- Speech by
Lowell Schiller, JD
Principal Associate Commissioner for Policy - Office of Policy
Thank you for having me here today.
It’s an honor to speak with you this morning at the Food and Drug Law Institute’s annual conference on medical product advertising and promotion. Each year, this event brings together a broad range of stakeholders to discuss what’s happening in this space. There’s a lot to talk about.
Looking at the agenda for this year’s conference, I see there are sessions planned on many timely issues. And looking around this room, I see many people here from across industry, and in government, private practice, and the scientific and public health community, to take part in these discussions and to learn about the latest trends and developments.
There’s a reason why so many of us gather each year to wonk out on advertising and promotion. Part of it is that there are many emerging or recurring issues that are difficult or complex, and worth our time to consider and discuss in depth. But that’s not the whole story.
This kind of engagement, year after year, reflects a shared commitment to complying with the law, and to getting it right, in letter and in spirit.
Another part of the story goes to why it is that we have a widely shared culture of compliance, and why it is that so many members of industry care about getting it right. And the answer isn’t just that people are afraid of legal sanction.
We operate in a space where many of the core principles of our legal framework are undergirded by widely shared, foundational values.
Medical products aren’t just widgets. These are products that can save people’s lives, prevent or cure terrible diseases, help people manage difficult or painful conditions, and otherwise improve health and well-being. And patients rely on all of us, with our various roles across the overall system, to make sure that the medical products they use or are given are safe and effective, and that they are appropriately labeled and promoted.
Many of the rules governing medical product advertising and promotion go to the heart of our system of protecting patients and the public health. And those rules are built on a foundation of values that I believe are broadly held and agreed upon.
Let me give a few examples.
First, I think there’s broad agreement that false or misleading statements about a medical product can put patients at risk and are completely unacceptable.
Second, I think there’s also broad agreement that a medical product generally should be approved, cleared, or licensed by the Food and Drug Administration (FDA) for each of its intended uses before it is marketed for such use. This general requirement is one of the cornerstones of FDA’s public health mission, and for good reason.
When a medical product has been approved, cleared, or licensed for its intended use, Americans can have confidence that it has undergone a rigorous scientific and medical review to ensure that it works correctly and that its health benefits outweigh its known and potential risks for that use. This protects patients against quackery and fraud, and it provides patients and health care providers the information they need to use medicines wisely and appropriately. It also helps motivate the development of robust scientific data on safety and efficacy.
Third, I think it’s widely acknowledged that there can be significant value in a manufacturer’s truthful and non-misleading communications about its medical products, including (but not limited to) some communications that aren’t strictly limited to the information included in the product’s FDA-approved labeling. At the same time, some communications – including communications in which a manufacturer promotes its product for a use that has not been approved, cleared, or licensed by FDA – can undermine the FDA review and approval process and put patients at risk.
Fourth, I think most would agree that it’s important to have appropriate guardrails, enforced by FDA and others, to protect patients and the public health.
Of course, there’s room for debate about what those guardrails should look like, where various lines should be drawn, and how to balance objectives that sometimes can be in tension. In fact, many of the conversations at this conference are likely to revolve around these kinds of questions.
The reason why we can have these conversations, and why so many of us believe it’s important to have these conversations, is because of our commitment to shared values such as the ones I just described.
But here’s the thing: Although these values are widely shared, they aren’t universal.
I’m not talking about good faith debate regarding how best to protect and promote the public health. I’m talking about bad actors who are all too willing to endanger consumers by selling harmful products that often are not FDA-approved for any use, and that often aren’t manufactured in accordance with any appropriate standards.
In many cases, these are parties who work actively to deceive their consumers into believing that the products they’re selling are safe and effective for some use, when in fact there aren’t data to support that use, or the data actually refute it. In other cases, parties may try to prey on consumers who have misperceptions about the benefits and risks of certain types of products, by selling them unapproved articles that may be inherently dangerous, contaminated, or otherwise unsafe.
This is exactly the kind of quackery and fraud that FDA was established to guard against. And though we’ve managed, to a large degree, to eliminate it from the more mainstream and legitimate parts of industry, there’s still far too much of it. It lives, for example, in corners of the internet, where consumers can be reached directly. And sometimes we even see it creeping into more mainstream outlets, with even broader dissemination.
So why am I raising these concerns at this conference, when just a moment ago I explained that this event is an opportunity to discuss issues from a platform of shared values –values that these kinds of bad actors reject?
It’s because the conversations at conferences like this don’t take place in a vacuum. When it comes to many of the issues bearing on medical product promotion, you can’t have a complete and fully productive discussion about the right approach to regulating parts of industry that care about legal compliance, and that care about the public health, without also taking into account the potential impact on our ability to address misconduct by bad actors who don’t care about those things in the same way.
It’s not enough for us to consider how a regulatory framework or approach will apply to the more legitimate parts of industry who generally try to comply. We also need to consider what impact those policies may have on our ability to identify and address misconduct, and to interdict dangerous products that threaten public health and safety.
We don’t have one set of rules for those who generally try to comply with the law, and another set of rules for those who try to skirt it. Our rules need to work across the full range of actors to whom they apply – even when bad actors are trying to operate wholly outside of the relevant regulatory regime.
Let me give an example. Suppose there’s an import at one of our ports of entry, and it contains articles that haven’t gone through the drug approval process, and that aren’t the subject of an over-the-counter monograph, but it appears that they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body. The articles may even bear false labeling, such as statements that they are “not for human consumption” or “for research purposes only,” when through other evidence it’s apparent that’s not the case.
Depending on the facts and circumstances, there may be a variety of grounds on which such articles should be denied entry. And many of the statutory provisions that could be implicated are many of the same statutory provisions that could be implicated in other settings by the inappropriate promotion of an approved drug.
And this raises a challenge – not just for FDA as regulators, but also for those outside the Agency who may advocate for various regulatory approaches.
How do we maintain a framework that makes sense for all the diverse activities that it touches?
At this conference, I’m sure there will be many conversations about various policy options that might allow space for potentially valuable activities by legitimate and presumably well-intentioned manufacturers. As we discuss such options, one thing we need to consider is what space any given option might create for potential bad actors to put the public at risk.
What will a policy mean for the U.S. government’s ability to identify violations, or to interdict dangerous products? Will the process be workable and efficient as we identify potentially illicit articles in the field? And, at the same time, we need to consider how the tools and authorities we may use to address the worst violations might affect more legitimate parts of the market.
We also have to recognize that we’re seeing increasingly sophisticated behavior from many of those who seek to market unapproved products that they intend for use as drugs or other medical products.
For example, some of the easiest violations for us to identify and address are ones in which the unapproved use is stated directly on the packaging, or in other obvious places like a product website. Statements like:
- “Cures cancer”;
- “Prevents Alzheimer’s”; or
- “Treats pain or opioid use disorder.”
We see all too many violative products that fit this mold. But as time goes on, we also are seeing more products that avoid making these kinds of statements.
Perhaps the target customers are familiar enough with the product or substance that its manufacturer doesn’t feel the need to make express claims about what it does. Perhaps some manufacturers have come to believe that they can rely on other people’s statements to inform their consumers.
Whatever the rationale, we are seeing increasing numbers of unapproved products that strip express claims out of their labeling but that still appear to be marketed for intended uses that fall within FDA’s jurisdiction. In some cases, products may even be labeled with non-medical product uses or disclaimers that strain credulity but appear to be attempts to evade FDA jurisdiction.
If, for example, you have an herbal product that you used to market for pain relief, but that now you are labeling as potpourri, you’re not fooling anyone. But the questions we have to ask include:
- What evidence do we need to establish that this product is a drug within our jurisdiction?
- What kinds of resources will we need to develop that evidence?
- And what kinds of incentives are being created for bad actors to try to skirt our authority through fraud or deception?
Often in such cases, there’s still plenty of evidence – of types that FDA has a long history of relying upon –to establish that a particular article is intended for use as a drug or other medical product, and that it falls within our jurisdiction. And often, this is still a straightforward inquiry.
But in some cases, depending on the particular circumstances, the inquiry can be less clear cut. And the more resources we have to invest, and the more we have to contend with contestable facts, the more it becomes challenging to interdict dangerous substances – at the border, or in domestic commerce. That’s not an acceptable outcome, particularly in the context of a nationwide epidemic of addiction and abuse of opioids and other substances.
At the same time, we need to be thoughtful about how our approach to these types of violations fits within our overall framework for identifying unapproved new drugs, or certain misbranding violations – not just for products not approved or cleared for any medical use, but for approved medical products that might be marketed unlawfully.
We’ve acknowledged as an agency that there’s space for appropriate and potentially valuable discourse about approved medical products, beyond just a recitation of what’s in the FDA-required labeling. We need to be thoughtful about how to maintain that space while also maintaining our ability to aggressively pursue violations that put the public health at risk.
I expect there will be many interesting conversations at this conference about some of these tangled interests, and thoughts about approaches to disentangling some of them. What I’d like to focus on today are several approaches that may, in some cases, help to cut through the knots altogether.
The first approach is legislative. Recently, we’ve seen Congress step in to grant FDA new tools and authorities to stop dangerous substances – tools that allow us to assert jurisdiction over products without having to engage in potentially resource-intensive exercises to evaluate intended use, and that we can exercise without raising implications for how FDA evaluates intended use in other settings.
A perfect example is in the SUPPORT Act.
This new law, which the President signed in October of last year, is a critical element of our nation’s actions to address the ongoing opioid epidemic, and it includes a variety of measures to improve the availability of treatments for opioid addiction and to improve the government’s ability to stop the trade of illicit drugs.
The SUPPORT Act granted FDA a number of new authorities to help us more efficiently and effectively interdict dangerous substances being offered for import. I’d like to focus on one of those new authorities in particular – section 3022 of the SUPPORT Act, which added new section 801(u) to the federal Food, Drug, and Cosmetic Act, or FD&C Act.
This new authority allows FDA to treat certain imported articles as drugs when they enter the country through international mail facilities (IMFs), and to stop them as appropriate, based on what substances are in them. And FDA can use this authority without evaluating other evidence of intended use.
Specifically, if an article that arrives through an IMF is an ingredient that presents significant public health concern and is or contains an active ingredient that’s found in an FDA-approved drug or licensed biologic, or certain investigational drugs or biologics, then FDA can treat it as a drug. The same goes for an analog of such an active ingredient.
After we received this authority, FDA set to work to establish new procedures to implement it. And in March of this year, we began using it to detain – and in most cases destroy – dangerous and illicit substances being offered for import through the international mail facilities.
This new authority has been an incredible success. Through the month of August, FDA staff in the IMFs applied this new authority to refuse admission to over 8,300 products, representing 42% of the drug products encountered in IMFs during that time. About 7,300 of those 8,000+ drugs have either been refused and destroyed or are being processed for administrative destruction, reflecting an 88% destruction rate.
That’s over 8,000 products that raised significant public health concern that we were able to keep out of the country without having to engage in potentially resource-intensive inquiries into their intended uses. And that’s over 8,000 products for which the lawyers in this room don’t need to analyze our refusal determinations to see if there are broader implications for medical product promotion.
In my view, that’s a win-win. Except maybe for those of you who lost out on a few billable hours.
This is hardly the only example of Congress granting FDA authority over a product based on its composition or characteristics, without requiring a broader inquiry into its intended use. Here are a few other examples:
Section 301(ll) of the FD&C Act makes it a prohibited act (subject to a few limited exceptions) to add a substance into food if that substance has been approved as a drug, or if that substance has been the subject of substantial clinical investigations, the existence of which has been made public.
For purposes of this prohibited act, it doesn’t matter why the drug substance was added; all that matters is that it’s present. If, for example, a national restaurant chain were to start selling burgers with approved blood thinners in the special sauce, or milkshakes containing approved chemotherapeutic drugs, we wouldn’t need to ask about the intended use. It would be illegal – and dangerous.
In addition, the definition of “dietary supplement” contains elements that look to the substance itself, as opposed to its use. For example, for a substance to qualify as a dietary supplement, it must contain at least one of several enumerated dietary ingredients.
And, similar to the prohibition on adding certain drug substances to foods, a product is generally excluded from the definition of a “dietary supplement” if it contains a substance that has been approved as a drug or licensed as a biologic, or a substance that has been the subject of substantial clinical investigations for such uses, if the existence of such investigations has been made public.
My point in recounting these examples is that Congress has demonstrated that there are ways to grant FDA authority to protect the public health that don’t require the Agency to address potentially complicated questions of intended use before doing so. And, in limited, appropriate circumstances, granting such authority can provide significant benefits – by enabling FDA to protect the public health more effectively and efficiently, and by limiting some of the potential for actions in one area to have ripple effects in other parts of our portfolio.
As we move forward, we should be asking if there are additional, targeted opportunities (like those Congress addressed in section 3022 of the SUPPORT Act) where similar legislation might make sense – narrow circumstances in which the public health would be better served if FDA could act without having to dedicate resources to analyzing intended use, and where the broader intended use framework might benefit from carving out these cases.
There’s one such potential opportunity that I’d like to discuss today. It relates back to something I discussed a moment ago – the definition of “dietary supplement.”
As I just said, substances that contain certain drug ingredients are excluded from the definition of “dietary supplement.” This is similar to the prohibition on putting certain drug substances in foods, but with the critical difference that it’s not a prohibited act; it’s just an exclusion from the definition of “dietary supplement.”
This distinction can lead to anomalous results. In many cases, a product that’s labeled as a dietary supplement, but that contains a drug substance, will actually be a drug, not a dietary supplement.
For example, sometimes we will see products that are marketed as dietary supplements with express claims for male enhancement, but it turns out that the secret ingredient is undisclosed sildenafil (i.e., Viagra). In such cases, the product is a drug, and that will be a fairly straightforward determination for us to make.
But in other cases, establishing that a product mislabeled as a dietary supplement is actually a drug may be more complicated. For example, if a drug substance is mislabeled as a dietary supplement, but there are no express claims, then we need to ask what evidence might establish that the product is intended for use as a drug. Depending on the facts, this could be resource-intensive or otherwise challenging.
One way to help address this issue would be to move the drug substance exclusion out of the definition of “dietary supplement,” and make it clear that the presence of such substances in a dietary supplement renders the product an adulterated dietary supplement – which would be in addition to any other potential violations. The universe of what could be a lawful supplement wouldn’t change, but FDA would be able to move against unlawful and potentially dangerous products containing drug ingredients without having to engage in a new intended use inquiry.
Like I said earlier, targeted legislative updates like this, or the SUPPORT Act, can help to cut through some of the knots that we find in our broader framework governing medical product communications.
Another approach to cutting knots involves technological innovation. In particular, I’d like to focus on real-world evidence, by which I mean evidence from data that are routinely collected about a patient’s health, which can tell us about the use of a medical product, or its potential benefits or risks. Such evidence can be derived from a variety of sources, including electronic health records, medical claims and billing data, data from product and disease registries, patient-generated data, and others.
Properly harnessed and utilized, real-world data can help advance our knowledge about a medical product, often much more quickly than could be done through a traditional clinical trial. As we learn more about marketed medical products, the body of information about a product may grow well beyond what FDA considered when approving or clearing that product’s labeling.
This can contribute to a better understanding of the medical product, and it leads to questions about when and how such new information can be incorporated into a product’s approved labeling.
To that point, real-world evidence can be an important tool to help support earlier approval decisions for potential new indications, new patient populations, or other new labeling information. By increasing the efficiency of evidence generation, real-world evidence can potentially help to support earlier expansions to a product’s labeling. This can help to advance the public health in many ways, not least of which is reducing the amount of time during which new information is available but there has not yet been an approval decision.
At FDA, we’re working hard to advance real-world evidence as a tool to support innovation and our own regulatory decision-making. For example, last December we published a framework for evaluating the potential use of real-world evidence to help support the approval of new indications for approved drugs, or to help support or satisfy post-approval study requirements for approved drugs.
This past April, we saw a good example of how this can work in practice when FDA approved expanded indications for a breast cancer drug to include men. The safety and efficacy of the drug had been previously demonstrated in women, and the real-world data developed from electronic health records and post marketing reports of the drug’s use in male patients supported the extension of the indication to men.
Approvals like this are exciting, and in the years ahead we hope to be able to support more decisions about expanded indications using similar types of real-world evidence. Over time, we hope to see more of this type of information run sooner through our approval process, and perhaps in some cases to see less of a spread between the emergence of potentially promising new information and a regulatory decision based upon it.
At this point, I want to turn back to something I said earlier, which is that the medical product industry benefits from a broad culture of compliance, and from a widely shared commitment to protecting and promoting patient and public health.
I spoke earlier about an exception to that general commitment – various bad actors who don’t care about compliance with the law, or who use the law as a shield to try to evade the consequences of their noncompliance.
But before I close, there’s another exception I want to discuss, which falls into the category of gamesmanship by people who should know better but are trying to protect their market share.
We have a system that tries to balance the goals of innovation and competition. It does this by granting patents and periods of market exclusivity to incentivize innovation, but keeping these periods limited in time so that after a phase of higher return on investment, the market opens to competition – hopefully robust – that can take advantage of FDA’s determinations of safety and effectiveness for the innovator product to bring follow-on products to market more efficiently and cost effectively.
This system has worked remarkably well in many ways, but we have seen manufacturers engage in shenanigans to try to extend their monopoly power beyond the time that Congress intended, by using various tricks to block market access for generic and biosimilar versions of their products.
For example, some manufacturers try to block generic entry by using distribution restrictions on certain of their drugs as cover to refuse to sell copies of those same drugs to generic developers. The brand manufacturers know that generic developers need these copies to run tests required for regulatory approval, and so they engage in a sort of regulatory arbitrage to prevent their competitors from being able to satisfy federal approval requirements.
When manufacturers engage in these and other efforts to block patient access to competitive products, it is antithetical to our shared public health commitments, and ultimately it threatens to undermine our broader system for balancing innovation and competition. Without timely access to follow-on products, we risk the whole system falling apart.
I bring this up because I want to highlight another example of this sort of game-playing – communications by manufacturers of branded biologics to frighten patients and health care providers away from using biosimilars.
We’ve seen communications that appear designed to sow seeds of doubt by suggesting to patients and health care providers that biosimilars are less safe or less effective than their reference products, or that there may be clinically meaningful differences between a biosimilar and its reference product – when in fact a biosimilar cannot be licensed or marketed unless it has first been established that there are no clinically meaningful differences from the reference product.
Some of these communications may avoid making overtly false statements. But even materials without an overt false statement can be misleading, and thus violate provisions of the FD&C Act and regulations – such as by selectively deploying a series of statements which may be accurate when taken in isolation, and perhaps omitting other important information, such that the overall message is misleading.
We’ve seen this trick before. After the Hatch-Waxman Amendments passed in 1984, and American patients were starting to learn about and accept generic drugs, some manufacturers of branded drugs disseminated materials to disparage generic versions that were competing with their drugs.
For example, some brand companies disseminated materials that suggested that their products were superior to other therapeutically equivalent formulations. Or they stated or implied that generic versions of the product were less safe than the branded product. Or they otherwise implied that healthcare practitioners shouldn’t use approved generic products or attempted to scare patients off from using generic drugs by creating the misimpression that these drugs were less safe, or weren’t therapeutically equivalent, or were inadequate in other ways.
Some of the communications we’re seeing today about biosimilars are using the same old play from the same old playbook.
The good news is that patients have come to learn the value of generic drugs, and the adoption rate has been overwhelming. It’s been estimated that now – 35 years after the passage of Hatch-Waxman – generic drugs account for about 90% of all prescriptions dispensed in the United States.
I believe we’re also on a path to a more vibrant biosimilars market. At FDA, we’re working hard to make sure we get there.
Patient education is an important part of that. That’s why last month FDA launched new materials as part of an educational campaign to help patients better understand the basics about biosimilars, that these products are as safe and effective as their respective reference products, and that they may provide more treatment options, increase access to lifesaving medicines, and potentially lower health care costs through competition.
As for communications disseminated to disparage biosimilars by creating the misimpression that these products are unsafe, or ineffective, or are otherwise something to be afraid of, there’s more to come soon.
In the meantime, my message is simple: Cut the shenanigans.
In closing, I want to come back once more to the values I articulated earlier. We are all partners in a joint enterprise to advance the public health and improve patients’ lives. I look forward to continuing to work together in furtherance of our shared commitments.