policies, undercutting recent First Amendment rulings, and systematically rejecting twelve separate proposals to expand or contract regulation of off-label communications.  Given the lack of apparent flexibility, the memorandum appears to paint FDA as dead set against changing its off-label policies.

But Political Decisions Could Reverse FDA’s Positions

These developments have come about during a time of uncertainty at FDA. The Agency is without an appointed commissioner and Congress is still mulling the use of the Midnight Rules Relief Act to undo regulations enacted during President Obama’s time in office (discussed here).  On the one hand, President Trump is considering unconventional candidates for FDA Commissioner, and appointment of a market-minded business person (like Jim O’Neill) could move to break down FDA’s longstanding prohibitions against off-label promotion.  On the other hand, Congress could reverse FDA’s final rule amending the intended use definitions, making the citizen’s petition moot.

Although it is difficult to predict whether FDA’s recent positions will stand in light of political uncertainty, it is almost certain that FDA policies will change based on upcoming decisions by the Executive and Legislative branches.

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Benjamin advises pharmaceutical, medical device and biotech companies on the FDA regulatory process to identify the correct regulatory pathway, assisting with FDA communications and strategy.