FDA, Drug Development and Health Care Reform: A Panel Discussion

Current and former FDA officials and a former Big Pharma head of R&D discuss FDA and the relationship between a regulator and the industry it regulates when it comes to drug development.

Ramsey Baghdadi

The FDA Amendments Act, which followed the withdrawal of the COX-2 inhibitor Vioxx, is viewed as a watershed piece of legislation. At the FDA/CMS Summit, The RPM Report brought together a panel of industry and regulatory experts to discuss the impact of FDAAA, FDA's role in the drug development process, and core pieces of health care reform, including comparative effectiveness research.

The panel included Steve Galson, MD, Rachel Behrman, MD, and Robert Ruffalo, MD.

Dr. Behrman is Acting Associate Director for Medical Policy at FDA's Center for Drug Evaluation & Research. Behrman now leads CDER's medical policy programs and strategic initiatives related to prescription drug promotion and advertising, clinical trial design, human subject protection and good clinical practices.

Dr. Galson served as the nation's top public health physician between October 2007 to 2009 as Acting U.S. Surgeon General. Prior to that, Dr. Galson was director of CDER.

Dr. Ruffalo was former President of Research and Development at Wyeth Pharmaceuticals. Dr. Ruffalo played a major role in the discovery and development of a number of marketed products, including GlaxoSmithKline's congestive heart failure and hypertension drug Coreg.

Q: The RPM Report: What should FDA's role be in drug development? Is it just uniquely the regulator? Is it facilitator? Is it initiator?

Robert Ruffalo: I think FDA needs to be regulator, as much of a free market person as I am, I do believe our industry has to be regulated. It has to be strictly regulated. But I also believe that the role of the FDA should be as facilitator. And I've often found them acting in that role as well. So, I think that's an important function. Initiator? I don't know about that.

There's a downside to that in that as we work with the FDA, there are people on the outside who might think, "Well, gee, they're collaborating with us and, of course, they're in our hip pocket." And I've heard that statement. I've never seen that to be the case but I've heard that stated.

Steven Galson: I agree with Bob. The primary role, of course, is regulatory. And that has to be primary, but after that, I would essentially say all of the above or almost all of the above. I think the system of developing medical products, the system of evaluating them and monitoring them after approval would be more efficient if FDA was involved even more than they are now in a stronger way and that has to be balanced with the tension of the pressures on the staff and the pressures on the budget.

In the discovery or the initiation side, they're not going to do the initiation research, but I'd like to see FDA around the table when NIH is deciding what are the next billion dollars going to go to in pulmonary drug development. So, I'd like to see more discussion. And I've frequently felt when I was there that it would've been nice if we were involved in X and you can put in the X. Not as a major initiative, but sometimes around the table. But, again, that has to be balanced with the workload, which is tough.

Q: The RPM Report: Dr. Behrman, does the Critical Path Initiative at FDA count as the agency acting as initiator?

Rachel Behrman: In a way, I think it's semantics and I'm not sure I see the distinction. We obviously are a regulatory agency. That's our statutory authority. I was privileged to be part of the early years of HIV drug development where we were all of the above. And I think the critical path initiative is an extension of that. For example, we recently initiated a dual antiplatelet therapy trial. In that trial, we were the ones forming the coalition and helping the companies to get it off the ground. I think that, Bob, to a certain extent, you're right. There are those that say collaboration is a bad thing, but I think we've proven them wrong.

Tough Vs. Easier Drug Reviews

Q: The RPM Report: Dr. Galson, what constitutes a difficult drug review where a center director may have to step in versus something that is more clear cut?

Galson: Anybody's who's been in a senior executive kind of position would agree in concept, when things are going smoothly, you don't even hear about them. Of course, those are the really easy ones where they don't come to your attention. Where it gets more complicated and specifically got more complicated at FDA is when there are luckily fantastic interdisciplinary teams at FDA that work together. That's one of the strengths of the agency. And they don't always agree. And so, the toughest things for me, and I'm sure most managers there would agree, is when good people who work for you have disagreements around science or around balancing benefit and risk. And that was always the most challenging to have to choose between competing ideas.

Q: The RPM Report: Dr. Ruffalo, were you sometimes deep in the development process where you said, "this drug is going to be a tough FDA review?"

Ruffalo: We've had the whole spectrum. We've had reviews that were relatively easy, straightforward, where we did actually work as a team with the FDA, a real collaboration on an antibiotic, for example, that was approved on time, expedited review. It was great. And we've had the other extreme where the chemistry wasn't so good between the people interacting on our side and the FDA side. And it could be our fault, could be their fault or both. And some of those were more difficult.

And we often have an idea of what's going to be a tougher review than others. It's often obvious to us in the beginning just some areas are more difficult therapeutically than others. So, we usually have a feel for what's going to be a tougher review.

Q: The RPM Report: So you do have a feel for it?

Ruffalo: Usually, we do. I don't think I've been surprised too often on what turned out to be a difficult versus an easy review. But, still, we have to work through the difficult ones as well.

Drug Approval Trends

Q: The RPM Report: We've seen an increase in drug approvals year-over-year. Can we learn anything from an improvement in actual numbers of new molecular entities (NMEs) approved?

Behrman: Well, I have the advantage of being at the agency for over 20 years. And a little bit like hemlines: up, down, we're too fast, we're too slow, we're too tough, and we're too the opposite of tough. They're small numbers and small changes in small numbers are very difficult to interpret. And we certainly wouldn't want to make much of that if it was in an NDA.

I think the important thing is what is the pipeline in general looking at? And that really was and is what Critical Path is all about. How many pre-IND meetings are we having? How many INDs are we seeing? What do these products look like? How much end-of-Phase II material is coming in and so forth? Those are probably better indicators of the health of the pipeline of the industry in general. Just to put a plug in for the Clinical Trial Transformation Initiative, the whole idea is to modernize the clinical trial enterprise in this country so we're not trying to read the tea leaves when we say is it 29 versus 31 NMEs.

Galson: I was always frustrated with the over-interpretation of these numbers. It's just absurd. So, I don't know if I would use the exact words fantasy. But the communications lesson, though, is that since we know Wall Street and we know our 24-hour day media environment, people are going to talk about these numbers no matter what. The challenge is to take the opportunity of talking about them to talk about the important initiatives that are taking place such as Critical Path and modernizing clinical trials and really getting the world of drug development focused on what makes a difference. And that's making scientific advances in the regulatory process and in the development process.

FDA: More Conservative?

Q: The RPM Report: Has FDA changed? If so, have those changes hurt or helped drug development let's say over the last 10 years?

Ruffalo: I think some changes have helped a great deal and some have hurt. As Rachel pointed out, the ability and the willingness of the FDA to meet with us at earlier phases, earlier stages on a far more frequent basis has helped a great deal. And it really is impressive to see how much time they make available even when they were short-staffed. They spent a great deal of time meeting with us. That's helped a lot.

We have seen a change. I believe that they are more conservative now than perhaps 10 years ago. And I think there are reasons for that. I don't obviously think that's helped us. But there are other areas, as I pointed out, where the FDA has been a great help.

Galson: I agree with the concept that there are some things that have helped and some things that have probably hurt. But the concept around FDA becoming more conservative, I always step back and say is this really FDA? Or is this society? And of course, what the experts at FDA are doing, they're not in the work for their own personal edification. They're in there to do a job for the country. And of course, what they are doing reflects what's going on in the larger society.

And I think we have, as a society, become more risk averse in a whole range of areas. We all wear seatbelts, where we didn't wear seatbelts when I was growing up. Helmets for bikes, you can go on and on and on. The society pays more attention to risk than it used to. And I think, sure, FDA's reflected that. Hopefully, it hasn't gone farther than the standard, but of course, we all know there are lots of standards. There are people that have very different perceptions about benefit and risk. And how you find the right answer to that in a world where there are people with lots of views is a huge challenge for any risk regulating agency.

Behrman: Oh, without question [we've changed]. But I think that, picking up on Steve's societal point, when there are no satisfactory alternatives, a patient and their practitioner are going to be willing to take more risk. We learned that early. We codified that in our regulations in [accelerated approval]. When there are therapeutic choices, then we must be very careful to make sure that if there is something risky around the market, there's a good reason why that product is on the market.

And finally, we have to get a lot smarter about making sure we're giving the right therapy to the correct patient, because there's nothing riskier than giving someone a therapy that will have no chance of benefiting them.

The Critical Path Initiative: Right Idea, No Money

Q: The RPM Report: How was the Critical Path originally envisioned and compare that vision to where it is now and where you see it going?

Behrman: We announced it in 2004. It really emanated from a conversation between [former FDA Commissioner] Mark McClellan, who in addition to being a physician, we all know, is an economist. [CDER Director] Janet Woodcock asked why was there so much investment with so little return? And in 2004, we hypothesized it's because the science underpinning medical private development was moribund basically, certainly not attended to.

In 2006, we got a little smarter and we asked, what does that really mean? We talked about technical standards, regulatory standards and the actual sciences. By a year after that, I was more and more articulating that in terms of the initiative, what we were really learning was that siloed medical private development, not only the year of the blockbuster, but of siloing, it was over. If we don't share information and we don't partner, we're really not going to get to where we want to be. And I think that's the overall message.

I think the changes that you may see will happen over the next few years. It's just a fact that we have limited resources. We remain under-resourced, although we have more resources than we did. Perhaps a little bit more of a federated approach in the medical product centers themselves would help.

Ruffalo: I would add that's my biggest frustration with the Critical Path. I'm not sure it's been funded adequately. And so, it's moved very slowly. We, when I say we, the heads of R&D, we meet together as a group. And we were strongly supportive and still are of the Critical Path from the very beginning. And we had hoped it would move more rapidly.

And you're right; I think the sufficient resources have not been available to move it more rapidly. There were times where we would even want to offer some of our resources and industry. But of course, there are certain barriers to doing that. And so, we couldn't actually overcome that. Particularly, for example, information technology, we were willing to pay for certain systems at the agency. But at the end of the day, at the very last minute, we were unable to do that. And so, again, frustration is the pace.

Q: The RPM Report: From the outside, it has appeared that the Critical Path has been greatly underfunded compared with the importance that has been placed on the program by senior FDA officials. Why is FDA chronically underfunded?

Galson: I was there in the implementation of it in the department halls. This is the case for a lot of government regulatory agencies. And of course, the reason for it is that they're popular with some people and unpopular with other people. There's always a balance at any moment between people who are happy with FDA and all the regulatory agencies.

There are always some people who are unhappy. And to get anything through our Congress and our system of government requires a certain degree of consensus around priorities. It's much harder for the regulatory agencies to achieve that consensus than it is, for example, for an agency like NIH, where what they do is mostly make people happy by doling out money. And there are people that don't get the money. Of course, they're not happy. But there isn't a member of Congress who doesn't have some medical research.

Q: The RPM Report: So FDA should start giving away money?

Galson: Exactly. I think FDA's willing to do that, willing to have grab programs. But it's always been difficult because of the concern of some people out there that if you give a regulatory agency more money they'll do more of the thing that Person X doesn't like. And that's the fundamental problem.

On Critical Path, I really think this is a failure of imagination of Congress to not realize that programs like Critical Path can really make a big difference in achieving a higher level of happiness and a higher level of camaraderie and efficiency in the system. It's really unfortunate.

Ruffalo: I think there's another factor as well that as our user fees have gone up and we make up a bigger proportion of the FDA's budget, there's less pressure on members of Congress to actually fund the agency that they're supposed to fund. So, I'm not sure that that's actually the right path.

Behrman: I think there's one other point. What we deliver is very long-term. If you pave a road, people are going to notice very quickly. And we don't pave roads; the payback is far in the future. And it looks discretionary.

The Drug Safety Era

The RPM Report: Dr. Behrman, is FDA still in the drug safety era or has the agency passed that period? Was there ever a drug safety era?

Behrman: I think we've always been in the drug safety era. I remember being worried about drug safety in 1989.

I think other people view a sea change at FDA post- Vioxx. And actually, if you look at our history, I believe that the kind of inflection point you're talking about happened around 1998 when mibefradil and Duract were pulled off the market. They were pulled off the market not because they were not effective, not because we could not label them in such a way that if one followed the labeling, they would be safe, but because we had evidence that the labeling was not being followed. And there were safer alternatives. And that was a big change. And I think that was the big change.

Obviously, there have been changes since Vioxx, but I see them more in the debate over risk communication and the debate over availability of information and the continuing debate over how much risk we want to assume. But I think the change was much earlier. And in fact, the more savvy people in the industry were asking us in the late 90s, "Are we going to see larger safety databases?"

Q: The RPM Report: Dr. Galson, do you feel like industry did as much as they could across the board in 1998 or with Vioxx? Do you feel like FDA took too much of the brunt of all this public backlash and congressional backlash?

Galson: That's a great opportunity whenever anyone asks the question preceded by has someone done enough? The answer's always no. So, we can always do more on any side. I'm not that interested in going back and pointing fingers at behavior that took place in the past.

But the idea is that the whole drug development enterprise and the enterprise of patients that benefit from drugs really need to take responsibility with FDA for trying to communicate better about the inherent risk of every single medical product. If you don't have a product that has some risk, it's probably not going to work. And having the public and members of Congress and society as a whole understand that, I think each of the parties could have done more and should see it as a challenge to continue doing more into the future. This is a problem that's not going to go away. It's worldwide. And as we try to tackle more challenging clinical areas, it will come up over and over and over again. It's not something that's in the past and no longer a challenge. It's an open question still.

Ruffalo: The industry was criticized around that same timeframe. I do think things change around Vioxx, maybe before, but I saw it clearly I feel around the time of Vioxx. But the FDA took more of a battering than we did. And that actually bothered me a great deal and a number of my peers a great deal. We were used to being criticized. But it hurts us more when the FDA is being criticized from the outside by people who actually don't have the medical knowledge. Maybe some of the pressures, if there were and I believe there were, came from outside the FDA, not from within the FDA. And I believe that.

I think that the FDA's wanting to respond to societal pressure for increased safety is not necessarily a good thing. I'm not sure that society in general are experts on risk benefit. I think the FDA are the experts on risk benefit. And I'd like the boundaries set for risk benefit by the FDA and not be people who second-guess the FDA. That hurts us.

And I am very worried that we're approaching expectations for safety in some therapeutic areas that are simply unachievable. And I don't believe that's coming from inside the FDA, but I believe it came from outside. And that was the FDA's response. Not from the upper level of the FDA telling reviewers, "You need to be more conservative or less risk adverse." I think it was a natural phenomenon or a natural response to seeing some of their leaders being criticized, often in public, by maybe members of Congress or the media who weren't really qualified to criticize them on medical issues.

Q: The RPM Report: Can you better quantify risk benefit analysis by adding more objectivity? Can it be done and should it be done?

Behrman: There is work going on. At least the way I think about it is whether it's a tool to actually help in the decisions, so a decision analysis tool, or rather a communication of that decision tool. It could be very useful, because part of the problem we face, we have not been traditionally the world's greatest communicators. And that does not help anyone. And I think we're making a concerted effort to be better. And that would be perhaps one thing that would help.

Galson: Rachel and a large team of people at FDA spent many years on improvements to the drug label. And you all know how the drug labels look now and how they used to look 20 years ago. And that's just a sea-change. But there is a lot more that could be done I think with labeling of medical products to help consumers balance between benefit and risks. We've always said the label is focused on practitioners and it is. But we need a better way.

And it's really agreeing with Rachel that we need a better way to communicate about benefit and risk. We focused on this a little bit in an Institute of Medicine meeting a few years ago. And there were some very interesting work going on in academia about communications tools. And there is progress being made on that at FDA. And I'd like to see the work continue across the regulatory agencies and industry as well to try to make progress. We absolutely have to in that area.

Behrman: I think it's the fault of all of us. We have I think very good regulations on content and format. We're not following them.

We are to blame at FDA, as is industry, and it's really something we all need to concentrate more on, because if we were following the regulations, we would have much better labeling. In addition, if those that are not covered by the regulation voluntarily complied, we would have better information. That's going to become particularly critical. We've had public meetings on the consumer medical information piece. And there's been a lot of enthusiasm for a single leaflet. If indeed we do go there, if we have good professional labeling to work from, all our lives will be much easier.

Does FDA Care About Investors?

Q: The RPM Report: Do you ever worry about the perception that FDA carries a higher regulatory hurdle compared to other countries and that actually hurts investment in biotech startups or some of these new technologies?

Behrman: I think historically it's clear – if we are a black box or we are impenetrable, it will hurt innovation. And we are very conscious of that. I think we're less conscious of the investment side, which you're talking about, but the actual accessibility, clarity of our standards. We know what lack of clarity can do.

Galson: There is no question that that is a perception and an issue. And since I left the government, I've been talking to a lot of people in the financial community. There's no question. I heard from a venture capitalist out in California who's active in the medical device area. He said: "I'm never investing another penny of our fund in a medical device until there's more clarity out of FDA." Whether this is a reality or – whether this is accurate or not, it's a reality of the world.

And a slightly different angle on it, internationally we're in a global marketplace now. If the US is seen or is actually in a more conservative position than foreign regulators we will lose business. We will lose jobs. We will lose competitiveness. And that should be a concern. I think it is a concern for senior people at FDA. FDA has enhanced substantially the collaboration with regulators in other countries over the last decade so that there is a closer connection on standards.

Q: The RPM Report: Dr. Ruffalo, you were head of R&D at Wyeth, and you were making these R&D decisions that had implication 5-10 years down the road. How do risk-benefit decisions come together under that cycle? FDA has said in the past that the standards don't change.

Ruffalo: I think when the FDA says the standards don't change, I think maybe they mean the regulation hasn't changed. And I agree with that statement. But I do believe that requirements for approval of a new drug or a drug where there are competing agents are different than before, for example, 10 years ago or even five years ago. And I've seen it.

We happen to be one of the companies that had many NDAs at the FDA right after Vioxx. We had quite a few. And at that time, relatively few standard review NDAs were being approved on time. And the FDA may have good questions to ask, maybe have good reasons for it, but to get back to your initial question, our investors, our shareholders don't really care.

I remember most every day being hammered because we had a great number of NDAs, all of which subsequently got approved, but not on time. And timelines matter to investors.

And I don't believe that the FDA should approve drugs to please investors. I'm not suggesting that. And I don't think they do. In fact, they don't. But it is something that we have to consider in big pharma. And I think it's probably even more acute in smaller companies too.

Comparative Effectiveness: Making FDA "Irrelevant"?

Q: The RPM Report: Will comparative effectiveness help or hurt in the context of FDA regulation?

Ruffalo: I think if it's not done correctly to FDA standards, comparative efficacy research will hurt. And it is already hurting the industry. It will make the FDA almost irrelevant. We're already starting to see that. Here's my worry. An amount of money has been put aside, $1.1 billion. Only a part of that can be spent now. That's not going to buy very much research. As somebody who's paid the bills for large clinical trials for a long time, that's not a lot of money and it's going to go nowhere.

My worry is that you'll see many small 100, 200 patient studies, all under-powered, and the default will be equivalence. Of course, the branded drug will always lose in equivalence because of price. We're already seeing some of this happen already, not done by the FDA, but insurance companies when they see a study, the small study that shows comparability, under-powered to ever show anything but comparability, the default is we'll only pay for the generic.

That obviously hurts us. It doesn't give the real life answer. We can't defend ourselves against that, because we can only tell a physician what's in the label. So, we can't argue against a flood study. So, if these studies are going to be done, they have to be done to FDA standards so that not just risk makes it in the label, as currently happens, but that benefit can be put on the label.

To put benefit in a label requires two relatively large pivotal studies. And you're not going to get many of those for $1.1 billion dollars spread out over several years. And that's my worry. Labels will get progressively worse. It won't be a level playing field and there's no way for the industry to defend itself, because we can only state what's in the label.

Galson: I would say I'm worried about comparative effectiveness research. But let me point out some things. The first is that the trend to do this sort of study, regardless of quality, just the trend to get this kind of information, is not new. The insurance industry and others were doing these kind of studies before. And the attention suddenly on comparative effectiveness because of the [stimulus funding] and the earmark of the money really distracts from the fact that this has been underway for a while. The standards that are used for these studies I think are very, very important. So, on that point, I really agree.

Of course, FDA's not going to change its approval standards, because there's suddenly a study that shows one drug's better than the other by a different standard. I think we can be confident that that won't change what's happening at FDA. But it may change what happens out there in the payer world. But, again, that trend is happening because of national economic conditions and changes in the healthcare system and healthcare reimbursement system, independent of FDA. So it is something we should be very concerned about as a country. It's not specifically focused on FDA, though.

Ruffalo: I believe it makes FDA, to some extent, less relevant on what their experts are doing. And that's benefit and risk. And I think this is probably the next big issue to hurt the industry.

Behrman: I wouldn't think of it in terms of whether it hurts the industry or not. I think that we're the FDA, we're here to serve the public. So, what is in the public's best interest? And anyone who's been in a position of trying to decide between two therapies or personally take two therapies knows there can be some confusion. I don't think it has to do with a generic versus a brand, but rather the therapeutic confusion that exists in the community and where people are guessing.

What I worry about is, you're correct, $1.1 billion is not very much money. The Congress has very high expectations and I think very unrealistic, frankly, expectations of what can be bought for $1.1 billion. So, instead of having a national dialogue about, frankly, a national problem list, what are the top five things we have to address to understand how to use the therapies that are out there? We may, for that money, divvy it up in tiny, little aliquots and have increased confusion instead of increased clarity. But the industry can seize control [through collaborative studies].

Ruffalo: Even studies that we do in industry that are small probing studies of a couple hundred patients get released because they're required to be released now. And the studies were probably under-powered, because we do those kinds of studies just to get ideas for the next step. Now, they're taken as evidence that Drug A and Drug B are the same. We won't pay for the more expensive one. We've seen it happen [recently] with Vytorin and niacin. We're already seeing people respond to that study, which was on an end point that actually is not even recognized by the FDA. I think this is a bigger issue than most people think it is.

FDA's View of REMS

Q: The RPM Report: How do you think risk evaluation and mitigation strategies (REMS) have really affected the drug development process?

Galson: I think we need to knock people off the horse of thinking that REMS are something new, of course, FDA has approved drugs for a long time, including risk mitigation strategies, regardless of what they are called after approval. The fact that it got this new name isn't a fundamental change in the way FDA is regulating. These explicit plans are required more now than they used to be required before.

And that has made a change of the agency and the industry thinking a little bit more in advance. I think that's good. It's good to think how could this drug potentially get into trouble in the way that it's used down the road? That sort of advanced thinking, although none of us have crystal balls, it's good to do it to the extent that we can, whether the REMS themselves are the right model for this, whether in the end they're adding to safety. I think those are all things that will have to be answered by careful studies somewhere down the road. But it's not a new concept. And I think putting a little bit more definition and consistency around it was a good idea in general.

Behrman: It's not a new concept. Restricted distribution has been around since the late 1980s. So, I think the real question is or the real challenge is to ensure that any of these strategies that are developed, that it starts with labeling, are developed in a way that best serves the public. The comment was made in passing, "does it make us feel better?" If we get to the point where we're treating ourselves or the industry is treating themselves, then we failed. If we develop a strategy, however rigorous or less so that best serves the public, then we've done our job properly.

Ruffalo: Anything that restricts our ability to market our products, now let me put the business side of my job on the podium, hurts us very much. As clinical trials are taking longer and longer, involving more patients, more trials per NDA, our effective patent life at the end is shortened. And anything that delays our ability to recoup the investment by limiting exposure, for example, really hurts our model a great deal. And it's something that's very difficult to recover from. The investment is already sunk.

As we become almost zero-risk tolerant, the industry and patients can't ever win by getting new medicines, because we can never win a risk-only debate. I really do believe that this almost obsessive focus on drugs is not good for patients.

We never promised, nobody ever promised that drugs are risk-free. There's a reason you can't go and just buy them. There's a reason you have to make an appointment with a physician, that you have to be diagnosed, that the physician has to write you a prescription and you still can't buy the drug. You have to go to a pharmacist who's now educated for eight years in many places and then you can get the drug. There's a reason for all those safeguards. Drugs are dangerous.

And for whatever reason, maybe it's the industry's fault, but for whatever reason, and I'm sure there's several reasons, the expectation is drugs should be absolutely risk-free. They never will be risk free and there's always a benefit that has to outweigh that risk. And drugs are going to hurt people. And you just hope that over the entire population, you're basically producing much more benefit than risk.

FDA and CMS: "Good Working Relationship"

Q: The RPM Report: Do you work closely with CMS?

Behrman: We have a tremendously good working relationship with CMS. And we have a collaboration ongoing, which we call Safe Rx, which is one of our, if you will, Sentinel pilots. And it's been extremely useful and will be producing data. We do think differently and we have very different budgets as well. But there's a very close collaboration. And I think that will continue to grow.

At a Phase II meeting, or end-of-Phase II meeting certainly, a sponsor is welcome to bring [reimbursement experts] with them to an FDA meeting. We are not welcome to invite whomever we want. I think we have said we are blind to costs. We don't quite mean it that way. We're very conscious of the difficulties this nation is facing. But as you know, we think there are ways that are very closely aligned with our mission and our statutory authority to improve the system, ensure that resources are used efficiently and intelligently and thereby free up resources to answer other questions.

Follow-On Biologics: Is FDA Ready?

Q: The RPM Report: Is FDA dreading implementing an abbreviated pathway for follow-on biologics?

Behrman: No.

Q: The RPM Report: Can FDA handle these kinds of applications?

Behrman: Without question, we can handle the science. Without question, we can handle the applications.

Galson: They are handling them.

Behrman: Right. We know that in fact we've published several papers, but one that very specifically talks about what we've done in the past. The politics are what appear to be difficult. And the economics are what people are struggling with. The science is – well, the most important point that we make is that we believe duplicative testing is unethical, human or animal. And we don't want to see that. We are ready to make the scientific decisions. We are ready to implement a follow-on biologics program. It will not be cheap. These will not be easy applications. We want the Congress to be aware of that. But we are ready. And we think that we're the right agency to do it.

Q: The RPM Report: Was this ever something you worried about when you were at FDA Dr. Galson – follow-on biologics?

Galson: We worried about it. We, again, like so many statements that people try to be succinct they get to the point of being inaccurate. There are follow-on proteins on the market. FDA's been evaluating biologic products.

But the scientific issues that you have to go through are not two separate issues. You still have to examine the safety and effectiveness data for complex molecules. The agency knows how to do that. It's a different order of magnitude with some of the currently approved biologic program products. But of course it can be done. It's a matter of looking at the standards and trying to predict what we can tell industry they will have to do in terms of steps to move forward.