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I am Doug Hallward-Driemeier, a partner in the Washington D.C. office of Ropes & Gray and Chair of the Firm’s Appellate and Supreme Court Practice. Today, I am joined by Life Sciences partners, Kellie Combs and Greg Levine, to discuss three key documents recently issued by FDA related to manufacturer communications. In the last days of the Obama administration, FDA issued draft guidance about communications that are “consistent with FDA-required labeling” as well as draft guidance about manufacturer communications with payers, formulary committees and similar entities. At the same time, the Agency also published a memorandum addressing First Amendment considerations related to its regulation of manufacturer speech, which FDA framed as a follow-up to the public hearing that the Agency held last November and that we discussed in an earlier podcast.

Doug: Kellie, you testified at the hearing on behalf of the Medical Information Working Group, a coalition of thirteen drug and device manufacturers seeking to change FDA’s regulatory scheme. What is your reaction to the First Amendment memo?

Kellie: Doug, at the hearing, I and many others expressed some concern that FDA hadn’t adequately addressed First Amendment issues in the notice announcing the hearing. And the First Amendment memorandum is clearly a response to those concerns, but what you see is essentially a sixty-three page justification of the status quo. The Agency continues to struggle with the impact of these recent First Amendment cases, Caronia, Sorrell, Amarin and others, and throughout the memo there is an emphasis paid to false and misleading promotion and the harms that can be caused to patients as a result. What you don’t see in the memo is FDA paying much attention to truthful and non-misleading scientific exchange, which is really what the industry has been asking for clarity on for all these years. Now, of course, the memo was issued on the last days of the Obama Administration and it remains to be seen how a Trump Administration would view the memo. Doug, let me turn it back over to you now. You and I have worked together for a long time on these issues involving FDA promotional rules and the First Amendment. What caught your eye about the memo?

Doug: Well, to some extent, I think the Agency is still in denial about the significant developments in the First Amendment area as it relates to the regulation of manufacturers’ speech about their products. In my field, you know that you are in trouble when the best authority you can cite are the dissenting opinions, and very often in this memo I see FDA citing to the dissents in Sorrell and the dissent in Caronia, but I did think that it was very significant that they confirm that off-label uses are very important to providing the best medical care for patients and that information about off-label uses is very important to provide to health care practitioners so that they can make the best decisions about the medical care for their patients. I think that the Agency just doesn’t appreciate the extent to which when they say that it’s important that that information be shared by third parties, but we’re going to restrict it when it comes from manufacturers that that type of speaker-based discrimination, is something that the First Amendment just really condemns. And I don’t think that it’s enough to simply point out as FDA does that manufacturers have an economic interest. I think almost everybody in this area has an economic interest of some sort, and in the Sorrell case, the Supreme Court specifically said that that wasn’t a sufficient basis to restrict manufacturers’ speech in ways that other speakers were not restricted. But I know that this is not going to be the last word on that so we’ll have other opportunities no doubt to speak about it. But Greg, I wanted to turn it over to you to talk about some of the draft guidance. I know that you’ve advised clients for many years on questions involving off-label promotion. So in your view, what were the key takeaways from the draft guidance about communications consistent with the FDA label?

Greg: That draft guidance I think is a very useful guidance because the prescription drug labeling regulations for many years have said that a manufacturer can disseminate information that is consistent with the FDA-approved labeling for the drug, but there has never been any clarity from the FDA on what that actually permits the manufacturer to do. In practice, you know, a lot of the times when the FDA either if it is describing its policies or actually dealing with manufacturers in specific instances, would take a pretty strict position, and if something isn’t in the approved labeling for the drug, then you are not allowed to talk about it in a promotional context. So this is really the first time where FDA has kind of laid out its thinking, they give a number of examples of the types of information that can be consistent with approved labeling. One which I always thought in my mind was the kind of information that you could disseminate was when you have information on longer-term use of a drug compared to what you had at the time of approval. So if you have a product that’s approved for chronic use, it doesn’t have any limitation on its permitted use period and at the time of approval you had data on 12 weeks of use for example and that is what’s in the labeling in the clinical study section of the labeling. If you have later data from a study on longer period of use for six months of use or 12 months of use, that you can disseminate that information. So they’ve made that clear here and they’ve given a number of examples of where information would be consistent with the labeling. So I think that is useful guidance to have, and this is the first time that they’ve ever addressed this issue explicitly in the context of medical devices, so this is the first time the device manufacturers would have guidance from the FDA. And they talk about not only PMA-approved devices but also 510(k) and de novo exempt devices so I think it’s useful in that score as well.

There are some interesting aspects of the guidance. One is that the guidance appears to be backing off from the long-standing position FDA has had that a comparative claim for a drug product requires substantial evidence in all cases and that the FDA’s interpretation in the past has been that that’s two adequate and well-controlled head-to-head studies. And so in this guidance, they say if you have a study that may be sufficient. In addition, in the guidance they seem to be moving towards substantiation of claims based on competent scientific evidence. So they do talk about the fact that the studies that support the information that you disseminate must be adequate and scientifically sound and sufficient to support those claims, but they don’t insist that every claim that you make that’s information outside the labeling but consistent with labeling be supported by evidence of the same standard that’s required for approval. So that would be substantial evidence for a new drug or a valid scientific evidence for a device, but they just talk more generally about scientific support being valid to support the claim.

Doug: One of the things that I noticed about it, and you’ve already touched on, is the way in which FDA seems to have made more permissive the standard for making comparative claims and that it doesn’t necessarily have to be supported by substantial evidence. Bu what I find problematic from a First Amendment standpoint is the fact that there is still a regulation on the books that says the comparative claims can only be made when supported by substantial evidence. And then we have this non-binding guidance that suggests that, well, you can go ahead and do that. From a First Amendment standpoint, to have a rule that says “thou shalt not speak,” but then at our discretion we will allow you to speak, that’s not consistent with what I think the First Amendment and the Constitution command. Are there other ways in which you felt that the guidance wasn’t as clear as you would have liked?

Greg: I think there are probably several ways in which the guidance can be clarified, but one that struck me is that the rubric that they set out here, they set out several factors that you would analyze in determining whether information is consistent with the information in the FDA required labeling as they referred to in the approved labeling for the product. I think that that rubric could be applied to a situation where you’re describing a specific use of a product that is more specific than what the approved indication is. If you have a more general indication for either approved for a drug or for a device, and this issue comes up quite frequently in the device context, if you want to disseminate information on a more specific use of that product, I think the factors in this guidance can be used for that analysis but they never in this guidance document talk about the specific vs. general issue even though the existing guidance on that question is either non-existent or not very good. So I think it will be useful in the final guidance if they would be explicit and say that you can use this analysis in this guidance to analyze that question specific vs. general.

Doug: So Kellie, let’s turn now to the payer guidance, I know that the industry has been asking for this guidance for years now, so is this a win for industry?

Kellie: It’s absolutely a win for industry because you have FDA for the first time weighing in here and providing some clear recommendations on how manufacturers can move forward in a permissible way. But FDAMA 114 has been on the books now for almost 20 years, and this is the first time FDA has weighed in with its interpretations of what key terms in the statute mean, such as, to whom can health care economic information be provided, how would the Agency interpret terms like the competent reliable scientific evidence standard. And then with respect to pre-approval communications, the Agency says very clearly that those recommendations applied not just to drug manufacturers but to device manufacturers as well, which is significant.

You know, I think with respect to the FDAMA 114 part of the guidance, in many ways the Agency’s recommendations validate what manufacturers have been doing for a long time in this space and validate the legal interpretations of FDAMA 114 that industry has put forward previously. And then with respect to the pre-approval communications part of the guidance, that also is relatively straightforward, you see the Agency moving forward with principles that look very similar to scientific exchange principles. Manufacturers can share data so long as it is shared in a truthful and non-misleading way and certain disclosures and disclaimers accompany the communication. I think that is all very helpful. One disappointing aspect of the guidance is that the pre-approval part of it only applies to products that have never been approved or cleared for any use, and the Agency says very clearly that when you’re talking about approval for a new indication, that that’s outside of the scope of the guidance. I think that is disappointing and the Agency takes the position there that manufacturers should be disseminating reprints or responding to unsolicited requests, not even recognizing that scientific proactive exchange or other avenues may be appropriate.

Doug: Well, I know that there will be many further questions as well as deeper insights as we gain a greater familiarity with these new guidances. But that is all the time we have for now. Thanks very much Kellie and Greg for your insights and thank you for listening. Please visit the Capital Insights and FDA Regulatory pages at www.ropesgray.com for news on developments in the drug and device industry, as well as information on what changes may be in store for the health care and life sciences industries in the new Administration.