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By John Dodge

May 15, 2003 | A veritable Renaissance man was sworn in as the 18th commissioner of the FDA on Nov. 14, 2002. In a job that sat unfilled for nearly two years, Mark B. McClellan, M.D., Ph.D., is trying to streamline the drug approval process and improve communication with the public. Responsibility for the increasing need to protect the country’s food supply and to defend the nation from the threat of chemical attack has landed in his lap. Then there’s running the agency itself. As part of the Department of Health and Human Services, the FDA has 9,000 employees (and two McClellans besides himself) in 167 U.S. cities. FDA inspectors visit 16,000 facilities a year as part of the agency’s oversight mission. President Bush has asked for a $1.4 billion budget in FY 2004 in addition to the $300 million the FDA collects in annual users’ fees. Among the biggest increases in spending are those that will go toward protecting food, security, and safety. 

The 39-year-old native of Austin, Texas, received a medical degree from Harvard-MIT Division of Health Sciences & Technology (HST) and a doctorate in economics from MIT. He has taught at Stanford University and advised Presidents Bush and Clinton on healthcare. Bio•IT World Executive Editor John Dodge (JD) and The Boston Globe Reporter Naomi Aoki (NA) interviewed him in Boston in March before he delivered a speech at his alma mater, HST. Hours earlier, bombs had started falling on Iraq.

JD: Did President Bush advise you to carry on as normal even though the war started yesterday? 

Guidance from on high was we are in a state of heightened alert and we need to pay particular attention to terrorist threats to the country at this time. Earlier this week, the Department of Homeland Security announced Operation Liberty Shield. We’ve got a major role in that in terms of additional steps to keep the food supply secure.

NA: What do you see as your chief challenges to making the FDA more effective?

From some early staff retreats I had with our senior leadership and a lot of discussions with experts inside and outside the agency, there are [several] areas where I want to make a mark. One is in the area of counterterrorism, both in the development of better medical countermeasures and in taking some new and much-needed steps to improve the security of our food supply. The FDA’s got to change the way it does business.

Another is reducing adverse events. We do a pretty good job of making sure the products we regulate don’t cause side effects when they’re used as directed. We have a good preapproval process for identifying safety risks. Yet there are still very common adverse events associated with the use of products in actual practice.

JD: When you got to the FDA in November, what kind of culture did you find? Is the perception that the FDA’s risk-averse culture has affected drug approvals reality?

That’s not exactly what I found. I mean, some of those facts are definitely true. There has been a decline in approvals and a decline in submissions to the agency. There has been an increase in the approval time, but it’s hard to tease out how much of that is the agency’s doing. What I do know is that there is a great willingness in the agency to try to find better ways for us to do our job efficiently and to make safe and effective products available as quickly and as inexpensively as possible. We’ve announced a whole series of initiatives since I’ve been there, including reforms in the manufacturing process and in our postmarket activities that all share that common goal of getting safe and effective treatments available more quickly at lower cost.

Have you set goals on how much you want to shorten the approvals process?

The average time for drug approval depends a lot on the quality of applications coming in. That’s something that will reflect both FDA and company activities. But there certainly are a lot of things we can do that would have the effect of reducing the time of approval. We are interested in more performance measures of our activities to help gauge whether we’re really achieving our goal of contributing to making the innovation process more efficient. One thing that we announced back in January, for example, is a quality systems approach to our product reviews. That will include more and more use of performance measures related to our review process.

How effective can in silico testing or trials be? Could you see it replacing some testing in humans or animals?

If the bio-markers involved can be demonstrated to have a strong predictive ability for longer-term outcomes, health impacts, quality-of-life and length-of-life impacts, then that can be part of our regulatory process. We are conducting some reviews of our regulatory standards in a number of areas and in a number of diseases. Cancer care is a prominent one where we are asking for expert input on [this]. If there are valid bio-markers, that’s something that we would definitely want to consider.

Does that mean you’re optimistic about in silico testing?

I’m hopeful. I also want us to make sure we’re improving our postmarket activities so that if we do make an approval of a product based on bio-markers or other kinds of proximate outcome markers, we will have a mechanism in place that will get good data on whether that marker is really panning out in practice.

Drug companies complain they’re not getting up-to-date information as well as clear and consistent guidelines from the FDA. Has that been a problem?

I think we can do more. One of the main goals of the new version of the Prescription Drug User Fee Act is to give us more resources and opportunities for early communication with companies. We are implementing some pilot programs to do that.  We’re also going to be developing more guidance for companies about the regulatory pathways, both for important diseases as well as for the many new types of products where the regulatory pathways have never been clearly defined. Those are, for instance, cell and gene therapy, novel drug delivery systems, and pharmacogenomics-based treatments. These are new types of innovations that the FDA just hasn’t had to deal with in the past.

Do you want to accelerate implementation of 21 CFR Part 11 on electronic submissions for clinical trials, or slow it down?

Well, [we don’t] want to slow it down, but to clarify how we’re going to be implementing it, we want electronic submission of records as soon as possible. We heard from our earlier initial guidance on Part 11 that many companies were worried that our requirements were overly burdensome without commensurate benefits in terms of making more useful electronic data available. Our announcement last month [to review Part 11 regulations] clarified exactly what we expect. I think it’ll make it much easier for companies to comply with regulations and submit the information that we want electronically.

How do the HIPAA security regulations affect the implementation of electronic submissions?

Companies definitely need to think about confidentiality concerns and about FDA’s reporting standards. Our action last month [aims to] make it easier to comply with our reporting standards so that companies can focus appropriately on protecting the confidentiality of the information they collect.

Is computer prescription order entry the complementary piece of drug safety to mandating bar codes?

In order to take advantage of a bar code, you’ve got to have a system that enables reading the bar code information. Electronic patient record and computerized prescription order entry would obviously help with that, too. Bar code standards create an added incentive for hospitals and other healthcare organizations to adopt these kinds of systems.

They hold so much potential relative to reducing medical errors and overall healthcare costs.

NA: Will you make the review [and adverse reporting] systems more open to the public?

We mainly need to focus on making sure we’re setting up regulations that encourage effective communication about how products should be used. Can people get the information they need on benefits and risks clearly and concisely? Can doctors get the information they need quickly about appropriate prescribing? Right now, there are not a whole lot of doctors that use the FDA-approved label all that extensively for their prescribing behavior. I want that to change.

Just to finish this off, on dietary supplements we’re taking a lot more aggressive enforcement actions on claims made by the supplements that are not supported by scientific evidence. We’ve seized a lot of products in recent weeks. We send out a lot of warning letters about unsubstantiated claims, and we’re really going to try to create a competitive marketplace that is based on competition and good science about what people’s choices can do for their health rather than unsubstantiated claims.

JD: You mention electronic medical records (EMRs). Don’t they sit at the heart of information-based medicine? What are you doing there to encourage physicians and healthcare providers to use EMRs instead of returning to paper so they can get around HIPAA?

We can increase the benefits of voluntarily adopting electronic records. Bar coding is an example of that. You adopt an electronic system now, and you will have a built-in, safe, firm quality check on making sure the right patient is getting the right medication. We’re also trying to provide more of our information in electronic form. We have started a project at the FDA called “Daily Med,” which is intended to be a daily update electronically to the physician’s label. We’re also undertaking [a project not started yet] with the National Library of Medicine to help process information so healthcare professional groups themselves could get daily information from us electronically about whatever new information ought to go on the label. Another advantage of electronic records is that they would be able to take advantage of these daily updates.

Explain how the FDA will secure the food supply.

We have models of so-called critical control points where there are opportunities for infections or infectious agents to be introduced. Now, we have to think about not only what can go wrong, but also where people deliberately try to make something go wrong. That requires a shift in our regulatory resources. Over the past year, we’ve completed a comprehensive, classified analysis of the biggest threats to the food supply and best opportunities to address them. We’re acting on that now. We’re in the process of implementing four new regulations this year on food security.

NA: How long do you think it will be before new vaccines for bioterrorist applications are available for the public?

Some of the highest-priority vaccines like smallpox are present in our national pharmaceutical stockpile, and that’s a result of this fast action by the FDA working closely with the companies to help make the products available. We have not seen the same kind of innovation in medical technologies for treating agents of terrorism as we’ve seen in the treatment of many conventional diseases. Heart disease care has been transformed by new drugs and devices in recent years. We haven’t seen that same kind of progress with respect to agents of terrorism.

That’s why the FDA’s been very closely involved with and very supportive of the president’s Project BioShield proposal. The new proposal that the president made in the State of the Union [address] would, among other things, provide new and much-needed financial rewards for product developers that deliver effective next-generation treatments for agents of terrorism. This will create the kind of market that doesn’t exist now.

If you give bioterror countermeasures a shot in the arm now, how long until you see results?

The products could show up within months to, at most, a year or two. We’ve already started identifying the most promising available treatments. These include safer vaccines for smallpox that don’t have the same degree of side effects and could be used in people with weakened immune systems. They include a potential, more effective vaccine for anthrax.

Could other products with national and defense security implications, such as blood substitutes for wound healing, fall under an expedited review system?

We are engaged in expedited reviews for military products like that. The definition for BioShield requires that the product not have a commercial application separate from terrorism. In other words, if there is a potential market, as there might be for blood substitutes for emergency rooms and treatment of injuries sustained here, then it would probably not qualify for this mechanism. That’s not to say we wouldn’t take steps to help speed the development of those treatments.

JD: What happens if a company starts bioterror product development, invests millions of dollars, and fails?

That’s an outcome that companies are used to. Most of the larger companies have a diverse portfolio of products, and some of them are going to succeed and some of them aren’t. There’s no sure thing in biomedical development. Some good ideas just don’t pan out. And that’s OK. That’s the way we’re used to doing business.

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