Hi, everybody. We're going to go ahead and get started. There's no department update today, so we'll go straight to medicine grand rounds. We have Dr. Doug Throckmorton with the FDA here with us today. 

He's the deputy director for regulatory programs. He got his MD from Nebraska Medical School, did his residency at Case Western, fellowship at Yale and, prior to going to the FDA in 1997, did basic science research and practiced medicine at the Medical College of Georgia in Augusta and also at the Augusta Veterans Hospital. He has the responsibility of overseeing the regulation, research, development, manufacturing, and marketing of prescription, over-the-counter, and generic drugs in the United States. And so today he'll talk to us a little bit about what the FDA does in the process of development and regulation. So join me in welcoming Dr. Throckmorton. 

[APPLAUSE] 

Thanks very much. While I'm walking up here, I need to tell you I know Dr. Rosner. I can tell you some things you may not know about him if we can talk later on. Mitch and I were at Medical College together '92 to '96, something like that. He's a very good cyclist, or at least he was back in the day. 

So thank you for inviting me-- fun to come down and talk to groups about the FDA. As was mentioned, I came to the FDA in '97. So I've been there for a considerable period of time. 

I'll show you where I am right now. But just by way of background, I came into an entry level position, a medical officer, so-called medical officer, as a physician coming from Georgia and spent my time on the cardiorenal, cardiovascular and renal drugs development. I've had the good fortune of drug directing that division. So I was responsible then for the oversight of all drug development, drug regulation, in that space for a few years before coming to my particular position. 

What I want to do today is convince this to work. 

[INAUDIBLE] 

Yeah. I have to get the other [INAUDIBLE]. 

Oh, OK. 

Yeah. Sorry about that. 

No worries. All right, good. 

[INAUDIBLE] yeah. 

Good. So listen, when I talk to people about what the FDA does, I really have two general goals in mind. First, I want to sort of pull the curtain back a little bit. When we take surveys of people and what they think they know about the FDA, the first thing people typically tell us is we're a black box. 

We're an unknown-- we don't really even-- they don't, people, have a context for understanding what the FDA is really about. I remember as a physician in practice pretty much thinking that. FDA was the place I'd go, I don't know, vaguely to get a dose to start a drug. You go to the PDR. 

I imagine the PDR had something to do with what the FDA did. But I really didn't know very much more about it at all. So I'd like to give you just a little bit of an overview of the kinds of things we do with a focus on the things in the Center for Drugs, because that is obviously my background. 

I also want to help show you some of the kinds of issues that we deal with, particularly around the work that the Center for Drugs does. As I do that, I'm doing it for a couple of reasons. One is to highlight the complexity of the issues that we face. I'm really uniquely fortunate to be able to work day to day with some of the most really complicated public health issues we face. Having that chance to do that, I'd like to share what we have to do, the kinds of things that we face. 

Second, I want you to think about the teams that are required to accomplish that work. I have a goal, obviously, in mind. I'm hoping that some of you are then interested in coming to the FDA, because it is a very interesting place, a very rewarding place from a public health perspective. And I'd like to share some of that work with you. 

So my overall message is just that, first, we know what we're about. The FDA has a mission that we take seriously, that we are successful at from my perspective. We are committed to doing the things that need to be done. We understand the process that's required to achieve those things. And the success that we meet, the success that we have to accomplish, is met with agility, dedication, and scientific expertise. 

So here's the black box. The Food and Drug Administration is separated by centers broken up by kinds of products-- drugs, foods, devices, veterinary products, tobacco. And if you come to us and you say, I want to ask you a question about some health care product, the first thing that we're going to ask you is what kind of product is it? 

Is it a drug? Is it a food? Is it a dietary supplement, which actually turns out to be a food of a particular kind? Is it a cosmetic? 

You would think that answer would be straightforward. I'll just simply say it is not, so that a food that contains a drug substance from an approved drug product is a drug. It turns out that it is not legal to place an approved drug into a food or a dietary supplement save for a handful of exceptions. 

And so if you see that food, it is, in fact, categorized for our purposes as a drug. Those categories are all found in statute. I'm not going to bother you with all of those statutory nuances. 

But first and foremost, we determine how to regulate a product by deciding what kind of product it is. Dual classification is common, so combination products that you guys are all familiar with. The drug-eluting stents and the antibiotic coated catheters and things are combination products. They have elements of both a drug and a device, for instance. And they are categorized and regulated separately. 

The Center for Drugs is, as I said, the place that I work, the place that I've worked for the last 22 years. I am the deputy center director. I'm sorry, I'm one of the three deputy center directors. 

And so the Center for Drug Evaluation has about 5,100 people in it of which around 550 people are medical physicians. We also have pharmacologists and toxicologists. We have one of the largest collections of statisticians in North America, basically. We have more statisticians on staff than most any other entity, because we have to, because of the statistical review that's so important to us. 

Chemists, I'll come back to chemists in a little bit. They play an incredibly important role for us in terms of manufacturing and making sure that products are manufactured to quality. All of us are headed by Dr. Janet Woodcock. She's been around since the early '90s in one form or the other and continues to help us as we do the work that we need to. 

We, in general, have three buckets of activities that we take on on a daily basis. And I'm going to break the rest of my talk down by these three buckets. So I just want to spend a little time talking about them. 

Drug development and review is the thing that you read about in the paper most commonly. That's a FDA today approved x. FDA today talks about the results of trial y. Drug development is the sexy side of what we do. That's what Dr. Meyer used to do is help bring new drugs to market, work them through investigations, do drug applications, put them into clinical trials, work with manufacturers to decide whether they're safe and effective for their labeled uses, and put them onto the market. 

Manufacturing is the science of creating a reliable and quality product. We are fortunate in the US that we basically assume this when we take a pill. When you take an anti-hypertensive, you assume that it's been made to high quality. 

Hold that thought. I'll come back to that in just a bit. Because when that assumption fails, people are sometimes surprised. So it's an important part of what we do. 

And then the third piece, and the third piece I'll talk about today, I'm calling consumer and patient safety we understand a lot about a drug when it comes on the market. As it's on the market, we continue to learn new information about it both in terms of its quality as well as its impact in, in particular, populations. We have to continually update the same formation about the safety of the products as they're on the market for consumers. 

We have a handful of tools that we can use to accomplish those three buckets. And as I talk about the three examples I'm going to focus on, you should be able to think about which of these activities, these tools, we were able to use to accomplish those activities. We have regulatory activities, product review, policy development, enforcement. These are standard things for any governmental agency. 

Fundamentally, they are grounded in science and the statutory framework. So we take what Congress does and, obviously, have to implement those directions that they've given us. In the case of the FDA, we've been around more than 100 years. So the statutory framework is both extensive and complex. But it's important for us to stay within the statutory framework. 

And then fundamentally and importantly, in the last decade it's become clear to us that we needed to do more outreach, more engagement, more understanding of the groups that were using the products that we were regulating. So we needed to start building partnerships with patient advocacy groups, communicate better the results of the activities that we're doing. And these are ongoing work that we're doing. But that piece is particularly interesting, especially when we have to communicate complicated medical issues, like the sartans that I'll talk about in just a moment. 

So let's start with drug development and review. As I said, this is the side of the FDA that people typically see. This is the drug approvals and the things like that. There are many opportunities in drug development. 

We are at a tremendous time in our developmental history, our scientific work to understand better the genetics of cancer. The scientific work to understand better the frameworks around schizophrenia and other mental health diseases are giving us unprecedented numbers of targets to turn into therapeutics. I've listed a few of them here of the challenges that we need to do to take those targets and put them into use in the hands of the American public. 

Combination products are the thing that you read about a great deal. I heard someone say, a drug plus a device equals the future. So it is combination products that are really, you know, a tremendous source of improved use of the drugs that we have used historically, whether it's putting it onto a catheter so that the catheter is less likely to cause an infection, or it's a drug-eluting stent which allows a smaller amount of drug to have a focused effect. Combination products are just essential to innovation in health care space. 

Biosimilar drug products, you can think of them in general terms to be generic drug products for biologics and proteins, a growth industry, a place that we understand there's a lot of interest. Many of you in the room are likely taking biologic products, antibodies of one kind or the other. We need to try to move those into the biosimilar spaces as quickly as we can. 

Genetically targeted treatments have revolutionized oncology. And if any of you have taken your oncology training, you know that this is moving us towards a world of organ agnostic cancer treatment, treatment focused on the specific cellular attributes of the cancer less than the site of the cancer where it was found. 

And then last, but not least, there is a great deal of interest in let's just say the uncommon sources of drug products. And here I include the cannabis-derived drug products. And I'm sure many of you have read about the large interest in products derived from cannabis. 

We have to be sure that we're providing all of the help we can to the sophisticated developer of novel products, as well as to the less sophisticated developer of novel products. We have to be the even playing field, if you will, providing information to bring those innovative products to market. This is an example of a sophisticated medical products developer. And this is a product that's come onto the market. 

Aripiprazole was approved combined with an adjustable tracker that allowed physicians and patients to monitor the use of that product in a population, to understand when the product was being used and taken as directed, which we hope would ultimately be able to improve adherence. So this is the sophisticated use of a drug and a device together to improve patient care. 

The other end of the spectrum, as I said, is the intense interest right now from people that are interested in developing drugs derived from plants. Now, there are sophisticated drug developers in this space. I will tell you there are other developers that are, I'll say, less aware of the regulatory paradigm. 

We have to make sure that we put them in touch with the right people. When these people call us, depending on their interest and their level of where they are, I'll be the one that picks up the call. Now, I'm going to send them to someone else, but we understand the importance of making sure that they know there is in fact a federal pathway to approval and development of products like this. 

And so we make available all of our resources, so that, ultimately at the end of the day, we hope we get some products. In this case, we hope we get some data. We hope we get some evidence of safety and effectiveness that we can use. 

There are a lot of challenges to sustaining this kind of innovation. And I'm not going to talk at length about them, except to say that we need to be very conscious of the need to sustain innovation. Innovation is a kind of a fragile thing. 

People are making choices about where to put their investments. They're trying to understand their next things to do. They want to help with the public health, but they need to make sure that there is a return. 

So we need to be able to continue to make it attractive for people to innovate in the health care space, especially around drugs. We know that the clinical trials paradigm is not working in the United States to the extent that it needs to. The average clinical investigator, I'm told, enrolls one patient in their career. 

OK, that's not a big number. We need to make it easier for people to enroll patients and easier for them to incorporate their patients into clinical trials. We need to understand better the natural history of the important diseases. 

We need to figure out what to do with real world evidence, another long conversation I'm not going to be able to talk about a great deal. But one part of my portfolio are the controlled substances-- opioids, marijuana, those kinds of things. Their patterns of use and abuse are colored not just by the pharmacology of the drug, but also by the social patterns, the things that people are doing to make choices about how they're going to use them. 

If we don't understand that real world use of those products, our regulation for them is less than it needs to be also. So we need to find a way to use real world evidence in that way to improve the use of products. We also need to use real world evidence in a way to expand the use of products, understand better new indications, understand better new populations. That's a focus of a lot of attention to us. It's a hard thing to do. 

We need to figure out how to support the interest in developing products for very small numbers of patients. Historically, we've thought about the anti-hypertensive paradigm-- 1,500 patients exposed for six months, a lot of preclinical work, a lot of clinical work developing, the pivotal trials, et cetera, et cetera. If you have a disease where 30 people in the world have it, a different kind of a paradigm needs to be put into place to develop those drugs. They need to be developed, no question. But the kinds of regulation, the kinds of review that we need to do to make that happen fundamentally is different than the way that I would do things if I was developing another anti-hypertensive. 

And then the last thing I'll just mention, we always have to be aware of process. And we always have to think very carefully about how an agency as large as the FDA is structured to make sure that we're doing the things we need to do. CDER is 5,100 people. That's a pretty big organization. We've got to continuously look back to see if we need to make some changes there. 

We do have things that we can do to affirmatively support innovation. We can develop tools. We can encourage collaboration. 

We can improve data standards and regulations for those data standards, make it clear how we're going to make use of a new quality standard, for instance, or how we're going to make use of a new outcome measure for patient reported outcome. And we can help build databases and things. But as these things get integrated into a particular product development, it's just terribly important for us to continue to look for new opportunities. 

The result of this innovation has been that we've been able to move products to market more quickly than we were able to do historically. Congress has given us some authorities-- again, I won't walk through these in detail-- basically allowing us to shorten the amount of time, bring new resources to bear on promising products to bring them to market more carefully, more quickly. With that work, many of the products that you read about in the newspaper today are coming to the market more quickly than they were able to historically. 

As a result, last year we did 59 novel drugs, new molecular entities or new therapeutic biologics, or how we classify things as novel. Over 1,000 generic drugs, we're not talking a lot about generics today, but generics is another place where there's intense public interest in them. Many of you take generic drugs. You know how much less expensive they are, for instance, than the usual innovator drug. We understand very well the importance of making sure that those developments continue. 

And then a few notable product approvals-- we approved the first product from a marijuana derived source, Cannabidiol for refractory seizures. We approved a whole new class of products for migraines. Everyone in this room knows someone with migraines. A new class of compounds being brought onto the market is an important accomplishment. 

We approved a new drug for smallpox under a variety of our regulatory authority called our Animal Rule, which allows us to use animal efficacy in place of human efficacy in places where we simply can't conduct human trials. And obviously, smallpox is an example of that place. So innovation is important. 

We have been innovating. And with that innovation has come success. We have been able to bring to market valuable products. We have to continue to dialogue with people to do better. We need to improve trial designs in the clinical trials network, as I said, and ultimately make sure that our organization is aligned to be as effective as possible. 

Now, let me move to drug quality and manufacturing. So I said before that we're lucky. And I'll say it again. 

We are lucky in the United States, because of the manufacturing quality that's brought to bear to not just drugs, but also devices, to all of the medical health care products that we consume every day. We have an assumption that the drug that we take, the pill that we take, will be the same today and next week and next time we refill our prescription. And if we go to, I don't know, whatever, Oregon and fill up prescription there, we have an assumption of consistency, reliability, and quality whenever we take medicines in the US. Those are not assumptions you could make in many other parts of the world. And it's because of the quality manufacturing standards that are in place for the manufacturers of the products that are available in the US. 

That's the good news. The challenge is sometimes those quality standards fail. Sometimes we learn things after marketing that are concerning. And I'm using valsartan as an example of a time where those manufacturing standards were in place. 

And in this case, in fact, the manufacturer was the one that identified these impurities. So this isn't a blaming thing, because, in fact, the manufacturers were on this. But instead it reinforcers for me the importance of the quality standard. And it reinforces the challenge to the FDA of how hard our work is to ensure the standards are met. 

So valsartan impurities, I was on valsartan when this impurity issue broke. A side chain reaction that occurred as a part of manufacturing led to the formation of these nice nitrosamine compounds that have potential genotoxic potential. You can read about the fallout from that. 

Well, you can read about it this morning. We put out an announcement about ranitidine, another product that's also been found to have these similar compounds in them. We've had to respond to this by making choices about what products are able to stay on the market and which products have to be recalled. And as this slide shows, 1,100 plus lots had to have been withdrawn through July. 

These drugs are important. They are important for a variety of different medical conditions, 60 million prescriptions sold in 2016. And as you can see, it's a wide variety of medicines, not all of them that contain these adducts. Not all of them that have this concern. So the good news is it only affected some of the class of ARBs, not all of them. 

So from an FDA perspective, you remember I wanted you to think about what we needed to do as an agency to respond to these kinds of public health challenges. First and foremost, we need to understand the problem better than we did. The manufacturer showed us the information. We need to understand it, put it in context, and understand how it happened and what we needed to do to prevent it in the future. 

From a drug shortage perspective, those 60 million prescriptions needed to be addressed. I supervised the drug shortage staff also. Their first thought was, OK, losartan's going into shortage. 

You know, what are we going to tell our community? What are we going to tell doctors to do when we don't yet even know exactly whether the other ARBs also have a similar challenge? 

We don't know exactly what risk to describe here and what alternatives to suggest to people to use. So communications became very important to us very quickly in trying to respond to this crisis. It turns out that the foundation of the source of these compounds was in a manufacturing change. 

And the manufacturer had made some changes to how their product was manufactured. And I don't know what these structures are either. But I wanted to highlight it, because it was a simple change in manufacturing, a well-intentioned change in manufacturing that led to these compounds potentially forming. 

And the manufacturer had made them for very reasonable reasons. No chemist I think on Earth would look and have been able to predict that the consequences of this were concerning. After the fact, we were able to look back and understand where it happened. 

They needed to make it a little more efficient. They were worried about another toxic byproduct, so they were, in fact, concerned about reducing the risks to the compound through manufacturing. And the consequences were obviously one that were unfortunate. 

But because of this, we had to then go back and determine whether other drugs that had made similar manufacturing changes also had similar risks, identified new classes of drugs, not anti-hypertensives that needed to be looked at . And we needed to give guidance to manufacturers about how to test for all of these adducts. If you remember, there are now seven of these molecules that we've identified that are potentially genotoxic, all potentially concerning. 

We needed to figure out how to test for them and what information to tell the manufacturers. As I mentioned earlier today, we announced more information about ranitidine. And I encourage you to go back and look at it. 

It's an example of what's come out of this initial observation around losartan. But it exemplifies the things that the agency has to do when we learn one problem. One aspect that we need to take into account is, what does it mean for all of the other drugs that we regulate? 

It also means that we have to put them in context. So nitrosamine compounds are everywhere. I didn't see any bacon in the sandwiches out there, but I did look for it. You know, grilled meats contain these same compounds also. 

So as we communicated the risks of this toxicity-- and it is unacceptable, and we do need to address it from a manufacturing perspective-- we had to place it into a larger context. I come from the Midwest. These things are in the well water. And so while we can mitigate this risk, we needed to make sure that people understood that in a larger context it was one of many sources of this particular concern. 

More recently, we've also been asked by Congress what to do about drug shortages. This is just an ongoing manufacturing issue, the work that we're doing. We believe that one way to address these manufacturing qualities, one way to reduce the chances of these kinds of toxicities, is to improve the approach to manufacturing, to make it more integrated, more quality, more continuous, and away from a product by product review and development. And that's something we're working to try to put into place. 

So now, let's talk about post-marketing safety. The third of those three buckets that, remember, I talked about is the things that the FDA does on our daily basis. Simply put, the FDA has to respond when safety happens, when crises happen, when public health is challenged. We have to be able to respond. 

Long list of things like that-- I'm not going to talk about any of them. You could add many others. The opioids crisis I am going to talk a little bit, because I think it does illustrate the work that we can do. 

The vaping issues are currently something that we're involved in. I meet regularly with the CDC. We're trying to sort out what the CDC and the FDA can do to get to the bottom of that, to understand what is a particularly devastating injury occurring in many cases in very young people. 

Drug shortages imperil all of us, imperil the work that you guys do administering medicines to patients when you have to find alternative perhaps not fully equal treatments, because you can't get access to a drug that was available last week or last month. Vincristine is an example that we've been struggling with recently where we had two manufacturers in a space, and then one of them left. And the one left could not meet the demands. And the result was loss of an oncology drug that is critical for pediatric tumor treatments. So shortages are a crisis in the truest sense of that word. 

And then as I mentioned-- the nitrosamine compound issues. Many other crises happen. And as they do, it's part of our role to respond to them. 

But let me talk to you about the opioids crisis. Because I think it illustrates the importance of not just what the FDA does, but also the work that we have to do with the industry, with physicians and the prescribers, and with other parts of the government agencies. So you're all familiar with the opioid crisis. 

I expect you've probably all seen this slide or some variant of it. It comes from the CDC, showing that there was a wave of overdoses associated with prescription drugs. That's the purple one, I guess. 

That now appears to be flattening somewhat, that there has been a more recent surge in the risks of overdose deaths associated both with heroin and with the fentanyls, the illicit fentanyls that are coming into the country. Bottom line, the opioids crisis continues to kill many, many thousands of people in the US every year. And it continues to be something all of the federal agencies are working to address. 

It's occurring even though prescriptions are falling. So you all are more judicious with your prescribing of opioids. To date, we're not able to assess exactly whether that's entirely good. 

What we're a little worried about is some of this is being borne on the backs of people with chronic pain. But a reduction in opioid use is encouraging. It will fall into somewhere around 150 million prescriptions a year, pretty considerable number of prescriptions still. 

And now, we're being faced with a potentially new epidemic of combined use of stimulants meth and cocaine with opioids, largely elicits, but sometimes prescription drugs as well. So now, we're being handed a new challenge. We're in the process of trying to figure out what we can do with this one. 

This one's particularly challenging. Medication assisted treatment for meth does not exist. Finding ways to help those individuals come away from their addiction is really challenging. 

I won't read this all. Basically, this just reinforces from my former commissioner that this is on the back of the FDA. We, like all federal agencies, are obligated to find a way to confront the opioids epidemic. 

But we do have to keep in mind that it occurs at the same time that we are facing a crisis of inadequate pain management. I'm not going to read all these numbers. Many, many millions of Americans have chronic pain of one variety or the other. 

And as you all know, I'm sure, access to appropriate pain management, which typically does not necessarily include drugs is not what it could be. Whether for insurance reasons or for other process associated reasons, people are not able to get access to the pain management that they could benefit from. So as we reduce access to pain medicines, we need to try to prevent that from impacting the lives of people that are in need of effective pain management. 

So FDA has a plan that we are executing against. Again, I am not going to walk through all of these things. Behind these things are many dozens of various activities. 

Suffice to say that we have a process, we have a group that's focused on identifying things to do for the opioids crisis working with other agencies and the like. I do want to highlight one small aspect to this. And it relates to the first part of it, which I view as primary prevention. 

If I want to keep you from becoming addicted to opioids, the most effective way to do that is to keep you from ever using opioids, obviously. And to do that from an FDA perspective, there are two ways we can intervene. We can, one, help support better prescribing, so that you're prescribing only the right amount of opioids when it's absolutely necessary. 

And then, two, can we help you get rid of them when they're no longer needed? I won't ask any of you if you have any opioids in your medicine cabinets, but I expect the answer would be yes you're holding on to that bike and just in case. You're holding onto your OxyContin that you've got after your hip surgery or something just in case you need it. 

Well, that just in case, you know, carries a potential cost. And we'd like to change that narrative. So one thing the FDA is thinking about is packaging. 

What we know is that those opioids, those unused opioids cause trouble. They get diverted. They get sold. They get stolen. 

And the result is accidental exposures. The result is intentional misuse and abuse. And to the extent that we can reduce the movement between those arrows, we think we can make a positive difference. 

We also know that we all are giving too many opioids out. When we prescribe after, in this case, surgical settings, but also in medical settings, too, when we look at the numbers of opioids that people are prescribed and we ask if they use all of them to relieve their pain, the short answer is no. Focus on the right-hand column, the red column at the far right. 

Left over tablets, every outpatient surgery we looked at there were excess opioids left over when patients got done taking them. Consequences, obviously, means those are sitting around in medicine cabinets. Those are sitting around where they can be diverted to inappropriate or unfortunate use. 

Recently, Congress has given us authority to basically restrict the size of packaging for opioids, the idea being to give a smaller quantity of opioids for particular reasons. The goal then would be that patients would still get the numbers of medicines they would use illuminated by the data I just showed you. But they wouldn't get more. 

A doctor wouldn't write for the 90 pills with six refills in an amber bottle. You'd write for the O-pack for your post-wisdom teeth extraction. And that would be three days starting with a non-steroidal. And the consequences would be fewer numbers of opioids would be left over in medicine cabinets, all to the good. 

We're also working to encourage people to take those opioids and get rid of them when they're no longer needed. This is changing human behavior. This is changing human culture. And it's a little bit harder to get to decide exactly how to do it. 

But we do know that women make most of the choices about health care in the home. So women are taking care of children and grandchildren and aging parents. And they're making the decisions formally or informally about where those opioids are in the home. We hope that by targeting that population, encouraging them, empowering them to make a safety-based choice to get rid of those medicines we'll be able to give them information that they can use to make a difference in the safety of their families. 

For what it's worth, we take in several hundred pounds of medicines at the FDA campus every year when we hold the drug take-backs also. That's a picture taken from one of the drug take-backs here recently. 

We can't always anticipate what's going to happen with drug safety issues. We don't always know when nitrosamine compounds are going to be identified in a manufacturing site and a company is going to call us up and say, we've got a problem. We can't always anticipate the next wave of addiction that the US is going to choose to embark on. 

So what we have to do is try to prepare to be ready when those things happen. Whether that means putting in place new processes or knowing where to turn to for help when that happens, we have to be agile, flexible, and well-trained. Well-trained is a really important part of this. 

We were able to respond as quickly as we did to losartan, because we knew as much as we did about the manufacturing science used to create those products. If we had had to recreate that, identify it, find experts, et cetera, we would have been slowed in that response. So having that scientific expertise, having those 530 physicians-- to use another example-- is critical for us as we're doing our public health response. 

We also are, like everywhere, focusing on IT, trying to understand the best ways to use that as a tool. It's not a solution. It's not the thing that's going to solve all of our problems. But it is one element of us being ready to do the work that we do as quickly as we can. 

I'm trying very hard to use it in a pharmacovigilance way for substances of abuse. Because I know we're going to find new things, bath salts, or cathinones or something like that. And we just need to be as ready as we can as quickly as we can. 

Last couple of slides I have is just to say, on top of all of this, there are other challenges that make the hard work that I just talked about just a little bit harder as the drug regulator I'd say. Many of them are going to be obvious. Many of them are things that you guys face in your day to day, too. 

But first, data are always incomplete. I have often here data are always incomplete. You never know everything that you want to at the time when you have to act. 

Often, you're unable to measure the impact of what you do. So in opioids, for instance, the FDA has done a few dozen things in the last decade. Deciding exactly what each one of them contributed, which ones worked and which ones didn't, on a background of many other actions that many agencies are taking is just difficult. It's hard to identify and hard to understand. 

And then third, data is coming in unprecedented ways and in unprecedented amounts. So social science data coming in in terabyte form that we're being asked to integrate and make decisions about is just fundamentally changing the decision making process that we're being asked to do. As I said before, we work within our authorities. 

There's a lot of legislative interest in what the agency does. We spend a lot of time talking to Congress about a bill that they're interested in passing trying to anticipate what the outcomes are going to be, what the unintended consequences of a word or a comma or a period here or there will be for long-term drug regulation. Honestly, a lot of times it's difficult for us to do it. 

And oftentimes, we miss. And then we understand only later when the lawyers come in to tell us what the words say that we see the consequences. And so it's just another source of challenge for us. 

A third challenge, and actually this is the challenge that I think we would all welcome as public health officials, is expectations. People expect us to get it right. The FDA has a reputation to uphold. 

We are seen as the gold standard. We are seen as the ones that are going to sort those safety issues out when they occur, like other federal agencies. I'm not singling us out. But the expectation is, when problems arise, we will find a way to identify a solution and put it into place. 

The public is demanding more than they ever have in terms of transparency and information and action and timeliness. They want the right answer. And they want it faster than they ever did before. Those things are often at odds with one another in a world where we don't have all the information we want. 

The public is also as polarized as ever, perhaps more polarized than ever. And reasonable people do disagree passionately about the right course that we should be taking, that any of you should be taking. Demonizing the alternative course is obviously an approach that some people take. 

It's limiting. It makes it harder to find the right way forward. And for us, trying to focus on the full data on all of the available options is really the only way that we're going to be able to find a way forward. 

And then I always like to remind people that single solutions-- silver bullets, if only you did this, the opioids crisis would be solved. I hear that a lot. Drug shortages would be solved if all you did was revoke the GPO antitrust statute. Two words in statute, and drug shortages would go away. 

H.L. Mencken said it really well. For every complex solution, there is an answer that is clear, simple, and wrong. And complex problems typically require complex solutions. 

But then last, critical issue, we understand we cannot wait. We have to be prepared to act in the face of incomplete information with less information, fewer options than we would like potentially in the interest of the public health. So I'm going to end my talk and hopefully answer some questions just by saying thank you. Thank you to Mitch for inviting me down here. 

This is a transformational time in what I do. My agency has gone through an enormous change since I was a medical officer sitting in a cubicle in the cardiorenal division in 1997. Expectations, resources, challenges are all changing. They are changing more quickly than ever. 

I'm proud to work at the FDA. I'm proud to do the things that we've done. I'm proud to talk about the things that we've accomplished without trying to minimize at all the challenges that we continue to face regarding the enormous scope of work, the broad range of critical activities, fundamentally just the exciting challenges that face me, that face my agency when we come to work, and the need to respond in a timely, equitable, and appropriate manner. 

I believe we are imaginative. We are willing to question our assumptions. And we understand the importance of collaborating with outside groups. 

I do hope any of you, as you're thinking of careers, will think about what the FDA has to offer. I am beyond pleased that I made that career choice. It has been a pleasure to work there. And I thank you for your attention. 

[APPLAUSE] 

We have time for a handful of questions. 

Hi, [INAUDIBLE] from general medicine. Thanks so much for the presentation. And thanks for the work the FDA does. I was curious. I didn't see as one of the barriers sort of industry influence on FDA decision making. I wonder if you might comment on that. 

Well, so industry is less a barrier than I think a question of motivations. I believe, having worked with the industry now for a long time, the people in industry genuinely want to make a-- they genuinely want to develop drugs that have a public health value. You know, that's an important part of what brings them to work in the day. 

They do have an obligation to their stockholders. They do have this obligation to meet their financial responsibilities. We don't have that same pressure. 

But I think it informs a lot of the interactions that we have with them. So, sure, there are industry partners that are more focused on the bottom line than I wish they were. But I think at the end of the day, the people are as interested as they can be within that limitation in public health and doing the right thing. 

Hi. Again, thank you for a wonderful presentation and your great work. I have a question about a controversial situation. It gets to the issue of motivations of the pharmaceutical industry. 

And that was the case of colchicine. For those who aren't familiar, colchicine has been available for probably centuries and clearly effective, clearly safe for gout. And then a pharmaceutical company did, I guess, randomized trials to prove its effectiveness, which we already knew, and then applied for approval and patented it. 

And it went from about $1 or $2 a month to $300 plus a month in the form of Colcrys. And I just want your perspective from the FDA about how that happened and what was the feeling at the FDA about that. And it seemed that the only winners there were the shareholders. 

So I'll reveal I am married to Armenian. And Armenians use colchicine for familial Mediterranean fever regularly. So I was hearing quite a lot about this and this issue on that side. 

The unapproved drugs group also reports to me. So I was seeing the other side. Fundamentally, the company was doing, in a sense, what Congress told them they could. What Congress has said is that when you take unapproved drug and you make it approved, you go to the trouble of creating a label, of doing a study, of doing the manufacturing quality, and improving the manufacturing of colchicine, I'll just say they did that, too. You'll have to trust me on that-- that they're going to be rewarded. 

Congress said, OK, you do all that work and you get the FDA to sign off on it, we're going to reward you by giving you what's called exclusivity. We're going to make it so that you are the only ones that can market for those indications in the United States. And it's for a certain period of time. And there's all sorts of stuff about that. But bottom line, it was a reward system that Congress set up. 

Now, almost all the time that reward system works fine. The lawyers fight about how long it is. It doesn't last too long. Ultimately, we get generic drugs or biosimilars, and everybody's happy. 

Sometimes-- and I would say this is probably an example of one of those times-- it doesn't work well. A company comes in. They take that bill that Congress passed, the thing that they're able to actually require us to do. 

We have an obligation in a sense. If somebody has followed that rule, we're obliged to follow through in terms of the marketplace. And they take advantage of it. And personally, I can only say I really wish that had happened differently than it did. 

But it is borne out of the structure that Congress has given us to try to reward innovation enough to get new products on the market, to get improved manufacturing, include labels and trials. I don't want to try to say that there are not examples of times when that's failed. 

Doug, can I ask you-- well, first of all, thanks so much for a great talk. Can I ask you two questions about drug shortages? So one, it seems that there are certain drugs in the US or worldwide that are mission critical. Normal saline is an example of that. 

What's the FDA's stance on only having a single manufacturer for some medications that are absolutely critical to what we do? Then the second part of my question is the cynic in me jumps to the conclusion that there's no better way to increase the price of a drug than to create a shortage. How does the FDA guard that that's not being done? 

So amen to the first one, I completely agree. Multiple manufacturers is critical to preventing any kind of a shortage. FDA can't require a manufacturer to make a product. 

That is they can choose to manufacturer any level or not. I think that makes sense, right? You wouldn't want it in the other way. 

But we also can't require a new product to come to market. So what we have to do is instead encourage. So we have a list of actions. Let's call you the second IV saline manufacturer. And you call me up, and you say, I'm thinking of submitting an application for the second IV saline. 

We have a whole range of incentives that we can and do bring to bear to make it more attractive for you-- faster review times, more help from the review staff more, more sort of inspectional help and things like that to try to speed you to market, honestly, to do everything that we can to give you an opportunity to get to market providing you get all of the data and things together. So we want multiple manufacturers, because we know that not all manufacturers end up marketing in the US. And we have to build in that redundancy. 

Some people have asked if we wanted to have the authority to require that kind of redundancy for a select group of products. The challenge is identifying that list of products and having it be the same from day to day, from year to year. Saline's easy. 

I don't know. Sodium bicarb for crash carts may be easy or something like that. Other products are a little bit harder for us. So right now, we're approaching it by trying to make it as attractive as possible to come to market. And we think that that's going to be an important way to help encourage additional products to be available to prevent those shortages. Remind me of your second. 

So the second is, how do you prevent against companies creating shortages to jack prices? [INAUDIBLE] for that. 

We don't have any direct role in that at all. So what price manufacturers charge for their products isn't something that we regulate. It isn't something actually that we're able to incorporate into our decision making at all. 

I do have an economic staff that follows, that kind of work very closely. So I do know when those things happen. If we believe there is evidence of collusion where more than one manufacturer's working together to jack up the price, we refer them to the FTC. So that is something that the FTC has authority over. 

People argue whether, in fact, drug economy is a fully capitalistic system. And they point to those kinds of things when they do. Our job is to bring as many products as possible to the market. And hopefully, that's going to help mitigate the concerns about shortages. 

Hi, I was wondering if there's any thought of evolution within the FDA in your dealing with the approval of biosimilars. And I'm thinking particularly of insulin. The biosimilar approval there is becoming much more of commonplace manufacturing. But it still takes a long time. 

Can you say what you mean by evolution? 

Well, so I know that the approval process for a biosimilar is much more extensive than for a generic. And so is there a thought now that biologics have become so much more common, that the biosimilars are going to evolve more towards the generic in their approval process? 

So I'm going to take issue with the first part of what you said. It's true, biosimilars do have a different pathway, statutory pathway. The requirements and things that are laid out there are more extensive and slightly different than the ones for generics. 

I wouldn't call it dramatically more. They are a different kind of data, immunogenicity and some things like that have been added on, because we think they're terribly important. But our focus was to try to make them as similar to the generics approach as possible. 

It wasn't possible for some scientific reasons or whatever. We really did have in mind a generics model as we thought about biosimilars for exactly the reason you're sort of intimating. We want to make it as easy as possible to bring these products onto the market, recognizing that biologics are fundamentally different than generics. 

And so bio equivalence isn't something that we're always able to rely on. But beyond that, we have a whole group devoted to nothing but biosimilars. I should probably get your name before I leave here. No, I-- it's something they look at a lot, understanding that growth in the biosimilars field is absolutely critical to drug pricing. It's absolutely critical to improved access to those products and things. It's a really big priority for us. Yeah. No, we get it. We've got to make that as efficient as we can. 

Just really quickly, or as quickly as it can be, any thoughts about how the role of the FDA may change in regulating medicinal substances that are not marketed as drugs? So I'm thinking specifically about supplements, things that are marketed as dietary supplements, but intended as medical treatment or that are given by health care providers who treat primarily with homeopathic substances or with naturally occurring substances and how the FDA is going to change in how they regulate those things? 

Well, when I started, I talked about we focused first and foremost on what are you. And deciding when you're a drug is based on what you claim the product does. So when I think of a dietary supplement, they're allowed to make a certain range of claims, so-called structure function claims, in terms of what they accomplish. 

They help support bone health and those kinds of things. They can't make claims that they treat, prevent, mitigate, diagnose diseases. That's in statute. Statute says, if you make those claims, you are a drug. Independent of form or anything else, it puts you into the drug class. That would be the place I would start with with whatever other kind of product. A food that makes a drug claim is a drug. And homeopathy is a separate, very complicated issue-- longer, longer history in terms of the kinds of things that they've used. And the use of those products and things. But at the end of the day, we begin with that claim structure in terms of deciding what our regulatory approaches are, including things particularly for drugs. 

Dr. Throckmorton, thank you so much for being here. 

Thank you. 

[APPLAUSE]