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Scott Gottlieb, MD - Pharmaceutical Compliance Congress

This text contains Dr. Gottlieb’s prepared remarks. It should be used with the understanding that some material may have been added or deleted during actual delivery.

Speech before
the Pharmaceutical Compliance Congress
"Improving The Pathway for Medical Innovation"
Washington, DC

Remarks by
Scott Gottlieb, MD

Deputy Commissioner for Medical and Scientific Affairs
Food and Drug Administration

November 9, 2005

Thank you for having me here today. I know most of the speakers here during these past two days have been lawyers. And you have been presented with a lot of timely information on the legal issues that are affecting drug development.

I want to give you my view as a physician -- a view from my own clinical practice and of how I see drug development affecting medicine.

My hospital is similar to any busy suburban hospital in any town in America, and like all of these institutions, the care that patients receive has been dramatically transformed by new devices, new diagnostic tests, and new medicines.

Take the way we treat patients with a heart attack. Fifteen years ago, when Rip Van Winkle went to sleep, the clot busting drugs known as 2B3A inhibitors or TpA were just hitting the market. Super-aspirins weren’t yet invented.

It’s hard to believe that not too long ago, say 25 years ago, when a patient rolled in with a heart attack, the best care they could expect was supportive care. There just wasn’t much you could do – short of surgery – to actually stop a heart attack in its progress.

Now, it’s been ingrained on every starting intern that "time is muscle." And the idea that you can sit idly be while a patient suffers a heart attack is almost as old fashioned as the notion that infections are treated heating blankets.

The drugs that revolutionized the urgent care of heart attacks, the clot busting drugs such as TpA or the 2B3A inhibitors, or even diagnostic tests such as troponin or drug eluting stents, are all the product of a revolution in biotechnology that started in the late 80s and is still maturing as a science and an industry.

These were products of new science -- not only new ways of discovering drugs and devices, but also new ways of manufacturing them.

It was at this leading edge of the drug development landscape where many of the biggest risks were being taken by scientists, and some of the biggest payoffs were eventually made on behalf of patients and the public health.

And it’s this leading edge of innovation and entrepreneurship that I want to talk about today.

Because it is here where much of the promise I believe still rests for ameliorating the diseases that too many people today are still suffering from.

And it is this end of the drug development landscape, with all its promise, where there is also an increasing amount of uncertainty.

Uncertainty about whether the science will be sufficient to fully develop many of these new kinds of drugs and therapies that people are designing in their labs.

Uncertainty about whether the regulatory authorities like FDA will be able to keep up with all of these innovations, and have the tools and methods to evaluate completely new kinds of therapies that result.

Uncertainty over what FDA should do with ambiguous results from currently available drug development procedures. This is one of the biggest obstacles at FDA during our review of new products.

Most of the current tests are empirical, meaning that they are trial and error. They are not designed to explore the underlying mechanistic explanation of why a drug works or why it doesn’t.

It’s therefore difficult to interpret these studies when the results are not clear.

Too often, a reasonable and conservative approach to ambiguous results is to require additional, more extensive, empirical testing, even though this empirical pathway still leaves many questions unanswered.

This delays new products without always getting at the underlying problem.

And most of all: Uncertainty about whether the patients who need these treatments the most will be able to afford them, or whether the process for developing drugs will have become so long and expensive that it will put new breakthroughs further out of the reach of people who need them.

These questions and uncertainties are too apparent today when it comes to developing better medical products.

With new evaluative tools and techniques, however, we can improve the way we assess and develop new medical products, and reduce a lot of these uncertainties.

We can make the process for turning a discovery made in the laboratory into a treatment that can be safely delivered to a patient much more predictable.

I want to tell you today what we are doing right now at FDA to make our own regulatory processes more predictable and transparent, and to improve the way we communicate information – especially to patients and doctors.

And what we are doing right now to address a lot of the uncertainty that I think threatens to get in the way of scientific and medical advances that are close at hand.

I want to talk about the steps we are taking at FDA to develop better science throughout or programs to make sure that we are as sophisticated as the medical products that we are increasingly challenged to evaluate.

At FDA we are working on a series of new policies that together constitute what we call a new and modern approach to regulation.

We have found that in too many areas of our own work -- whether it’s the way drugs are evaluated as they are manufactured or the way that they are tested in clinical trials -- the standards for doing these important tasks have not advanced much, if at all, over the last few decades or more.

Even though, during this same time, the science and the sophistication of the medicines themselves have evolved and advanced significantly along with the tools and the methods for discovering them in the laboratory, the tools for actually testing them, to make sure they are safe and effective, and for manufacturing them, have largely remained the same.

What we found is that in too many places, our own processes and requirements sometimes serve to impede scientific development when it came to embracing better tools and methods for developing drugs.

This was true whether it was the design of clinical trials, the kinds of markers used to measure progress or success, or the tools for making sure that new medicines were being manufactured to the right standards for purity and potency.

By setting a benchmark, FDA inadvertently established a floor and a ceiling for what product developers would do when it came to adapting new development methods. Let me briefly give you five examples of where this was so.

Even though sophisticated and sensitive assays were sometimes being used in preclinical development to help measure whether a new molecule would cause toxicity to the liver, FDA was still relying almost exclusively on data sponsors submitted from mouse and rat experiments.

Even though early biomarkers exist that may eventually be able to help predict which benign heart rhythm abnormalities caused by some medicines, a process called QT prolongation, might progress into very serious problems called Torsades, where the heart literally stops beating its normal beats.

Even though these biomarkers are beginning to get developed, FDA still relies almost entirely on a sometimes imprecise scientific method that measures the length of heart beats on electrocardiograms.

Even though the science of genomics enabled doctors and scientists to start using genetic markers as a way to predict who would respond better to certain medicines, or who would have a higher chance of suffering a side effect that could otherwise be avoided – a field of science you are all familiar with called pharmacogenomics.

Even though this science was maturing, FDA had no formal way of accepting this kind of information, and no clear pathway for when it would and would not become part of the drug review process.

And even though we know that plain film x-rays are often an imprecise measure of whether tumors are really shrinking in response to cancer treatments, we still weren’t able to effectively integrate better tools for measuring "tumor response" rates, such as FDG-PET Scans. These scans can actually look inside tumors and see if the cancer cells themselves are dying off, even if the organs that the tumors are lodged inside of never shrink back to their original size on a plain x-ray.

Problem was, a lack of standardization for new imaging methods like PET has complicated their use in medical product development. And research that would qualify new imaging techniques for particular uses in drug development to enable earlier and better measures of effectiveness were not getting done.

Well, I’m pleased to say that on each of these four areas, and many more, FDA is taking unprecedented steps to develop the science that will lead to better, faster, and less costly answers about the safety and effectiveness of new drugs, and without simply exposing many more patients to experimental medicines or requiring a lot of old fashioned techniques, like testing more drugs on animals.

We are doing it through working inside FDA and through new scientific collaborations aimed at developing fundamentally better and more advanced ways of asking and answering all of these important questions about safety and effectiveness of new medicines.

For example, we recently announced collaboration with Duke University that will be looking for better markers of that heart rhythm problem, QT prolongation.

We announced just last week our Liver Toxicology Biomarker Study, which will be conducted under a Cooperative Research and Development Agreement or CRADA between the FDA’s National Center for Toxicological Research (NCTR) and a start-up expert in this science.

This new initiative aims to discover signs of human liver toxicity in easier, and perhaps more accurate assay tools.

We issued a guidance document that spells out more clearly how companies can submit pharmacogenomics data to the FDA, and how it will be used to support clinical development. I’m pleased to announce that this pathway has been used more than 20 times.

And we’re going to be announcing soon a new collaboration that could help validate the use of PET scans as an endpoint in cancer clinical development. This could provide a faster and more reliable way of measuring when cancer drugs are working.

All of these scientific efforts are part of our much broader program inside FDA to adopt a modern approach to drug regulation.

This effort is encompassed by a policy we announced more than a year ago called our Critical Path Initiative, which is being led by the extraordinary energy and talents of Dr. Janet Woodcock, FDA’s Chief Operating Officer, and the dedicated staff that has been assisting her.

This is much more than a single policy or a set of science projects. It is a fundamentally new vision for how a regulatory agency can use advances in science to help accelerate medical advances.

We’ll soon be releasing our critical path opportunities list that identifies specific places where we believe that new scientific efforts, if pursued, will increase the efficiency, predictability, and productivity of the development of new medical products.

This opportunities list will include specific projects we want to undertake in the development of biomarkers, new clinical trial design, bioinformatics, manufacturing improvements, and in targeting resources to urgent public health needs and therapies for children and adolescents.

Better scientific approaches for developing drugs not only means that we’re going to have more opportunities to take advantage of the new technologies that are becoming a standard part of drug discovery such as genomics and proteomics.

It also means we’ll have more opportunities for early detection of potential safety problems with new drugs. And more opportunities to learn important things about the effectiveness of new medicines without having to wait many years or expose more and more patients to experimental medicines as part of clinical trials.

Our modern approach to regulation doesn’t just start and stop with the development process – with the way drugs are tested during the typical three phases of clinical trials.

We are also going to be updating and improving the way that we oversee clinical trials through a major new initiative that we presented to FDA’s Science Board last Friday.

And we have also begun a major initiative to update and improve the way we regulate manufacturing through our good manufacturing practices or GMP imitative and our Chemistry, Manufacturing and Controls reforms.

What we have learned is that we can manage risks better if we know more information about new products earlier in not only the development process, but also the process for manufacturing.

When it comes to manufacturing, right now, some companies have adopted a "Don’t Use-Don’t Tell"; policy — they don’t use new technologies that they know can help them do a better job, so that they won’t have to tell the FDA about them, and risk regulators taking a skeptical view of the new approaches.

It is a problem for the industry when companies are so reluctant to adopt better scientific approaches that alter production processes because of regulatory uncertainty that they instead stick to old technologies and processes that were undoubtedly obsolete, expensive, and inefficient and not guaranteeing the best result.

It’s not only that old manufacturing processes don’t allow for all the tools that would ensure safety and consistency. They also waste money, which ends up costing consumers.

MIT and Price Waterhouse Coopers conducted studies of manufacturing processes and determined that the total cost of the current manufacturing infrastructure exceeded that of research and development by two or threefold. Today, drug manufacturing costs account for nearly 25 percent of a drug’s cost.

At a time when too many people are literally being priced out of the benefits of lifesaving drugs, we cannot allow outmoded science and old regulatory standards to stand in the way of better technologies that can allow product developers to be doing a better job and at a lower cost.

To address these concerns, the FDA has outlined a plan — the CGMPs for the 21st Century Initiative.

Like the efforts we are undertaking to bring better science to the development part of drug creation, this plan sets the direction for modernization of pharmaceutical manufacturing regulation, ensuring that we all pursue a science-based approach and that we use new technologies that can help better maintain our focus on pharmaceutical quality issues.

The FDA’s newly-created Office of New Drug Quality Assessment is a big part of our own internal restructuring that will be addressing these problems and opportunities.

Among other new parts of this broad initiative and reorganization:

We will be hiring new engineers to improve manufacturing technologies.

And we will be updating the way drug companies submit manufacturing information to us as part of their New Drug Applications.

Modernizing manufacturing, and modernizing our regulation of these processes, ensures that we more efficiently create safer, smarter drugs, and we can save billions of consumer dollars in the process.

For too long, our own tools and our own processes inside FDA, and more importantly the methods that product developers used to bring their drugs through clinical development, were not invested with the same scientific progress as the molecules themselves.

The clinical development part of drug development, and the manufacturing part, did not keep pace with the laboratory part that led to the discovery of the underlying molecules.

That’s changing, and at FDA we are aggressively courting partnerships with other agencies such as NIH as well as private and academic institutions in order to instigate new scientific thinking when it comes to the tools and process of actually developing drugs.

Many people have said that the absence of these kinds of coordinated, collaborative plans to attack specific illnesses has been a major hurdle to developing better medical products.

Now, at FDA, we are aggressively pursuing better ways of turning molecules discovered in the laboratory into safe and effective medicines that can be reliably manufactured and given to patients with the full confidence that we are doing everything we can to quickly learn about benefits and risks.

Many of the new tools resulting from this effort will also provide healthcare professionals with better information to use in guiding more personal choices about how to use new medical products.

We don’t want to be an obstacle to new scientific discoveries, but to enable them, because it’s often in the most cutting edge science that the greatest medical advances are made on behalf of patients and the public health.

Thank You.