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In July, 2011 we posted about the post-Sorrell citizen petition that seven major drug companies filed with the FDA concerning the Agency’s restrictions on truthful off-label promotion.

On June 6, 2014, the FDA “granted” the petition.  It’s nothing like D-Day, however.  Nothing earth-shattering here.  The FDA’s “grant” is more like a “dodge.”

That being said, the FDA’s response is still interesting, sometimes as much for what the Agency didn’t say as for what it did.  The petition dealt with the FDA’s convoluted regulatory positions on four situations involving the dissemination of medical and scientific information about off-label uses:

  1. Manufacturer responses to unsolicited requests;
  2. Scientific exchange;
  3. Interactions with formulary committees, payors, and similar entities; and
  4. Dissemination of third-party clinical practice guidelines.

FDA Response at 2.  The petitioners also asked in a 2013 supplement (that is, after the Caronia decision) “that [FDA] provide clear interpretations of key definitions to assure that our regulatory scheme better aligns with . . . the limitations under the First and Fifth Amendments.”  Id. at 3.

The FDA’s response started with a “background” section laying out its view of the FDCA’s “framework.”  The FDA views the FDCA and its regulations as “collectively prohibit[ing] manufacturers from introducing new drugs into interstate commerce for any intended use that FDA has not determined to be safe and effective.”  FDA Response at 3.  The FDA reiterated its cobbled-together multi-regulation (depending on “adequate directions for use”) justification for why off-label promotion changes a product’s “intended use.”  Id. at 3-4.  Nothing new there.  Unfortunately, the FDA still didn’t give any definition of what “promotion” is, which (even if we disagreed with the outcome) would at least have added some clarity to the situation.  Rather, the FDA stayed with its maddeningly obscure, and by now quite judicially shopworn, “intended use” formulation based on regulations that haven’t been updated in over 50 years (despite the Supreme Court’s 1976 recognition of “commercial speech”).

After reiterating its regulatory position, the FDA gave its view of congressional purpose:

In developing the statutory framework described above, Congress intended to curb the distribution of unsafe and ineffective medical products in the market, by requiring manufacturers to investigate and substantiate the safety and effectiveness of medical products for each intended use before offering the products for sale to the public.

FDA Response at 5.  Supporting this view, the Agency discussed the 1962 amendments to the FDCA that created the current New Drug Application system.  Id.  The FDA quoted testimony from a government official – not a House or Senate report, or even the statement of any individual member of Congress – in support.

We think that’s a bit of a stretch, for several reasons.  First, what the FDA quoted doesn’t qualify as what any court would consider to be legislative history.  Second, the language of the FDA’s “intended use” regulations pre-existed the 1962 amendments.  Most importantly, we don’t think that the 1962 amendments ever mentioned “intended use.”  We searched the text of the current FDCA (not a perfect match, but easy to do), and found not a single instance of the statute – even now – using the “intended use” concept for a drug.  We found a couple of references for devices (which could be no earlier than 1976), but most of the occurrences of the term in the statute are far more recent amendments concerning animal drugs or food additives.  In our view, Congress has never validated any aspect of the FDA’s “intended use” regulatory approach as to drugs generally, nor in the 1962 amendments specifically.

Moreover, assuming this was Congress’ intent, it could be furthered is at least equally – if not more – by requiring that widespread off-label uses be tested and the results submitted to the FDA.  The Agency, however, has never gone this route, even though it would have none of the free-speech problems  associated with its current off-label promotion ban.

But that’s just our view.

Then the FDA finally got around to off-label use:

Information that emphasizes the drugs’ claimed benefits, while minimizing the drugs’ limitations and adverse effects, may inappropriately influence a physician’s prescribing decisions in a manner that is not in the patient’s best interest.  Even widespread acceptance of an unapproved use in the medical community is no guarantee that the drug is safe or effective for that use, and is no substitute for the rigorous clinical trials, FDA-approved labeling, and careful scrutiny by FDA that the drug approval process requires.

FDA Response at 5-6.  The Agency dropped a footnote citing a study from 1991.  Id. at 6 n.9  We certainly agree with the FDA here, first that misleadingly biased information can be harmful, and second, so can some off-label uses.  However, the risks of biased information don’t justify a ban on truthful information.  Also, that the FDA had to reach back more than 20 years to find its example suggests that the great majority of widespread off-label uses are, in fact beneficial – that’s why they achieved broad medical acceptance in the first place.

Next the FDA spoke of “harmonizing” First Amendment interests.  The Agency considered it “important” that “the current regulatory framework . . . has been developed over time in response to public health tragedies, particularly those that occurred when manufacturers could distribute drugs and devices without independent review of scientific evidence of the products’ safety and efficacy.”  FDA Response at 6.  But that view would suggest that off-label use should be banned – an alternative Congress has expressly rejected.  See 21 U.S.C. §396.  The FDA plays an “important” role in approving products and their labeling.  FDA Response at 6-7.  Damn right.  That view supports preemption.

Then the FDA recognized the value, not only of off-label use but of accurate information concerning such uses – from our perspective, the best part of its discussion:

The Agency has recognized − and continues to recognize − that there can be utility in the dissemination of truthful and non-misleading scientific or medical information regarding off-label uses under appropriate circumstances. . . .  [A]any individual patient may have characteristics and needs that deviate from the patient population for which a medical product is indicated.  Thus, FDA’s regulatory framework also recognizes the role that medical professionals play in making treatment decisions for individual patients; this recognition is embodied in FDA’s long-standing recognition of the practice of medicine and in the device-specific “practice of medicine” provision of the FD&C Act, section 1006 (21 U.S.C. 396).  In general, FDA does not seek to regulate the practice of medicine, including the off-label use of legally marketed drugs and devices for individual patients.  Indeed, for some health conditions, off-label uses of medical products have made valuable contributions to patient care.

FDA Response at 7 (emphasis added).  Unfortunately, while the FDA saw fit to footnote an example of unsafe off-label use (from 20+ years ago), it didn’t give equal time to beneficial off-label uses.  That omission is not hard to rectify.  There’s one mentioned in the June 10, 2014, FDLI Smart Brief (see “Global Focus”), about which you can read for free here.

But just as things might get interesting – with the Agency listing the factors it sought to “harmonize” (FDA review of products, public health and safety, value of disseminating information, and constitutional concerns)  − the FDA ended its discussion of the issue.  FDA Response at-8.  Instead, the Agency moved on to its “initiatives.”  Id.  Although admitting that its current “draft” guidances “do not as of yet provide a comprehensive answer,” the FDA asserted “that issuing guidance initially to address industry questions is an effective first step.”  Id.

Only if the agency wants to avoid judicial review of its positions that would come with issuing real regulations.

Which it does.

Instead of committing to issue real regulations, the Agency touted recent draft guidances on dissemination of scientific information (2011), unsolicited requests for information (2011), and good reprint practices (2014).  FDA Response at 8-9.  We discussed the latter two here and here.  Amidst all this bureaucratic self-congratulation, we do learn some news:

FDA plans to issue guidance that addresses unsolicited requests, distributing scientific and medical information on unapproved new uses, and manufacturer discussions regarding scientific information more generally, by the end of the calendar year.  FDA also plans to issue draft guidance documents that address your remaining requests involving health care economic information by year-end.

FDA Response at-9 (emphasis added).  It’s unusual to see the FDA set a deadline for itself, particularly since it has a habit of blowing through even congressionally mandated deadlines.  It did so here, so we can look forward (if that is the word) to final guidances before 2015 rolls around.

But in the end, the FDA didn’t respond to the main thrust of the citizen petition and its supplement, which is for a constitutional evaluation of the FDA’s propensity for banning truthful speech concerning off-label uses.  In the end, we’re left with:

We believe that the guidances we have issued and plan to issue in the next year will provide the clarity you request in both petitions on those topics.

FDA Response at 9.  All we get concerning the First Amendment is:

We recognize the evolving legal landscape in the area of the First Amendment, and we are reviewing and analyzing the Agency’s policies, guidance, and regulations in this area more broadly.  Id. at 10.  In other words, still more agency bobbing and weaving.