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  5. Panel 1 - Presentations by FDA, Prescription Drug User Fee Act Public Meeting November 14, 2005
  1. Prescription Drug User Fee Amendments

Panel 1 - Presentations by FDA, Prescription Drug User Fee Act Public Meeting November 14, 2005

Opening Remarks

DR. GOTTLIEB: Thank you very much. I just wanted to start with a brief overview of the legislative history of PDUFA. And then Dr. Woodcock was going to discuss the impact that PDUFA has had on the drug review program at FDA.

[Slide.]

Modern drug regulation, as you all know, started in 1962 with the passage of amendments to the Food, Drug and Cosmetic Act that, really for the first time, put in place a requirement that drugs had to prove that they were effective pre-market. Before that, requirements were just focused on safety. But for the first time, manufacturers and product developers needed to conduct clinical studies to prove the effectiveness of drugs.

[Slide.]

Heading into the 1970s, there began to be some discontent that there was what was being termed a "drug lag" in the United States. Probably the landmark evaluation of this was done by a University of Chicago economist by the name of Sam Peltzman, who did an economic study showing that drugs were being approved first in Europe and that, in his estimation, his analysis, the delay in the market to new drugs was the deleterious effect of the delay on the public health was outweighing any benefits that were being accrued through that delay.

This kind of analysis continued to build in the '70s, and really reached a peak in the '80s, with renewed emphasis on patient access issues, of getting drugs to patients more quickly, that heightened with the AIDS epidemic in the United States. And all of this discontent and this focus on review times culminated with the passage of the first Prescription Drug User Fee Act in 1992 which, for the first time, gave FDA new resources, based on user fees, for the review process.

[Slide.]

The primary focus of PDUFA I was on decreased review time, so the resources went to things like medical and scientific reviewers, and it was focused mostly on the pre-market review process, and getting resources for support personnel and field investigators to try to accelerate the pre-market review. The reauthorization in 1998, in PDUFA II, for the first time focused not just on review times, but development times. And so there was an emphasis on cycle times, and trying to build in resources for things that would enable shorter development time; so things like resources for more collaboration between industry and scientists and the FDA that could help improve the quality of applications that the received. So you saw things like that built into the second reauthorization, which I'll elaborate on in a moment.

[Slide.]

And then PDUFA III continued to build on that; put the Agency on a sound financial footing, and also continued to build on pilot programs and other mechanisms aimed at decreasing development times, and addressing issues of multiple-cycle reviews; issues where applications go through two or three cycles before the Agency is able to reach a final decision on their status, whether to approve them or not.

[Slide.]

One important point I just wanted to back up and make today is that user fees are not unique to the United States, although the United States, I think pioneered their use as a modern approach to funding a regulatory agency, they're now a mainstay in Europe, where the EMEA is funded in large measure by user fees paid by product developers. And the UK's drug authority is funded entirely through user fees.

[Slide.]

I said I'd get back to some of the goals that were built into the PDUFA legislation. Here you see a chart, a breakdown, of the growth in the goals that were incorporated into the PDUFA legislation through a goals letter that was signed with the Secretary of Health and Human Services. So the legislation itself didn't include these performance goals, but they were negotiated in a side agreement, in a goals letter.

And you can see the growth in the number of commitments aimed at trying to foster increased scientific collaboration between the reviewers and FDA and product developers, all aimed at trying to bring more clarity to the development process and improve the quality of the applications themselves.

[Slide.]

I included this picture--it's a picture, I think, of Steven Galson fixing FDA's mainframe computer.

[Laughter.]

Steven doesn't fix it anymore. This must be when Janet was in charge of the drug center, because Doug Throckmorton's in charge of fixing it now.

But I included this because one of the thing that came with PDUFA III--it actually was incorporated into PDUFA II, as well, but more so in PDUFA III--was a focus on IT as a big part of trying to enable a more streamlined, more clarity to the development process that FDA. And so for the first time, in PDUFA III you saw commitments built into the goals letter that were specifically aimed at trying to increase the IT infrastructure at FDA and="" also="" increase="" the="" use="" of="" information="" technology="" to="" try="" to="" accelerate="" the="" development="" process,="" bring="" more="" transparency="" and="" clarity="" to="">

[Slide.]

So this is a list of the various goals aimed at electronic applications, specifically, that were incorporated into PDUFA III. And so explicitly in PDUFA III, there was a commitment for a five-year plan to be developed, an IT plan, with specific milestones; and also commitments made to foster the development of electronic applications and electronic submissions to FDA which="" has="" progressed="" very="" well="" under="" the="" fda="">

[Slide.]

PDUFA III, more than anything else, put the agency on a sound financial footing, with revenue targets that increased for inflation from 2003, and also adjusters built in to take account of increasing burdens put on the FDA through the submission of additional applications. And Dr. Woodcock and others are going to talk more about these adjusters that were built into the PDUFA III legislation, how well they've correlated or not correlated with the increasing workload that the Agency's been confronted with, particularly with respect to all that increased collaboration that was built into the successive PDUFA agreements, PDUFA II and PDUFA III, and the increased amount of meetings and other things that the FDA does to help bring clarify to product developers.

[Slide.]

Just to close: why does PDUFA continue to be important? Well, there's no question that the user fees add additional resources to the Agency, and help the Agency deal with the backlog of applications that existed at the time of the original legislation. But even more so than the resources that the PDUFA legislation enabled for the review process itself, PDUFA has enabled a fundamental management transformation inside the agency that I think sometimes isn't as widely recognized as the resources that it enabled for the review process itself.

And, as Andy discussed, this kind of modernization to the process internally inside FDA is going to be critical, because the evaluation of the new technology that Andy discussed--Dr. Eschenbach discussed--may well be more resource intensive if we're going to make sure that these kinds of new products get to patients efficiently.

Thank you.

MS. HENDERSON: Thank you, Scott.

Dr. Woodcock?

DR. WOODCOCK: Thank you and good morning.

Scott's told you about the background of the program and some of the different legislative phases it's gone through. I'm going to talk about the operation of the Prescription Drug User Fee program, what it really means inside the agency. And then Dr. Galson and Dr. Goodman are going to fill in the details for their specific programs.

[Slide.]

Now, one of the things I think that is of great confusion to the public is: what do these user fees pay for? I'm not going to go through the fee structure, but as many of you may know, it's divided up. Only a third of the fees come from applications; the rest of them come from levies on the manufacturing plants that are in production, and the products that are out there. And this was simply to spread the load around, and not burden any particular innovator when an application was submitted.

[Slide.]

The Agency doesn't give these fees directly to any entities within the Agency, they're administered in a central way and simply used to supplement the overall budget. And FDA must keep track, however, of how these fees are contributing to the overall process.

In the statute they define something called the "process of review of new human drugs." And that "human drugs" covers drugs and biologics, and that process definition describes what, in fact, can be paid for by user fees; in other words, activities eligible for support from the fee program. So the Agency collects a centralized amount of money and then that is allocated to support these various activities. It isn't in any manner a fee gets paid in, and then the reviewers know about that. It's simply a support to the activities that go on at the FDA. And I'm going to explain this a little bit more.

Now, what activities are covered? What exactly is paid for or supported by these fees?

[Slide.]

Well, during the investigational phase of product development, in the process of review of new human drugs, the following activities are covered. And isn't a totally exhaustive list, but it's most of the important activities.

First of all, the FDA has to decided, when a compound is ready to go into people, whether or not the safety data that has been generated about the new compound, whether it's a gene therapy or a new molecular entity or a vaccine, or whatever it is, and whether the safeguards that have been put in place are adequate to put that compound into the first person, and to initiate human testing.

So this is obviously an extremely important function, and this is supported by user fees.

Secondly, as the investigational progresses, and more and more people are exposed at higher doses or whatever, the FDA sets standards for the safety evaluation at each stage of this development. So the FDA reviewers must specify what safety tests are going to be done on the patients--all the patients; how long they'll be followed, and so forth. And in many areas, as probably Jesse will tell you, this is extremely tricky; for example, in some of the newer areas such as gene therapy, how long should the people be followed, how should they be monitored? But in any new intervention, a lot of attention has to be paid to this.

[Slide.]

Thirdly, the FDA has to set the requirements for how the dose is arrived at. This is a very important aspect of development. It's important for safety and also for utility or usefulness of a drug or biological.

And, finally, the FDA has to set standards for how the trials are conducted; what the design of the trial is. What are the endpoints for any given indication? In other words, what defines success? How long do people have to be exposed? What do you measure about the people?

And all these activities, my point is, are covered by the user fee program. And you can see they're very essential to making sure that products are properly evaluated, and subjects are kept safe.

This isn't all.

[Slide.]

As Scott alluded to, during the investigational phase, the FDA scientists must interact and advise developers on their trials; for their specific trial; not the standards, but that specific set of trials they're doing; what kind of safety monitoring they're going to do in that specific time. Trial endpoints should be agreed to with the FDA.

In the past, during the drug lag times, one of the problems was that many volunteer subjects, patients and others, were exposed to trials that ultimately turned out not to be useful. Either the FDA would not accept them; they were poorly designed; or they had the wrong endpoints. This is basically not ethical. And therefore it is very important there be interaction between developers and the regulatory agencies to make sure the correct trials are done; trials that will yield the information that is desired, and that won't unnecessarily expose human subjects.

[Slide.]

Another important function that's covered by user fees is the need for the FDA to continually monitor the development of adverse event; side effects or other adverse events that occur in the clinical trials. And the FDA will place clinical holds on trials if some risk signal occurs in the trials, or require modification; for example, ask a firm not to study higher doses, continue accruing more patients at lower doses and so forth, to ensure maximal safety of the subjects.

This is quite different than the role of the IRB--just for your information. The FDA has the scientific expertise in development of those specific products, and therefore has a lot of wide-spanning knowledge about the development programs; what can happen, and what to do. This is really synergistic with the IRB function. People in the IRB are looking for the ethical protection of the subjects: make sure that informed consent is accurate and that people are safe. But these are complementary functions.

[Slide.]

In addition, the FDA oversees clinical research through its bioresearch monitoring program. The FDA inspects IRBs that oversee trials of regulated products, and we also set standards and policy for these IRBs in this realm.

We also inspect the conduct of the trials of regulated products, and we set standards for how those trials be conducted. And that's called the "good clinical practice standards." Those are internationally harmonized standards for trial conduct, record keeping and so on. This also is covered by user fees. This obviously is a very important activity.

[Slide.]

Now when an application--a marketing application--is submitted to the FDA, there's a whole other set of activities that are covered by user fees. The FDA must review how the product is manufactured, and what controls are put on the manufacturing, and what testing is done on the product to make sure that it can be manufactured reliably at high quality.

The FDA also sends people out to inspect the manufacturing facility. And the FDA also looks at the packaging, or how the product is going to be shipped, and make sure it's stable and all sorts of things there.

The reviewers must look at animal toxicology that probably will elucidate things that you won't have found in the clinical trials; for example reproductive toxicity. We don't really study pregnant women usually in trials, and therefore we're extrapolating our findings about reproductive toxicity from animal studies.

Same with carcinogenicity: those are long-term studies that are done in animals to make sure that products are not going to be causing cancer; something you wouldn't find in the clinical trial program usually.

[Slide.]

What gets most attention during this phase is the FDA reviewers have to review the clinical data, both all the safety data. In addition, the FDA has to review the product for mix-ups; to look at the name of the product and other aspects of the product that could lead to confusion and medical errors, and potential deaths when the product was out in the market. And the efficacy data.

And, finally, the FDA reviewers look at and negotiate with the company on what is said in the drug label, which is the standard for what is truthful about the drug.

[Slide.]

In addition, around an approval a number of other activities happen. These are also covered by use fees: holding public advisory committee meetings; evaluating risk-management plans. If there's an identified risk of a product, then it's very desirable to, instead of just waiting for something bad to happen, to have a plan in place to try and manage that risk. Agreement on Phase IV commitments, and then we have to review those Phase IV studies and the results. These are all covered by user fees.

[Slide.]

Now, that's the scope of the activities that are covered. And there are probably others that I haven't mentioned. There's certain product testing that goes on. There's other things that happen.

Now, we've heard from our stakeholders over the years many, many times: there is wide support for FDA carrying out each of these activities. That is not to say there are always some people who think FDA shouldn't do these things. But the vast number of people believe FDA should carry out each one of these activities and, in fact, most of our stakeholders call for us to do more in each one of these areas, depending on what they're concerned about and what they're interested in. They want us to do more drug safety. They want to improve the development process for unmet medical needs--as you heard from Dr. von Eschenbach. They want more oversight of clinical trials of medical products and so forth.

But each of these activities require adequate scientific staff, with appropriate IT and support staff.

[Slide.]

Now, what the user fee program did, by supporting these activities, is enable the FDA to increase the staffing and the bioinformatics, the information technology systems, for these processes. The blue bars here, starting in 1992 on your left, and going through 2004, the blue bars show the total number of people against these activities that I just talked to you about. And you can see there's been an increase from about maybe 1,300 in 1992, to a little over 2,500 now.

So, there has been significant increase in the number of scientific staff that FDA has been able to put against these activities. And there has been a concomitant increase in many of these activities, as you'll see later.

The pale yellow bars are the appropriated FTEs; in other words, the full-time-equivalents, or the number of people FDA has available fromappropriate dollars, to oversee these activities, conduct these activities. And you can see that that number has gone down from 1992 to 2004.

So today, FDA has somewhat fewer people to perform these activities that are funded by appropriated dollars than we did in '92.

The maroon bars show the growth in people that was provided by user fees starting in 1993. And you can see in 2004, the Agency had more staff provided by user fees against these activities than we had staff provided by appropriations.

By putting these two bars together, though, and getting the blue bar, we do have staff that cover each one of the activities I went over. However I know the programs by no means feel they have excess capacity.

[Slide.]

Now, what happened with this increase is fairly well known. With more staff and also better managed process, FDA was able to reduce the review times. And overall, priority in the yellow bars here, that's really against unmet medical needs, basically. And then the standard applications are in the gray bars, where there are alternatives out there already. You can see that the time for review of each of those came down during the course of the program. And so there is a significant increase in access to new drugs and biologics. And you're going to hear more about that, I think, from the folks here, the other folks.

But more staff and a better managed process have also resulted in better scrutiny by the agency of the applications, and better articulation of the standards. And this is very important.

Just for example, CDER issued a reviewer guidance on how to do a safety review about a year ago; how to go through the safety review, and how to prepare a report on the safety review. This is an 85-page document.

The current modern safety review is an extremely complex activity. And this is not only for the reviewers, but also explains in a way to the companies all the bases that need to be covered. The reviewers are not only asked to say what's in the application about safety, but what is missing; what hasn't been studied.

Review templates by various centers have been developed. A huge number of guidances have been issued by FDA that explain the standards for many important topis. And the review function has been progressively organized and reorganized to really hone it, to make it efficient.

[Slide.]

PDUFA has also provided value for industry. Because of the decrease in review time, there are big savings for the companies because of the shortened time to get on the market. And the meetings that are held during the user fee program to provide consultation from the FDA are highly valued by companies, as a recent MIT study showed.

[Slide.]

What are the current challenges for this program, however?

Number one is workload. As you'll hear probably from Dr. Galson and Dr. Goodman, one of the issues is the way the fee adjusters are structured really had to do with the number of applications coming in. But once the meetings program was established as part of the user fee program, the desire for meetings with the FDA in consultation has risen sharply. And this is not accounted for; this workload is not accounted for in the fee adjusters.

There are additional challenges for the FDA which we could get into in the discussion, if we wish. One, the IT infrastructure and bioinformatics support is still very challenging. Many people have raised issues about direct consumer advertising regulation; the oversight of clinical trials. Again, that is one of the activities covered under the PDUFA program. Again, as a clinical trial conduct changes, it's becoming very challenging. And then preparing for the impact of the new science, as new science starts to really come into the Agency as very innovative products are developed, these tend to be more labor intensive and also raise challenges.

So that's an overview, I think, of the program as it stands. And I thank you very much.

Oh, one more.

[Slide.]

The fees--now the total fee, similar to the user fee FTEs, currently user fees in 2004 began outpacing the appropriated dollars for the program. So it is not a majority user fee funded program.

Thanks.

MS. HENDERSON: Thank you, Dr. Woodcock.

And now, from the perspective of the Center for Drugs, Dr. Steven Galson.

DR. GALSON: Thank you very much, Debbie. And I'm happy to be here to talk to all of you. I'll try to make up for a little bit of our being behind schedule, and zip through these.

I'm going to talk about five issues.

[Slide.]

The first is a little bit more detail about the submission trends, and the data for the work coming in; the impact of that and PDUFA on the number of meetings that we have with sponsor companies; the result of all this being approval of more new lifesaving drugs; what we've been able to do in terms of increasing the expertise of our staff; and then a little bit on the very, very contentious issue of the connection of PDUFA with the safety of drugs on the market that I know you've all heard a lot about.

There are a lot of different ways to measure how much work is coming into the Agency and into the Drug Center. And these are three graphs that cover NDAs, efficacy supplements and manufacturing supplements. And you can see, in general--you're not meant to look at the fine points here--but over the entire period of PDUFA, there's been a gradual increase in the submission of these documents for review by our staff, with ups and downs. It's leveled off pretty much in PDUFA III, but you can see the large trend.

But that doesn't really tell the full story, particularly bout what's happened in PDUFA III. Dr. Woodcock touched on this already: and that is the fact that we've gotten a huge increase in the request for meetings, particularly under PDUFA III. You can see we're up almost to--we actually are up to 2,000 meetings a year in FY2005. That's a lot of meetings.

And, of course, that doesn't tell the full story either, because with each meeting that we hold with a sponsor company, our staff has to have at least one, or probably two, preparatory meetings to figure out what the approach is going to be.

And then after the meeting takes place, there have to be a series of meetings among the staff to figure out the actions that are going to be taken as a result of the meeting.

So this is really a huge uncompensated area of growth in work under PDUFA; being very positive for public health and for review and access to new products, but putting huge pressure on our staff and managers.

[Slide.]

Another way to look at this is the special protocol assessments that we do associated with the early phase of drug development; again, very positive for getting new products on the market, but creating a huge workload for our staff. We provide an assessment in writing within 45 days of getting these special protocol assessments into the Agency. And you can see the large growth in those, again putting pressure on the staff to do more. And these cover clinical pharm tox and all sorts of other areas, as well: stability.

[Slide.]

The result of all this, again on the positive side, is that the cycle time, the number of times applications go back and forth between the agencies and the companies, has gradually reduced throughout the duration of PDUFA. And this was, of course, one of the goals. We're down to, you can see, in FY'04 really close to one to a cycle to NDA approval. And this is, of course, a huge improvement over two.

And the result of all this is that lots of new products have come to market; very, very important for patients.

[Slide.]

There were 226 priority drugs that represent significant therapeutic advancements, including--and this is not a comprehensive list at all--59 cancer -related products, 144 products to treat infections of all kinds, 63 specifically for HIV and hepatitis viruses, and 73 cardiovascular drugs. So these really cover the gamut of the real pressing public health needs of American patients.

[Slide.]

And, again, just by way of example, not a comprehensive list at all--and I don't mean to insult any area that's being left out of this--touching on a few key cancer-related approvals, one from a few years ago: Gleevec, and then more recently for leukemia and lymphoma Arranon; drugs to respond to the counterterrorism threat, to treat people who have been exposed to radiation; Alzheimer's disease, a very, very difficult therapeutic area; again focusing on HIV in children; and a very, very important advance, Reyataz IV, enabling patients to take one-daily HIV treatment, instead of this huge cocktail of pills that have to be taken across the day in multiple different combinations; drugs to treat chronic problems like alcoholism; and, again, fairly recently, Bidil was approved to treat a specific sub-population in Black Americans who are particularly at risk for certain kinds of heart failure.

So many of these represent important incremental advances in therapies, very important to patients and physicians who spend their lives trying to improve outcomes.

[Slide.]

The result of the program has as well been to allow us to dramatically increase our scientific expertise. And this again doesn't cover all of the areas of our scientific expertise, but just a few. And I'll point to some of these numbers.

We've increased physicians by 40 percent; pharmacists by 47; general health sciences by 56 percent; toxicologists by 50 percent. And the pie chart covers some of the top five medical specialties. You can see: internal medicine, pediatrics, neurology have all grown substantially. And that's very, very important. That gives these applications the opportunity to be seen by more people, more people with a broad expertise across the board in medicine; very, very important to us doing a better job.

[Slide.]

There has been a lot of attention to safety investments, and safety improvements, and concern about the safety of our products. Some of this attention has caused us to go back and look very carefully at how much of our resources are spent on safety. And we've had to repeat this message over and over again: that safety is an important achievement and an important area of attention across the board in the Center for Drug Evaluation and Research and, I know, CBER as well. It's not just focused in one or even a couple offices. Across the board in CDER, we spend 50 percent of all of our resources on drug safety. And this touches every single one of our offices.

There's a lot of additional work, attention, investment, and research, and procedure that has to happen in the drug safety area. But we have managed to make improvements and increases in investment in drug safety under the PDUFA program. Particularly with the last round of PDUFA, we're able to spend some of the user fee funds on post-marketing surveillance. We hope to see that continue and maybe be expanded.

[Slide.]

We've been working on reorganizations of the Center for Drug Evaluation and Research to focus more attention and staff on drug safety areas, both process of reviewing the drugs and developing policies, with appropriated funding earmarks, and increased focus on PDUFA IV as I've talked about. And we've got $10 million new dollars in the FY'06 budget that we hope will actually result in an increase as the budget process rolls up to a finish, which is going to be very, very important.

So these changes have resulted in continued improvements in both pre- and post-market safety in products.

[Slide.]

But to really make important strides in drug safety--and we have to focus on this over and over again--we have to continue to keep our eyes on scientific investments; investments in ways of reviewing drugs, in ways of looking at data, and creating data that allows us to better predict the safety of products, and better identify safety problems that drugs run into after approval. Without that scientific improvement, it's going to be tough to really make important large-scale increases in the safety of products.

There has been some attention among academic and outside researchers on the effect of PDUFA on drug safety. You're going to hear about those in more detail today from some of the authors. Researchers both at Tufts and MIT have shown that there hasn't been any difference in drug withdrawals across the PDUFA program as compared to the pre-PDUFA area.

[Slide.]

So, in summary, we feel that the program has dramatically contributed to public health and improved drug review; the expertise of CDER staff; the processes in CDER have dramatically improved over the course of the program. We've made some advances in safety, but we need a lot more. And I think we can all agree with that.

And, lastly, again, we haven't seen any evidence of a relationship between these advances in speed and adverse impact on safety of the products that are approved.

Thanks.

MS. HENDERSON: Thank you, Steven.

And last, but certainly not least, from the Center for Biologics, Dr. Jesse Goodman.

DR. GOODMAN: Good morning. You're going to hear some recurrent Themes, and I'll try to zip through this quickly.

[Slide.]

But let me just say, as it says at the bottom here, when you look at the vision of our center, which is to improve public and individual health, including, where possible, globally; and truly not just assure products are safe and effective, but facilitate their development and access to them; and then strengthen us in terms of our expertise and abilities, PDUFA has provided essential support in those areas. And I think Janet's breakdown of the support that PDUFA has provided FDA is very illustrative.

I should mention that this is a process that has global impact, not just U.S. impact. It's increasingly an international industry and, for example, I just came back from a WHO meeting where, if you look at some of the promise of some of the products developed here, vaccines for Rhoda virus, vaccines for haemophilus, which have pretty much eliminated that form of meningitis in this country, the potential benefits of those all over the world is just incredible.

[Slide.]

This is just a little bit about our performance under PDUFA. And as Steve and Janet have said, it's not just the funds--and Scott also mentioned--it's also how we look at and manage the process, and putting energy into the effectiveness and efficiency of what we do.

And I think this shows you, going from '93 there on the left, to '97 here, the timeliness of meeting first actions within goal on PDUFA I, then PDUFA II, and most recently with PDUFA III. And you can see we've moved from an organization where there were these delays and lags, to one that is highly efficient in meeting what, for us, were very large and complex applications, I think is an efficient review process.

[Slide.]

Steven mentioned the meetings. These are extremely labor intensive. We find them very valuable, not just for companies, but also for our people to have an interactive, science-based process which leans much more to what I talk about as problem solving rather than just problem finding, which is what happens when a process is completely iterative.

[Slide.]

And here again you can see the improvements over time, PDUFA II, and the very high level of performance in meeting various meeting actions in PDUFA III.

[Slide.]

As you saw with the Center for Drugs, this has translated, I think, into a very development process. It doesn't mean there aren't challenges for development that remain for both the developers and the FDA, but I think you can see here the number of cycles has dramatically gone down for both standard and priority BLAs. And I think that's a very important accomplishment that indicates that a lot of this communication is working.

And I have to say that I find usually when problems occur they're about communication. So I think communication is a very good investment.

[Slide.]

You heard a bit about the number of meetings, and we see similar things. In addition to these PDUFA meetings and formal meetings, we also have a tremendous number of informal meetings, phone calls, that both result from those meetings, or take the place of them. And, again, I think that this is a form of communication that, as Steve said, it's not just these formal PDUFA meetings that we track that have grown, but all the communication and planning that occur around them. And I think everybody agrees this is valuable, but labor intensive.

[Slide.]

What are some of the results on this health level? This is just an example again, as Steve provided, of some of the recent important approvals. The first accelerated approval based on probably surrogate markers of a vaccine this year, bringing another influenza virus vaccine manufacturer into the United States; a new technology of conjugate meningococcal vaccine; new combination products for boosters in immunization in the country; a number of new immunoglobulin, so important in treating immunodeficient patients, whether congenital or acquired; products for Rhesus immunization; products for preparing us for bioterrorism, such as vaccinia immune globulin, very high profile products.

In addition, for many of our products, their use is broad, and they're assessed in different settings, and there are some important efficacy supplements for hepatitis A vaccines and coagulation factors.

[Slide.]

So, again, to summarize, PDUFA has been an important factor in supporting an expert and also efficiently managed review process at FDA, including CBER.

I think an extremely important feature is the intensive interactions with sponsors during product development. And I would also say the impact of this goes beyond the meetings. There's a cultural impact, I think, for both manufacturers, investigators and academia and the FDA.

I'd also like to say that for some the new technologies, as Janet mentioned and Dr. von Eschenbach mentioned, these interactions are particularly important. They enable us to share information with industry that can help them in the development process, and they also enable industry to keep us up to date.

They also point out areas where there are needs for guidance, which again can be very important when you're dealing with things like cell and gene therapy, where you're sort of blazing new pathways, but can also be quite important for existing products as they evolve.

And we think the result, in part, is earlier access to safe, effective and innovative products. And these are products, such as vaccines, and blood products, in our center, that are essential to both medical care and our public health system, and to our country's preparedness.

So, that's our summary of performance, and the role of PDUFA in our center.

So we'll look very much forward to your input today and in the coming months.

Thank you.

MS. HENDERSON: Thank you, Jesse. And thanks to our first panel.

Panel II - Presentations by Academic Research Groups 

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