[House Hearing, 112 Congress] [From the U.S. Government Publishing Office] PDUFA V: MEDICAL INNOVATION, JOBS, AND PATIENTS ======================================================================= HEARING BEFORE THE SUBCOMMITTEE ON HEALTH OF THE COMMITTEE ON ENERGY AND COMMERCE HOUSE OF REPRESENTATIVES ONE HUNDRED TWELFTH CONGRESS FIRST SESSION __________ JULY 7, 2011 __________ Serial No. 112-70 Printed for the use of the Committee on Energy and Commerce energycommerce.house.gov U.S. GOVERNMENT PRINTING OFFICE 72-917 WASHINGTON : 2012 ----------------------------------------------------------------------- For sale by the Superintendent of Documents, U.S. Government Printing Office, http://bookstore.gpo.gov. For more information, contact the GPO Customer Contact Center, U.S. Government Printing Office. Phone 202�09512�091800, or 866�09512�091800 (toll-free). E-mail, [email protected]. COMMITTEE ON ENERGY AND COMMERCE FRED UPTON, Michigan Chairman JOE BARTON, Texas HENRY A. WAXMAN, California Chairman Emeritus Ranking Member CLIFF STEARNS, Florida JOHN D. DINGELL, Michigan ED WHITFIELD, Kentucky Chairman Emeritus JOHN SHIMKUS, Illinois EDWARD J. MARKEY, Massachusetts JOSEPH R. PITTS, Pennsylvania EDOLPHUS TOWNS, New York MARY BONO MACK, California FRANK PALLONE, Jr., New Jersey GREG WALDEN, Oregon BOBBY L. RUSH, Illinois LEE TERRY, Nebraska ANNA G. ESHOO, California MIKE ROGERS, Michigan ELIOT L. ENGEL, New York SUE WILKINS MYRICK, North Carolina GENE GREEN, Texas Vice Chair DIANA DeGETTE, Colorado JOHN SULLIVAN, Oklahoma LOIS CAPPS, California TIM MURPHY, Pennsylvania MICHAEL F. DOYLE, Pennsylvania MICHAEL C. BURGESS, Texas JANICE D. SCHAKOWSKY, Illinois MARSHA BLACKBURN, Tennessee CHARLES A. GONZALEZ, Texas BRIAN P. BILBRAY, California JAY INSLEE, Washington CHARLES F. BASS, New Hampshire TAMMY BALDWIN, Wisconsin PHIL GINGREY, Georgia MIKE ROSS, Arkansas STEVE SCALISE, Louisiana ANTHONY D. WEINER, New York ROBERT E. LATTA, Ohio JIM MATHESON, Utah CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina GREGG HARPER, Mississippi JOHN BARROW, Georgia LEONARD LANCE, New Jersey DORIS O. MATSUI, California BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin BRETT GUTHRIE, Kentucky Islands PETE OLSON, Texas DAVID B. McKINLEY, West Virginia CORY GARDNER, Colorado MIKE POMPEO, Kansas ADAM KINZINGER, Illinois H. MORGAN GRIFFITH, Virginia 7_____ Subcommittee on Health JOSEPH R. PITTS, Pennsylvania Chairman MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey Vice Chairman Ranking Member ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan JOHN SHIMKUS, Illinois EDOLPHUS TOWNS, New York MIKE ROGERS, Michigan ELIOT L. ENGEL, New York SUE WILKINS MYRICK, North Carolina LOIS CAPPS, California TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois MARSHA BLACKBURN, Tennessee CHARLES A. GONZALEZ, Texas PHIL GINGREY, Georgia TAMMY BALDWIN, Wisconsin ROBERT E. LATTA, Ohio MIKE ROSS, Arkansas CATHY McMORRIS RODGERS, Washington JIM MATHESON, Utah LEONARD LANCE, New Jersey HENRY A. WAXMAN, California (ex BILL CASSIDY, Louisiana officio) BRETT GUTHRIE, Kentucky JOE BARTON, Texas FRED UPTON, Michigan (ex officio) (ii) C O N T E N T S ---------- Page Hon. Joseph R. Pitts, a Representative in Congress from the Commonwealth of Pennsylvania, opening statement................ 1 Prepared statement........................................... 3 Hon. Michael C. Burgess, a Representative in Congress from the State of Texas, opening statement.............................. 4 Hon. Frank Pallone, Jr., a Representative in Congress from the State of New Jersey, opening statement......................... 4 Hon. John D. Dingell, a Representative in Congress from the State of Illinois, opening statement................................. 5 Hon. Fred Upton, a Representative in Congress from the State of Michigan, opening statement.................................... 6 Prepared statement........................................... 8 Hon. Phil Gingrey, a Representative in Congress from the State of Georgia, opening statement..................................... 10 Hon. Henry A. Waxman, a Representative in Congress from the State of California, opening statement............................... 10 Prepared statement........................................... 13 Witnesses Janet Woodcock, Director, Center for Drug Evaluation and Research, Food and Drug Administration......................... 16 Prepared statement........................................... 18 Answers to submitted questions............................... 154 Paul J. Hastings, President and Chief Executive Officer, OncoMed Pharmaceuticals, Inc........................................... 77 Prepared statement........................................... 80 Jonathan S. Leff, Managing Director, Warburg, Pincus LLC......... 93 Prepared statement........................................... 95 Marc Boutin, Executive Vice President and Chief Operating Officer, National Health Council............................... 110 Prepared statement........................................... 112 Ellen V. Sigal, Chair and Founder, Friends of Cancer Research.... 122 Prepared statement........................................... 124 Allan Coukell, Director of Medical Programs, Pew Health Group, The Pew Charitable Trusts...................................... 129 Prepared statement........................................... 131 Submitted Material Statement, dated July 7, 2011, of the American Hospital Association, submitted by Mr. Engel............................ 58 Letter, dated February 8, 2012, from Jeanne Ireland, Assistant Commissioner for Legislation, Food and Drug Administration, Department of Health and Human Services, to Mr. Dingell........ 150 PDUFA V: MEDICAL INNOVATION, JOBS, AND PATIENTS ---------- THURSDAY, JULY 7, 2011 House of Representatives, Subcommittee on Health, Committee on Energy and Commerce, Washington, DC. The subcommittee met, pursuant to call, at 10:00 a.m., in room 2123, Rayburn House Office Building, Hon. Joseph R. Pitts (chairman of the subcommittee) presiding. Present: Representatives Pitts, Burgess, Shimkus, Rogers, Myrick, Murphy, Blackburn, Gingrey, Latta, Lance, Cassidy, Guthrie, Upton (ex officio), Pallone, Dingell, Engel, Capps, Gonzalez, and Waxman (ex officio). Also present: Representatives Bilbray and Christensen. Staff present: Gary Andres, Staff Director; Clay Alspach, Counsel, Health; Howard Cohen, Chief Health Counsel; Ryan Long, Chief Counsel, Health; Alan Slobodin, Deputy Chief Counsel, Oversight; Jeff Mortier, Professional Staff Member; Andy Duberstein, Special Assistant to Chairman Upton; Debbee Keller, Press Secretary; Chris Sarley, Policy Coordinator, Environment and Economy; Heidi Stirrup, Health Policy Coordinator; Lyn Walker, Coordinator, Admin/Human Resources; Carly McWilliams, Legislative Clerk; Kirby Howard, Legislative Clerk; Rachel Sher, Minority Senior Counsel; Stephen Cha, Minority Senior Professional Staff Member; Alli Corr, Minority Policy Analyst; Karen Lightfoot, Minority Communications Director and Senior Policy Advisor; Eric Flamm, FDA Detailee; and Karen Nelson, Minority Deputy Committee Staff Director for Health. Mr. Pitts. The subcommittee will come to order. The Chair recognizes himself for 5 minutes for an opening statement. OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA The Prescription Drug User Fee Act, PDUFA, was first authorized by Congress in 1992 with the goal of expediting human drug applications through the Food and Drug Administration's approval process. Under the Act and in subsequent reauthorization, the drug industry pays user fees to FDA, and FDA commits to meet performance goals such as reviewing applications within a certain period of time. This construct was designed to give industry certainty and predictability, but also to speed new drugs and treatments to the public. Details of the agreement between FDA and industry will be published on September 1st of this year, and by January 15, 2012, FDA will send its final recommendations to Congress. The current PDUFA authorization expires September 30, 2012, and it is my intention to have the reauthorization legislation signed into law by June 30 of next year. PDUFA is too important to leave to the last minute. The drug industry employs thousands of people here in the United States, providing good jobs that we cannot afford to lose. The forthcoming study from Patel Memorial Institute has found that every job in the biopharmaceutical sector supports nearly six additional jobs in the greater economy. If PDUFA is not reauthorized, this study estimates that 130,000 to 260,000 jobs would be lost. Americans are the most innovative people on Earth. Given certainty, predictability and transparency in the approval process, venture capitalists will continue to fund new research and companies will continue to develop new and innovative drugs. What we have heard, however, is that certainty, predictability and transparency oftentimes do not characterize the FDA's approval process. Frustrating both the drug sponsors and the public who are waiting for treatments and cures to everyday maladies, chronic illnesses and terminal diseases. The American people expect and have a right to expect that the Federal Government is doing everything possible to ensure that drugs on the market are safe and effective. They also have a right to expect that applications for life-enhancing and lifesaving drugs are not languishing on a reviewer's desk at the FDA. It is my hope that the new agreement balances both of these considerations, and I look forward to hearing from FDA, the drug industry, patient advocates and researchers today on our panels. I yield the remainder of my time to Dr. Burgess. [The prepared statement of Mr. Pitts follows:] [GRAPHIC] [TIFF OMITTED] T2917.001 OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS Mr. Burgess. I thank the chairman for yielding. I am mindful of the fact that the last reauthorization was June of 2007, so it is a little over 4 years ago. At that time, I was concerned about some of the restrictions that this committee placed on the advisory panels that advise the FDA about the approval or non-approval of drugs and devices. One of my concerns was we didn't follow the Institute of Medicine guidelines that no more than 40 percent of the people who are on the advisory committees have an interest in the product under consideration, and it was the will of the committee over my objections that no one on these advisory panels should have any interest or perhaps even any knowledge of the drug or device being considered. I thought that was a serious and glaring oversight on the part of this committee, and I discussed it with then-Chairman Dingell extensively and offered amendments that were repeatedly voted down on party lines. But that is an oversight that I hope that this committee can now correct in this reauthorization period. It appears we saw it unfortunately on display with the Avastin advisory panel last week in that there, to the best of my reading of the makeup of that group, there was not a specialist who dealt with breast cancer patients on that advisory panel so that there was no one on that advisory panel who actually followed a patient who was on Avastin for their breast cancer. Now we are left to defend the decision from the advisory panel to the FDA about the removal of that drug. And we are in a difficult position with Avastin because some people are apparently dramatically helped. Other people, the help is not so great. But it is, I think, incumbent upon us to get that right. Other things that I think we need to do, we need to discuss the possibility of surrogate endpoints for studies within the FDA. Certainly that was useful in the early days of the AIDS research back in the 1980s. And the fact that we base everything upon survival statistics now and we are not looking at things like tumor burden or some other surrogate endpoint I think is a mistake on the part of our advisory panels. I thank the chairman for yielding the time and I yield back the balance of my time. Mr. Pitts. I thank the gentleman and recognize the ranking member of the subcommittee, Mr. Pallone, for 5 minutes for an opening statement. OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE IN CONGRESS FROM THE STATE OF NEW JERSEY Mr. Pallone. Thank you, Chairman Pitts, and I welcome today's hearing on this very important subject. Five years ago, this committee led the way in making grade strides in FDA policy and safety measures. In fact, some have said it was the most extensive overhaul of FDA policy and procedure in decades. What is important to note, however, is that this committee worked through the issues in a bipartisan manner, and I am proud of the consensus that we reached. That legislation was supported by members, consumer groups and industry stakeholders. Together we recognized the need for a strong and well-resourced FDA to complete its mission. In addition, we accepted the reality that FDA must have the ability to be well-versed on the best science in order to get the safest and most effective drugs to the marketplace. Now, in doing so I recognize that FDA must minimize the inappropriate burden it placing on the drug companies so that they do not stifle innovation. America's competitiveness depends on our ability to innovate and keep America number one, and as such I continue to believe that the government must be responsible for facilitating an environment where Americans can continue to innovate. This is the key to creating new thriving industries that will produce millions of good jobs here at home and a better future for the next generation. That said, we must not sacrifice safety and efficacy in exchange for innovation. PDUFA has been a true success and we must build on that success. We can't move backwards under the auspices of economic benefits. So, Mr. Chairman, I hope we can move in the same bipartisan spirit as we did in 2007. Even more so, I hope that we can produce consensus legislation free of conflict and contentious issues. I look forward to working with you and my colleagues on this committee as this process moves forward and I welcome today's hearing as a first step towards that goal. I wanted to yield 2 minutes to my good friend from Michigan, Chairman Dingell, but I still have another minute left, so let me say that I would like to close by commenting on the importance of the Drug Safety Enhancement Act. That is a bill that I coauthored with Mr. Dingell and Representatives Waxman and DeGette. High-profile risks associated with the globalized drug supply like the Heparin crisis of 2007 have put Americans' lives at risk and our bill would equip FDA with the authorities and resources this it needs to keep peace with an increasing international marketplace of products so that Americans can have confidence that drugs they rely on will help them get better and not make them more sick. So as we move forward, I will continue, Mr. Chairman, to make reference to the Drug Safety Enforcement Act and that bill because I do think it is important and also has a place during this PDUFA debate. I see the gentleman is here. I yield to Chairman Dingell. OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF MICHIGAN Mr. Dingell. Mr. Chairman, I thank the gentleman and I thank you for holding today's hearings. I ask unanimous consent to revise and extend my remarks because of the shortness of time here. I commend you for the hearing today with regard to the FDA amendments that we are discussing with regard to PDUFA. This is important. If everyone will recall, it has been accepted, it has been a tremendous success because of the cooperation between government and industry. However, we need to address more problems. Commonsense authorities, like mandatory recalls, subpoena power, ability to seize and destroy imported drugs and raw materials at the border, making delay or refusal for inspection a prohibited act, are now needed to ensure that Food and Drug has the capabilities to properly oversee safety of our drug supply. These are authorities that would be given FDA under H.R. 1483, the drug safety bill I introduced with my colleagues Mr. Waxman, Mr. Pallone and Mrs. DeGette. These are authorities that are desperately needed in order to address the safety of our American public. I would note that without them, imports of dangerous components and raw materials of pharmaceuticals, as in the case of Heparin, continue to threaten the well-being of our people. My colleagues will remember that in the last Congress, we passed a food safety bill, which gave many of these authorities to Food and Drug, and which was, in fact, supported by the industry. It passed out of this committee by a heavy majority. It also passed the House and the Senate by a very large majority, and it is now standing to help and protect the American people. I would hope that we would follow the example that we set last Congress when we worked together in a remarkably bipartisan fashion to see to it that we went well beyond just scratching the surface with regard to food safety and do a similar thing with regard to prescription pharmaceuticals and so move to protect the health, safety, life expectancy and to ensure that pharmaceuticals will not cause harm or death, particularly where it is from imported raw materials for the manufacture of finished products. I thank you, Mr. Chairman. I thank the gentleman from New Jersey. I yield back the balance of my time. Mr. Pitts. The chair thanks the gentleman and recognizes the full committee chairman, Mr. Upton, for 5 minutes. OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF MICHIGAN Mr. Upton. Thank you, Mr. Chairman. This is the first hearing of the 112th Congress on the reauthorization of Prescription Drug User Fee Act in the current state of medical innovation in America. I look forward to discussing FDA regs and how they effect innovation, job creation and the American patient's accession to life-improving drugs. Congress last reauthorized PDUFA in 2007 with the Food and Drug Administration Amendments Act. That law as we know expires in September of 12, 2012, which is why our work to reauthorize this law begins today. One area that the committee will examine is the lack of predictability and certainty at the FDA. These problems at FDA appear to be stifling American innovation, costing Americans jobs and obviously hurting American patients. Another area we will examine is the risk-benefit analysis used by FDA when approving drugs and whether the agency is striking the right balance on delicate issues. These are concerns that the FDA is failing to consider the views of patients who need access to lifesaving drugs, including those drugs that carry some risk. The committee will evaluate provisions of the Food and Drug Administration Act amendments, including those affecting advisory committees in the risk evaluation and mitigation strategies. The rigid unrealistic conflict of interest provision has prevented in my view the FDA and its advisory committees from utilizing some of science's best minds and left advisory committee slots unfilled. We have to look at the implementation of this provision as to whether it really has caused delays in the approval process. Our goal has to ensure America remains the leader in medical innovation. When the law works properly, the field creates new jobs and ensures American patients do have access to the best therapies available. I thank the chairman, and I yield the balance of my time to Dr. Gingrey. [The prepared statement of Mr. Upton follows:] [GRAPHIC] [TIFF OMITTED] T2917.002 [GRAPHIC] [TIFF OMITTED] T2917.003 OPENING STATEMENT OF HON. PHIL GINGREY, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF GEORGIA Mr. Gingrey. I thank the overall chairman for yielding to me. I believe the Prescription Drug User Fee Act reauthorization gives an opportunity to review the ways in which we can help improve the FDA approval process. In an age where our economy is fighting an international battle to remain the leader in medical innovation and the jobs that goes with those industries and patients in other countries have access to medical treatments that American patients do not, we need all hands on deck. No longer can we afford to sideline experts simply because of their ties to industry. One idea I believe that deserves consideration, Mr. Chairman, is drawing from the joint NIH-FDA Leadership Council. This council was created in 2010 to spearhead collaborative efforts to improve the FDA regulatory review process. This initiative is a good, proactive first step toward improving and modernizing the FDA. However, I believe if we are going to be truly successful in improving both the efficiency of the FDA as well as our understanding of how emerging technology can be used to improve regulatory review, other parties need to be at the table. Agencies like the CDC and Homeland Security, experts from the drug industry and academia, as well as patient advocates all need to be involved. A stakeholder group made up of various agencies, scientific leaders and business and academia and patient advocates can help support the FDA in its mission to advance regulatory science as well as other meaningful reforms and emerging public health issues. I look forward to working with Dr. Hamburg, the chairman and this committee on the issue. In addition, this committee has spent years studying the oncoming public health threat posed by antibiotic resistance. It is a threat to our patients, it is a threat to our troops, and in the hands of terrorists, our national security. My colleagues and I on this committee, four Republicans, three Democrats, have introduced H.R. 2182, the GAIN Act. If we are to have the drugs needed to fight the looming threat of drug resistant bacteria, our legislation is an important first step in that fight. I hope to see it considered by this committee, this Congress, the 112th. With that, Mr. Chairman, I thank the overall chairman for yielding to me and I yield back the remaining time. Mr. Pitts. The chair thanks the gentleman and at this time recognizes the ranking member of the full committee, Mr. Waxman, for 5 minutes for an opening statement. OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF CALIFORNIA Mr. Waxman. Thank you, Chairman Pitts, for holding this hearing today. I think we can all agree that it is critically important that there be a vibrant and flourishing innovation in the pharmaceutical industry. The medicines this industry has brought us have saved countless lives and improved the quality of life for people the world over. Unfortunately, by most accounts we are in the midst of a dramatic slowdown in drug development in the U.S. The reasons for the slowdown are complex and multifaceted. At a time when you would expect there to be a surge of innovation, for example, because there is an unprecedented number of drugs coming off patent, the opposite appears to be true. I hope our witnesses will help us understand what is causing this innovation deficit and what we can do to help our drug companies succeed. A rising chorus of voices have begun to assert the view that it is the FDA that is responsible for this downward trend. These critics claim that the FDA takes far longer to approve drugs than its counterparts in Europe. Some claim it takes the U.S. twice as long as Europe. Others claim it takes three times as long. These claims may sound convincing, but we have yet to see the data to support them. I am aware of only one peer review study comparing drug approval times in the United States and Europe, and it found the exact opposite. This study, which examined the approval of 35 new cancer drugs, was conducted by one of our witnesses today, the Friends of Cancer Research. It found that the FDA is actually approving these lifesaving therapies much faster than its European counterparts. Some view every decision FDA makes through the prism of whether it is good for the pharmaceutical industry. But that is not the right perspective. The question we should be asking is, what is the right decision for patients? It is in no one's interests to have a weak FDA. American consumers depend on FDA to verify the drugs we are taking are truly safe and effective. If Americans lose confidence in the FDA, they will lose confidence in the pharmaceutical industry as well. We should all be united in the goal of ensuring that we have a strong, well-resourced FDA that is armed with a full compliment of authorities to protect us from unsafe drugs and to assure that these drugs work. That is FDA's fundamental mission, and that is why I strongly oppose any legislative proposal that would prevent FDA from insisting on adequate data from clinical trials and force it to approve drugs on an incomplete record. These proposals would prove disastrous for the safety and efficacy of our drugs supplied. The title of this hearing suggests that our colleagues across the aisle believe that FDA's mission should encompass job creation. Democrats have been leading the charge for legislation to promote jobs and we have been bitterly disappointed by the failure of the House to pass pro-jobs legislation. But we should not be misled. I hope we would all agree that FDA should not take jobs into consideration when it is reviewing the safety and effectiveness of a new medicine. We want FDA to ensure that the drugs we take are safe and effective. Whether jobs will be created is simply not a part of that scientific public health equation. I do believe there are areas in which the agency's regulation of drugs could improve. For example, improvements in FDA's scientific capacities will enable FDA to identify early end-points that can predict whether a drug will be effective which can result in better design of clinical trials and faster approval of new drugs. Making these kinds of strides require we work from real data, not self-serving urban myths. We should require a significant influx of resources. It is ironic that at the same time they are complaining that FDA should do a better job, the Republicans in the House passed a budget and an appropriations bill that would gut FDA funding by over $500 million. I want to turn briefly to the fact that we have an increasing globalization of our drug supply. The world has changed from the time of the original Food, Drug and Cosmetic Act. Today, more than 80 percent of active pharmaceutical ingredients are manufactured abroad, with China and India comprising the largest sources. Just yesterday, The Wall Street Journal talked about poor regulatory oversight of Chinese pharmaceuticals. That is why it is important to look at the Drug Safety Enhancement Act, which will go a long way toward providing FDA with these much-needed resources. Mr. Chairman, our staff has reached out to your staff and Mr. Upton's as well requesting we engage in a bipartisan process to look at this bill and work toward incorporating whatever we can ultimately agree upon into the PDUFA package next year. I hope we can count on this opportunity to work together because it is in the public interest. Thank you very much, Mr. Chairman. [The prepared statement of Mr. Waxman follows:] [GRAPHIC] [TIFF OMITTED] T2917.004 [GRAPHIC] [TIFF OMITTED] T2917.005 [GRAPHIC] [TIFF OMITTED] T2917.006 Mr. Pitts. The chair thanks the gentleman. The chair thanks the members for their opening statements. Any other opening statements will be entered into the record. The chair thanks the witnesses for agreeing to appear before the committee today. Your written testimony will be made a part of the official record. We ask you summarize your opening statements in 5 minutes. We have two panels today. The first panel contains a single witness. Dr. Woodcock is the Director of the Center For Drug Evaluation and Research at the Food and Drug Administration. Welcome, Doctor. You may begin your testimony. STATEMENT OF JANET WOODCOCK, DIRECTOR, CENTER FOR DRUG EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION Ms. Woodcock. Thank you, Mr. Chairman and members of the subcommittee. I am Janet Woodcock, Director of the Center For Drug Evaluation and Research at FDA, and I would like to thank you for this opportunity to testify about the prescription drug user fee program, or PDUFA, as I am going to refer to it. Congress instituted this program because patients in the United States were not getting access to new medicines as quickly as people in other parts of the world. This problem is called the drug lag, and it became particularly severe in the 1980s. The chart we have brought, which you can see over there, shows that PDUFA really had an impact on this drug lag. In the 1980s, as you see, fewer than 10 percent of new medicines reached American patients first. They were available first in other parts of the world. PDUFA was started in 1992 and, as the data show, it quickly improved the availability of new medicines to the point now where we lead the world in introduction of new medicines. I am a rheumatologist. I am a doctor who treats autoimmune diseases and arthritis, and I can attest to the revolution of therapies that has occurred since the start of PDUFA. Diseases that were crippling now have effective treatments that allow patients to lead full lives. Recently, my seat mate on a plane showed me pictures of her wonderful gardens that she cared for herself. She told me that 10 years ago she was confined to a nursing home and it was only when she was started on a treatment, a new treatment for her autoimmune disease, that she was able to improve and is now active and well. This is the kind of treatments that we have seen coming out during the PDUFA period. So since the start of PDUFA, increasing numbers of new medicines were available first in the United States. Currently we lead all other countries in the introduction of new therapies. Every 5 years, PDUFA must be reauthorized, and each cycle of reauthorization has brought new enhancements to the program. Most recently, there has been a focus on improving drug safety monitoring and that was the focus of the last cycle. Successful innovations, such as our sentinel initiative, resulted from that safety focus. For this cycle of PDUFA renegotiation, Congress directed FDA to conduct a very open and inclusive process with significant stakeholder participation. We have done so, as detailed in my written testimony, and I believe the outcomes of the negotiation have really been improved as a result of this new process. Now, the drug development enterprise is in a very different place than previous PDUFA negotiation cycles. Drug development faces many of the problems other industries do right now due to the economic turn-down. But more significantly, there is a severe productivity problem worldwide in drug development in which an ever-increasing R&D investment is producing ever-fewer new drugs. This isn't just true in the U.S. It is true everywhere. It is no exaggeration to say that the industry is in crisis. At the same time, the scientific opportunities have never been greater. It is incredibly frustrating to see the explosion in biomedical knowledge and at the same time to watch the struggles and repeated failures of drug development programs that try to utilize this knowledge. Despite these serious problems, things may be looking up. This year to date, FDA has approved 20 new medicines, just one short of the total approved last year, and many of these medicines are game-changers for patients. We do see a rise in new development programs coming into the FDA as well. We have been moving through the process set down by Congress for this cycle of PDUFA negotiations and we have developed a set of recommendations that are laid out in my written testimony. These include new steps to incorporate scientific advances into regulation so we can do what we can for the problems that industry is facing; also providing for meaningful patient input into the standards of benefit and risk that FDA applies to these new products; to provide a more transparent and predictability review process for sponsors, and there is quite a bit in there for that; and to further enhance drug safety. In closing, I would say that in addition to these challenges, the pharmaceutical industry and FDA does face the challenges of globalization, which are ever-increasing and are well covered, and I am sure you are aware of, both in clinical trials being done all around the world and medicines being made all around the world. We still have to ensure the safety and effectiveness for our patients. We look forward to working with Congress on all these challenges. We feel that the success that is demonstrated of PDUFA can be extended and we can do the right things, both for the patients in this country and for the industry that brings them new medicines. [The prepared statement of Ms. Woodcock follows:] [GRAPHIC] [TIFF OMITTED] T2917.007 [GRAPHIC] [TIFF OMITTED] T2917.008 [GRAPHIC] [TIFF OMITTED] T2917.009 [GRAPHIC] [TIFF OMITTED] T2917.010 [GRAPHIC] [TIFF OMITTED] T2917.011 [GRAPHIC] [TIFF OMITTED] T2917.012 [GRAPHIC] [TIFF OMITTED] T2917.013 [GRAPHIC] [TIFF OMITTED] T2917.014 [GRAPHIC] [TIFF OMITTED] T2917.015 [GRAPHIC] [TIFF OMITTED] T2917.016 [GRAPHIC] [TIFF OMITTED] T2917.017 [GRAPHIC] [TIFF OMITTED] T2917.018 [GRAPHIC] [TIFF OMITTED] T2917.019 [GRAPHIC] [TIFF OMITTED] T2917.020 [GRAPHIC] [TIFF OMITTED] T2917.021 [GRAPHIC] [TIFF OMITTED] T2917.022 [GRAPHIC] [TIFF OMITTED] T2917.023 [GRAPHIC] [TIFF OMITTED] T2917.024 [GRAPHIC] [TIFF OMITTED] T2917.025 [GRAPHIC] [TIFF OMITTED] T2917.026 [GRAPHIC] [TIFF OMITTED] T2917.027 [GRAPHIC] [TIFF OMITTED] T2917.028 [GRAPHIC] [TIFF OMITTED] T2917.029 [GRAPHIC] [TIFF OMITTED] T2917.030 Mr. Pitts. Thank you. I will now begin the questioning and recognize myself for 5 minutes. Mr. Gingrey. Mr. Chairman, we cannot hear you. Your mic may not be working. Mr. Pitts. All right. I will hold it closer. According to reports from the California Health Care Institute, and Ernst & Young and testimony here today, FDA's regulatory uncertainty is stifling American job creation. To compound the problem, foreign countries like those of the EU, China and India, are proactively trying too take American jobs by making their regulatory systems more predictable and efficient and creating an ideal innovation climate for companies. Given the importance of these innovator companies to our country and our Nation's patients, these developments are disconcerting, to say the least. While foreign regulatory bodies are becoming more efficient, FDA appears to be going in the opposite direction. Is FDA, first of all, aware that these foreign countries are proactively trying to take American jobs? Ms. Woodcock. We are aware that both Europe, which has the Innovative Medicines Initiative, Singapore, China, many countries are looking to build a very strong R&D biomedical development industry in their countries. Absolutely. Mr. Pitts. The second question: What is FDA's role in creating a hospitable climate for American innovator companies so that they can create jobs and create new lifesaving therapies for patients here? Ms. Woodcock. Well, first of all, I would like to start with the facts, all right? That chart shows when the U.S. is the country that first launches a drug in our country, and you can see that is continuing to go up. So that is compared to all other countries worldwide. You will also hear testimony about a comparison to Europe. And we are not in competition with Europe, but you can see in the U.S., the drug approval process is faster and drugs reach patients more quickly than in Europe. That is simply one comparison. However, we, since 2004 when we put out what was called the Critical Path Report, have been working with industry to try to solve a lot of both the scientific and regulatory problems that impede innovation and keep drug development from proceeding smoothly. So we are very aware of this. It is a problem for us as well as for the industry. The people who work at the Center for Drugs and regulate new drugs are doctors, and they are rheumatologists and they are pulmonologists and they are cancer doctors and infectious disease doctors. They know their patients need additional therapies and they want to see them out there for the patients. So this drug development enterprise is important for everyone and it is important to get it right. Mr. Pitts. And what has the FDA done to forestall the attempts by the EU, China and India to take our jobs? Ms. Woodcock. FDA has a very predictable drug review process. In fact, our review process is the most predictable part of drug development. If you can get through all the clinical phases of drug development where you test it on people, the process that FDA uses is extremely predictable. And that is a result of the user fee program. Right now we have the highest rate ever of what we call first cycle approvals, which is if companies send in their application, they get it approved on the first try. And we have timelines for that and we meet our timelines of review. So we have a very predictable and open process, and companies usually come first to the United States with applications for their new drugs. Mr. Pitts. OK, another question. I have heard from many patients that they believe their interests are not taken into account during the FDA approval process. Patients, including those with life-threatening diseases, are willing to tolerate additional risk in order to try these new drugs that will hopefully save their lives. How does FDA take patients into account when reviewing new drugs and how does it account for patients and their willingness to tolerate additional risk? Ms. Woodcock. The patients are the most important part of this. It is really for patients that medicines are developed and that the FDA does the review process, and we fully understand that people facing more serious diseases are willing to take higher risks. For example, we have a drug for multiple sclerosis that causes sometimes a rare, very serious and often fatal brain disease, and that drug was briefly withdrawn from the market because of doing this. When we talked to the patients, they said we are willing to take this risk, because this drug really helps prevent the progression of multiple sclerosis. That drug is available now to patients because we understand that when you face such terrible diseases, you are willing to take risks. Mr. Pitts. My time has expired. I recognize the ranking member for 5 minutes for questions. Mr. Pallone. Thank you, Mr. Chairman. And Dr. Woodcock, some of my questions are along the same topic, if you will, as the chairman. I guess this really shows that we are being bipartisan today. Most of my colleagues have been told that FDA is responsible for what is claimed to be a significant slowdown in development and marketing of new and innovative pharmaceuticals. Whether that is true or not, that is what we are told. There is a statement in Mr. Leff's testimony, he is on the next panel, which sums up what I hear. He states, ``While many factors have contributed to the escalating cost, time, and risk of new drug development, a changing regulatory environment at the FDA is the most significant.'' He attributes this, in large part, to increasing public pressure on FDA to focus more on safety and lesson benefit in the wake of the emergence of safety problems associated with Vioxx in 2004. He further points to numbers showing that FDA approved an average of 36 new drugs and biologics per year from 1996 to 2004, but an average of only 21 per year from 2005 to 2010. My question is, how do you respond to these claims? Is it really true that there was a sudden dropoff in approvals right after 2004 and that approvals in the years immediately preceding 2004 were well over one and a half times as frequent as in the years immediately after 2004, and has FDA really become too risk averse and not focused enough on benefits such that maybe innovation is being blocked. Ms. Woodcock. Well, I appreciate these questions. As a physician, I will tell you, I think it is important, though, to establish the diagnosis before we move to treatment. So it is really important to understand the facts. The facts are, first of all, as we have already discussed, the FDA approves drugs and gets them on the market more regularly first than any other country in the world, all right? We are meeting all of our PDUFA goals for review times, so our review time is very prompt. We are approving more than two- thirds of critical new drugs, those important new drugs that will make a difference for patients, on the first round. After they are approved, we review them and then they get on to the market. And we have the highest rate historically in 20 years right now of these first round approvals. So FDA is moving promptly and is approving a high percentage of the drugs that are submitted to us. However, we can't approve drugs that don't come in the door. And this slowdown is worldwide. This is not a FDA phenomenon. The pharmaceutical industry is suffering a crisis and we are not seeing as many submissions to us, nor is the EU, nor are the other regulatory authorities around the world, and this scientific challenge I think is the major problem that we face. Mr. Pallone. You have already, in response to the chairman's question, mentioned Europe. I read a study published in the July issue of Health Affairs by Friends of Cancer Research, which found that FDA actually approves cancer drugs significantly more quickly than its counterpart in Europe. Now, that was just for cancer drugs. But how does FDA compare with Europe in approval times of other classes of drugs besides cancer drugs? Ms. Woodcock. This is true for all of the high priority drugs that are going to make a difference for patients. We don't have all the data in a tabular form that we can give you, but we have looked into this. For example, we just approved two drugs for hepatitis C-- treatment of hepatitis C. Hepatitis C has been poorly treated. The treatment has difficult side effects and it often leads to liver failure and need for liver transplant and even death. We have just approved two new drugs that have a high rate of what is called virological response or cure, so we expect that many more people will be able to be cured for hepatitis C. Those two drugs are not approved anywhere else in the world right now. Mr. Pallone. Let me just ask you, would you say FDA could make some improvements in terms of helping industry proceed through the regulator process, and more specifically, where do you think the major roadblocks are going from earliest research to drug approval? Where can more effective improvements be made to shorten the time between discovery and marketing? Ms. Woodcock. The scientific breakthroughs we are currently experiencing with targeted therapy or personalized medicine or whatever, and I don't have time to go into it here, are giving us new opportunities to have new development pathways. We have been giving very significant thought to that, and I think we will be coming forth with some new development pathways that can help speed these medicines along and get them to patients sooner. This doesn't involve FDA review, because if we get a really good product into FDA, we can review it and get it on the market really quickly. What people are alluding to is the development time takes a long time. So we have some ideas about how to improve drug development for these highly effective therapies and we will be starting some efforts on that. Mr. Pallone. Mr. Chairman, could I just ask, I don't know if she does have something that she could follow up with on that, but if I could ask through you if there is more information, you could send us in writing about those new trends, I would appreciate it. Ms. Woodcock. I would be happy to do so. Mr. Pitts. If you would provide that to the committee. The chair recognizes the vice chairman, Dr. Burgess, for 5 minutes of questions. Mr. Burgess. I thank the chairman for the recognition. Dr. Woodcock, thank you for being here again. Reference was made to the European Medicines Agency, that is, the FDA is actually more rapid. Now, would it be fair to say that the timeline is more predictable at the European medicines agency and the FDA? Ms. Woodcock. Our timelines are very predictable. Mr. Burgess. Does that include a timeline start to finish, or a timeline where you reset the clock because you have asked for new information or a different study to be done? Because this is the question that people come in with. I see people in my office literally every week with a drug or device who say that the FDA changes the rules of the game when we are deep into the process. I can't get any of them to come here and testify before this committee because they are frightened, quite frankly, of you and your agency. They are scared to speak up because they know that that could reset the clock once again. Is this a fair criticism that I am getting from people who have drugs and devices before your agency? Ms. Woodcock. As I said, we ought to start with the facts. The facts show that we are approving a very high percentage of priority drugs, an extremely high percentage on the first cycle. So that is a 6-month review, all right, generally speaking. And so that is a very predictable review. The second issue you are raising is do we change the standards? Sometimes as we learn about side effects of drugs as they are on the market and we gain more information, then we do need to ask companies that have additional drugs in that class or whatever to look for those side effects and study them before marketing. So that does happen sometimes. Mr. Burgess. It is not just sometimes. It seems like it happens all the time. Now, I have to be careful not to confuse drugs and devices, but let me talk about devices for just a moment. I met a physician out in West Texas who developed a method for conscious sedation that was much more safe than anything that he had used in his practice as an anesthesiologist. It came to him while he was watching his newborn son being circumcised. And while it turns out that this device would not help in newborn circumcision, there are many other clinical applications where it would be very efficacious. As he told me this story, he said, just to put it in context for you, I developed this as a consequence of my son being a newborn and undergoing this procedure. And he is going to college this weekend, we are packing the car up to take him to wherever, and the device is no closer to being approved than it was 17 years before. Now, this individual no longer had a financial interest. It was simply because it was his baby literally, his idea that he wanted to see come to fruition and help patients. He sold it to a large medical manufacturing entity. But this thing was still bogged down in the process, and it was months and years of FDA advisory panels and this sort of thing. Even when they got clean bills by the advisory panel, then for some reason, the FDA would overrule and send them back to the starting point. He is not alone. There are other device manufacturers in my office, again, literally every week, and probably because this hearing is being televised, I will hear from a lot more of them now. But can you address that? We talked about the devices that are being off-shored because the environment is more friendly in other locations. You admit that other countries are actively recruiting our innovators. Are you working on that? Ms. Woodcock. Certainly. The reason that drug companies are going offshore has to do with the cost of either manufacturing or the cost of doing clinical trials. They are still submitting drugs to the U.S., because we are a large market. And as you see, we get drugs on the market before any other country in the world most frequently. As far as---- Mr. Burgess. I am going to run out of time, so let me go back to what you were talking about initially where you said your time line, that you are good, you are meeting your performance goals. There is a study from the California Health Care Institute where they talk about the FDA not meeting its goals and that your times have slipped since the last PDUFA reauthorization in 2007. Can you address that for us? Ms. Woodcock. Certainly. In the year or so after the passage of the Amendments Act, we were given a very large assignment of work by Congress in the Amendments Act which had many, many activities that we had to do. We made that our priority and accomplished those activities that we were directed to do by Congress. During that time, our goals did slip slightly and we failed to meet some of our goals, although we still had a very high performance. That situation has been rectified and we are now meeting and exceeding our user fee goals again. Mr. Burgess. According to this study, you have slipped 28 percent. It is fair to say the Democrats' last reauthorization slowed you down. Let's hope this reauthorization doesn't perform similarly. Thank you, Mr. Chairman. I will yield back. Mr. Pitts. The chair thanks the question and recognizes the gentleman Mr. Gonzales for 5 minutes for questions. Mr. Gonzalez. Thank you very much, Mr. Chairman, and welcome, Doctor. Quickly following up on Dr. Burgess' question, it is very interesting, because I think there has been some comments that we are losing jobs and such and investment in the United States because pharmaceutical companies want to do things outside of the United States, and the reason for that is the slow, cumbersome regulatory system that the FDA presents. Your response was that is not necessarily true. If cost is cheaper in another country, whether it is manufacturing or research and development, that is where the investment may be made, and it is strictly more on finances than anything else, eventually that particular company, whatever it manufactures, whatever it presents for consideration, is still going to come through FDA, that is right, and the reason, and you cited it, is that this is an incredibly lucrative market for pharmaceuticals, the United States of America. Would you say that in the United States of America, maybe there is a greater profit margin for pharmaceuticals than in other countries? Ms. Woodcock. I am not really qualified to comment on that. I am a doctor, not an economist. Sorry. Mr. Gonzalez. Do you know of any literature that might support the proposition that because of the system that we have in the United States, we may well be paying more for a certain drug, the same drug that is available here in the United States as well as in other countries? Ms. Woodcock. Yes, I am certainly aware of that. Mr. Gonzalez. How is FDA approval viewed? And I guess you can congratulate yourself because I assume it is very favorable, how is FDA approval viewed worldwide in other markets in other countries? Ms. Woodcock. Well, FDA has generally been viewed as say one of the gold standards. We provide a scientific and technical and highly unbiased review, and we base it on the evidence. We are really the only place in the world that goes down to the patient level data, and we get that data in and review it. So we are confident when we make a decision that is based on the actual evidence that has been generated. Many countries in the world look to FDA, all of our standards, our standards for manufacturing, our standards for clinical trials and so forth. But we have made a lot of efforts to harmonize those internationally through various arrangements that have been made. Mr. Gonzalez. Let's just say that there was just total reciprocity and you could sell a drug that was manufactured and approved by another country, this is a make-believe world. In your position, of all the countries, which regulatory agency regarding drug approval would you depend on before you would prescribe that drug for a patient? I know you are from the FDA and this may be quite an obvious answer. But seriously, if you were a physician in another country, wouldn't it be FDA, the United States of America? Ms. Woodcock. Well, I certainly have spoken to many physicians and many regulators around the world, and our process is viewed as a very robust and excellent process that people look up to as a gold standard. Mr. Gonzalez. We want you to do things timely, we want you to do it efficiently for all the right reasons, but not at the cost of quality and safety. That is the only point I think all of us would agree on. How do other countries finance their regulatory--let's say their FDA, their equivalent of FDA? Ms. Woodcock. In Europe, there are user fees. It is not the same arrangement because the countries give scientific experts to the process and there are multiple countries involved in the EU. There are different arrangements around the world. Many of them involve user fees of one type or another. Many countries do not have the personnel, scientific personnel and resources, to mount a kind of review that we do, so they rely upon conclusions from the World Health Organization, from the FDA, and from others. Mr. Gonzalez. I guess my final question, I have 30 seconds, and that is, we have been referencing what FDA means in the United States and such. We do not defer to other governmental regulatory agencies in other countries for the safety of our pharmaceuticals, is that correct? Ms. Woodcock. That is correct. Mr. Gonzalez. Thank you. I yield back. Mr. Pitts. The chair thanks the gentleman and recognizes the gentleman Mr. Shimkus for 5 minutes for questions. Mr. Shimkus. Thank you, Mr. Chairman. Dr. Woodcock, thank you. You are not an economist, and although we have a lot of physicians on the committee, most of us are not, so you are in good company here. From your opening testimony, the words I caught on to was the drug lag, R&D, investment, fewer drugs because of that. We are going to have a venture capitalist, I think, on the second panel, an investor, talking about, and that is where we are trying to marry how do we keep capital going into this. I don't mind talking about the great job creating aspects of a thriving pharmaceutical industry that is putting safe and efficacious drugs out on the market. At a time when we are looking for job growth, that sector can do that, the telecommunications sector can do that, the energy sector can do that. But as my friend Charlie Gonzales was talking about, we still want it safe, and that is a big criteria. Globalization does play a big role, another word in your opening testimony. So it is in these concerns that we--the issue of our European competitors, who have some quality standards, may be starting to close that gap, plus Asian producers who may be closing that gap. But we have had concerns about what we receive there. This committee has had numerous testimony on stuff, not just on pharmaceuticals, but also, just food products and stuff that has been of great concern. Some of us have been focused on the antibiotics issue, which I would like to turn to a little bit, bacterial resistance to antibiotics, which I know is a concern to you all. Part of your guidance there was some concern that your agency was not giving adequate guidance for clinical trial design for new antibiotics, especially in the case where no treatment existed for a given infection. Can you discuss what progress the FDA has made in this area since you last testified? Ms. Woodcock. Certainly. We have been working with the foundation for NIH that convened a group that is working on endpoints for clinical trials for different classes of antibiotics. I think this is very promising. We also have been having discussions about basically untreatable infectious diseases, multiple drug-resistant infections and how one would do trials, and we do hope to get out some guidance on that. We don't know either, all right? This is unchartered territory. So we can put our best ideas forth, but we don't have all the answers about how to study these. I think we will show considerable flexibility in the standards that we apply when we are talking about diseases, infectious diseases that really lack any alternative treatment. Mr. Shimkus. Can you give me any thoughts on the need for new antibiotics to treat resistant infections? Ms. Woodcock. The bugs are always ahead of us, all right, and that is something we just have to live with, that the infectious organisms can mutate very rapidly. We give antibiotics out to a lot of people. We put the bugs under selective pressure, and bingo, we have resistant organisms that we can't treat very well. So this is an ongoing problem where we need a robust pipeline of new antibiotics, and to some extent, we need some effective antibiotics that we don't use very much, all right, that we hold in reserve for those types of situations, because if we use them broadly, then the bacteria become resistant. Mr. Shimkus. On a separate issue now, talking about the FDA advisory committee and situations in which an individual may be disqualified because they have worked on a clinical trial for an unrelated product, not a related product, and that is, I think, an issue--is that true? Do you know of cases where someone has been disqualified because they worked in a clinical trial for an unrelated product, and does that hurt in this clinical time lag that we are kind of debating today? Ms. Woodcock. Yes, it is true. It is also true we have difficulty recruiting qualified people and having highly qualified panels. In some cases, we have had to delay advisory committees because of the difficulty, because once we go through in great detail, all the financials of the individuals we have nominated, we find that they have to be excused from participating. Mr. Shimkus. Thank you, Mr. Chairman. Thank you, Dr. Woodcock. Mr. Pitts. I thank the gentleman and recognize the gentlelady from California, Ms. Capps, for 5 minutes for questions. Mrs. Capps. Thank you, Mr. Chairman. And thank you for your testimony, Dr. Woodcock. I would like to reiterate for a minute what others on the panel have been saying. The PDUFA program has largely been a successful and creative partnership, in my opinion. And I look forward to working with my colleagues on both sides of the aisle to strengthen the program during this reauthorization process. Moreover, I think a lot of what we have heard today reinforces the importance of giving the FDA the resources it needs to ensure that the agency can do its work independently and in a timely manner while ensuring patient safety. While the FDA's drug review process has a great number of strengths, I am concerned about reports that clinical trials data submitted to the FDA do not routinely include reporting based on sex or other important demographics. For example, one study found that, despite FDA regulatory requirements that require the reporting of a broad range of demographic data, more than one-third of the time this information is not being provided. In addition, a 2007 study specifically looking at heart disease clinical trials--and, of course, heart disease being the number-one killer of women--found that only 25 percent of trials report sex-specific results in scientific journals. These issues were highlighted in a 2010 Institute of Medicine report entitled, ``Women's Health Research: Progress, Pitfalls, and Promise,'' which found that--and this is a quote from the report--``inadequate enforcement of recruitment of women and of reporting data by sex has fostered suboptimal analysis and reporting of data on women from clinical trials and other research.'' Its recommendations included specific strategies for the agency. And another quote from them, which I am sure you know about: ``For medical products, drugs, devices, and biologics that are coming to the market, the FDA should enforce compliance with the requirement for sex-stratified analysis of the efficacy and safety and should take those analyses into account in regulatory decisions.'' Unfortunately, as you know, there is a limited transparency with these applications, making it difficult for the public or prescribing physicians to know if any improvements on this data collection are being made. So my question is, can you discuss this work with us, please? What has FDA done to address the gaps in these data? Ms. Woodcock. Well, interestingly, when I started at the Center for Drugs in 1994 for the first time, I was instrumental in getting this regulation done that required reporting by sex, of how many women were in trials, you know, what the results were by sex and so forth. I don't know the answer to your question. I am going to have to get back to you. My impression was that we have standard tables on reporting by sex, both for outcomes as well as how many people were recruited in the trial and all the other variables. So I am very surprised to hear what you have to say, and we can get back to you on this. Mrs. Capps. Well, I do--I think this is really important. I want to make sure that--there are a number of diseases, not just heart disease, that have different symptoms for the different genders. And I am under the impression and this article would give--the Institute of Medicine report in 2010 would indicate that there is limited transparency within that application process. So that it would be very difficult for the public, it would be difficult for FDA, and it would certainly be difficult and challenging for the medical provider to know if any improvements on the data collection are being made. And I look at the legislation I have introduced in this-- that passed out of the House in the past, the HEART for Women bill, which specifically addresses this issue to ensure that these important data are being used to keep all Americans healthy. So if you have any final thoughts--this is a topic I want to see thoroughly explored by the Food and Drug Administration and a report submitted back to us on whatever findings that you have. Ms. Woodcock. I think part of the problem that we have in getting timely data on this and providing it is that we don't get all the information in a standardized electronic format. If we did that, we could easily run reports on these standard tables and we could tell everything there is to know about reporting by sex. In the new PDUFA recommendations that we are putting forth, there is a requirement that we get standardized all-electronic data. And this would extremely help transparency of this issue and many others. Mrs. Capps. Mr. Chairman, I think this is a really important topic. And I would like to request that we have follow-up data that you provide, FDA provides, to us on the progress that has been made and/or any other changes that should occur so that we can get this information. Ms. Woodcock. I would be happy to do so. Mrs. Capps. Thank you very much. And I yield back. Mr. Pitts. The chair thanks the gentlelady and recognizes the gentlelady, Ms. Myrick, for 5 minutes for questions. Mrs. Myrick. Thank you, Mr. Chairman. And thanks for being here and for your thoughtful comments today. My concern is about the FDA's ability to approve potential drugs to treat deadly diseases. For example, we know a drug like Avastin has toxicities that aren't well-tolerated by some patients, but for some patients, especially metastatic breast cancer patients, it does not extend their survival, but for others it does extend their survival. And metastatic breast cancer patients are facing a deadly disease, as we all know, and many are willing to take that toxicity risk if the drug helps keep them alive. I believe you said that in your testimony today. And so I applaud your efforts, you know, to promote the need for biomarkers and screening tests so that scientists and physicians have more certainty about which patients respond to certain particular treatments. But if we don't have the screening tests now, I don't think we should restrict access or pull approval for a drug simply because we are not sure how to define the category of patients who will respond. So why can't the FDA approve the drug with appropriate warnings for doctors and patients by informing the doctors that many of their patients might not respond and that there are risks involved, I mean, as an example? Ms. Woodcock. Well, I cannot comment on the Avastin situation very specifically. The Center for Drugs has made a recommendation, and now it is before the FDA commissioner. And we have had a hearing and so forth. Generally speaking, if we have found that a drug saves lives, then we will approve it, regardless of many serious side effects, as long as the survival advantage is not outweighed by mortality caused by drug side effects, OK? Mrs. Myrick. Yes. Ms. Woodcock. So we have many, many drugs--we have recently approved several cancer drugs---- Mrs. Myrick. Right. Ms. Woodcock [continuing]. That are very toxic---- Mrs. Myrick. Right. Ms. Woodcock [continuing]. All right? And people know, if they are going to take those drugs, they may be facing--they may die from the side effects. That is true of cancer treatment. But they are trying to extend their lives. Mrs. Myrick. Well, I know there are women who have taken this particular drug, Avastin, you know, for 3 or more years, and they are still doing well, so. I understand, it is just a little frustrating, because I know if you are in a position where you really have this disease and you want to do everything you can to extend your life. One more question on this same line. The FDA and the European Union's drug-approval body reviewed the same data on Avastin as a metastatic breast cancer treatment. And I understand it is approved there for HER2-negative metastatic breast cancer, and it is widely used in Europe for those patients. So what is the difference? How do you explain the difference between what they are doing and what we do? Because I know it is all global, and we look at all of it together. Ms. Woodcock. We do look at all the same data. We have certainly talked to the EU about their decisions. Sometimes we reach different decisions. We approved Avastin for a deadly brain cancer---- Mrs. Myrick. Right. Ms. Woodcock [continuing]. Called ``glioblastoma'' that they did not approve Avastin for. So sometimes various experts come to different opinions. But I can assure you that we have--our breast cancer oncologists at FDA are dedicated to the treatment and, hopefully, eventual cure of breast cancer and getting the best possible agents out there for women. Mrs. Myrick. Oh, no, I don't have any question about that. I guess my question is more about the fact of how we restrict some of these when they do work for a large share of women, even though there is a mortality rate in allowing the usage for those women for those drugs. Ms. Woodcock. The trials that we looked at--and this is from the Center for Drugs, again, because it is up on appeal right now--but in the trials that were done of Avastin in breast cancer, there was no survival advantage at all. And there was also no---- Mrs. Myrick. But--and I understand. But the point is, if it is helping some people and they are willing to take the risk, I guess I go back to the same thing, should we not allow them to have that opportunity? And that is really where I am coming from. Ms. Woodcock. I understand. Mrs. Myrick. I yield back, Mr. Chairman. Mr. Burgess. Would the gentlelady yield to me for a moment? Mrs. Myrick. Yes. Mr. Burgess. Just on that question on Avastin, just looking at the list of people who were on the advisory panel last week who rendered this opinion, I don't see anyone--maybe you can educate me differently--I don't see anyone that would have had the ongoing daily treatment of breast cancer patients under his or her control. You had a lot of experts and a lot of oncologists, but I didn't see a specific specialist in the specialty of metastatic breast cancer. Wouldn't you want someone like that on a panel rendering that type of opinion? Ms. Woodcock. Well, this was not run by the Center for Drugs, and so I can't comment. I agree, there was no breast cancer expert, to my knowledge, on that panel. Mr. Burgess. Thanks, Mr. Chairman. Mr. Pitts. The chair thanks the gentleman and recognizes the ranking member of the full committee, Mr. Waxman, for 5 minutes for questions. Mr. Waxman. Thank you very much, Mr. Chairman. Ms. Woodcock, good to see you again. I mentioned in my opening statement that we want to ensure that innovation in the pharmaceutical industry is vibrant. This is an important national priority. I also think it is important to assure that the drugs that reach patients are both safe and effective. That is the mandate to FDA. When critics assert that FDA is somehow stifling innovation, we need to look very carefully behind those claims and insist that we have reliable and accurate data to substantiate them. Without this kind of data, we can very quickly get to a place where the so-called solutions are being proposed to a problem that may or may not exist in the first place. The same critics allege FDA's slowness is because of regulatory changes that I fear could prove--they are suggesting some of these regulatory changes--for instance, some have suggested that Congress pass legislation preventing FDA from having the ability to insist on critical trial data that FDA feels is necessary and force it to approve drugs on the basis of less information. Specifically, some have also suggested that the FDA be required to approve drugs for certain conditions on the basis of a single study instead of two randomized, placebo-controlled trials. In 1997, we did adopt a law that gave the FDA discretion to do less than two randomized trials, and then we hear critics claiming that FDA has not used this discretion, always insisting on two trials. Now, we are not scientists; we rely on you to make scientific decisions at the FDA. But we hear all the time about how FDA is taking too long and asking for information that is not necessary. Can you comment on this? Is it true that FDA has failed to use the discretion we gave you in PDMA and that the agency always insists on two trials? Would FDA be concerned about legislation that spelled out the number or type of clinical trials that the agency could look at in assessing a drug application? Ms. Woodcock. Well, first, let me say, I would be concerned about trying to legislate at a more detailed level what type of evidence is required. We try to match the evidence to the situation, the requirement of evidence to the situation. So for rare diseases or mortal diseases, less evidence usually is required. For example, we did a study of orphan data, and half of orphan approvals were based on a single trial, one trial. Recently, this year, we have approved seven orphan or rare disease indication, all right? Some new products, some efficacy supplements. For one of those, there was no human trial--it was done on animal data--to show efficacy, right? In one of them, there were 17 patients. And this was a rare disease. But there wasn't a randomized trial. We compared how the patients were doing before they took the drug compared to how they did after they took the drug. Mr. Waxman. So you use that discretion like you have under the law to set up priorities, how serious the disease is, how small the population may be that is being affected by a particular disease or would be helped by a particular drug. And you feel that if we micromanaged your activities by specifying that this trial is all that is needed or that trial is sufficient, that we would end up with, what, stultifying FDA or not letting you do your job? Ms. Woodcock. We might slow things down. Mr. Waxman. Slow them down even further? Ms. Woodcock. That is what I think, because we would be involving a lot of lawyers and whether we were obeying the law in medical decisions that we were making. Nothing against you lawyers, but sometimes that slows things down a little bit. I would say that we have considerable flexibility. And, say, a drug for headache pain that is going to be used by millions of people, all right, you want to know more about that--you want to know it is not going to cause a stroke, for example--than a drug here for the orphan indication or for a disease where people are dying and they don't have any other alternatives. We have great flexibility in the standards that we apply. Mr. Waxman. Has there been a change in FDA's protocols for reviewing drugs? In other words, has there been something where, according to Mr. Leff, who is going to testify in a while, that FDA has shifted to a more cautious decision-making posture, begun to require more and more data to provide a higher degree of statistical proof of both efficacy and safety? And it sounds like FDA has somehow formally changed the drug review process. Is that an accurate statement? How do you respond to that? Ms. Woodcock. No. I believe that we still have the standards of safety and effectiveness that we have always had, and we continue to apply them. We have learned, though--we have learned some things. For example, we have learned that drugs that raise blood pressure will cause a certain incidence of strokes. And so, for example, in obesity, if you are going to have a drug to treat obesity, maybe it causes weight loss, but if it raises the blood pressure--I mean, you are treating the obesity, in part, to decrease cardiovascular complications, OK? Mr. Waxman. Right. Ms. Woodcock. What if, in fact, you are actually going to increase them? So we have to know, because the standard is that it works, right? And patients take these drugs because they believe they are going to better their lives and better their health. And so, when we learn new medical facts, new scientific facts, we have to make sure that they are taken into account in the drug development program. But that is part of the standard of safety and effectiveness. Mr. Waxman. Thank you, Mr. Chairman. Mr. Pitts. The chair thanks the gentleman and recognizes the gentlelady, Ms. Blackburn, for 5 minutes for questions. Mrs. Blackburn. Thank you so much, Mr. Chairman. And we appreciate that you are here, Dr. Woodcock. I want to stay with the line of questioning that Ms. Myrick had started with you, looking at this approval process. I had gone through the forensic cancer research report on FDA and the EMA, European Medicines Agency, looking at those approvals from 2003 to 2010. And, you know, that said, well, FDA was faster than EMA. But when you look at the year by year on that--and I am sure you have done that--and you go back to 2007 or 2008, there is a significant narrowing of the lag in cancer medicine approval times between the FDA and the EMA. And that was repeated--the noting of that lag was repeated in the California Healthcare Institute--and I know you are familiar with that report--and also the Boston Consulting Group report. So I want to ask you four questions relative to that, because I think this should be of great concern with us. And it ties into what we hear from our constituents, who are concerned about the process that you are having individuals go through, as they try to file and go through the approval process. So here are the four questions for you on that: Number one, what accounts for these trends? Number two, is the FDA getting slower and more inefficient? Number three, is the EMA getting better and more efficient? And, number four, is it a combination of things? Because if we are getting slower, we need to nip this in the bud and we need to know what the precise problem is. Can you define that? Ms. Woodcock. Well, I can't remember each one of your four questions---- Mrs. Blackburn. I will be happy to submit for writing. Ms. Woodcock. Right. The FDA most recently--our most recent data for 2011 show that we have the highest first-action approval rate we have ever had, which means the applications are coming in and they are getting out the door on the first cycle. And that, for priority applications, is 6 months usually. All right? So you can't get too much faster than that, all right? The Europeans may be getting faster. Another hypothesis or thought is that the applications are getting better, all right? If the industry fully understands what the regulators want and they have a very important drug that is needed by the population, then it usually will move through the regulatory process in any country very rapidly. So we don't feel we are in competition with the European Union or whatever. We were simply responding to criticism that it was taking us twice as long or three times as long as they. If the drug were approved simultaneously around the world and available to all patients with whatever disease, say, hepatitis C, that would probably be the best outcome. Mrs. Blackburn. Well, and I agree with you on that. And I think that the two things that we hear you could kind of distill down to companies that are spending billions of dollars, want to make certain that they are provided with both transparency and consistency in that FDA review process. And they want to make certain that you all are conducting these with certainty and predictability. And as you well know, that has been a problem. One other question I wanted to ask you about, because I have written you about the PGAs and the issue that is there. And I was due a response--I am trying to find it--by the end of June, and I still have not had a response from you all about the products that are there, with the PGAs and what you are doing with those over-the-counter, unapproved, PGA-containing eyelash growth products. What are you doing to investigate the marketing of those products and to restrict those in the marketplace? And do you plan to take enforcement action against all companies marketing these companies without FDA approval? I think that all of us who look at the market for young women, we are very concerned about these products in the marketplace. Ms. Woodcock. Yes, we are looking into this issue. As you know, there are numerous products in the marketplace, dietary supplements, that have been contaminated with many dangerous drugs. And so we have been taking action on products that are contaminated with these drugs. And we are looking into this issue, and we will be happy to get back to you on our progress. Mrs. Blackburn. OK. I am speaking specifically of the eyelash---- Ms. Woodcock. I know. Mrs. Blackburn [continuing]. Growth. Ms. Woodcock. I know. Mrs. Blackburn. OK. Well, we were due a response by the end of June. Ms. Woodcock. Yes, I am sorry that you have not received that in a timely manner. Mrs. Blackburn. OK. And I think that we want to know that there is action taken against these unapproved---- Ms. Woodcock. Yes. Mrs. Blackburn [continuing]. Products. Thank you. I yield back. Mr. Pitts. The chair thanks the gentlelady, recognizes the gentleman, Mr. Engel, for 5 minutes for questions. Mr. Engel. Thank you, Mr. Chairman. I want to thank you for holding this important hearing today. As we all know, the reauthorization of PDUFA is vitally important to both patients and industry alike. As many of us remember, PDUFA was originally enacted in 1992 to address the unusually long and unpredictable wait period that it used to take for new drugs to be approved for market consumption. At that time, it would take an average of more than 2 years for a new drug to be approved, which meant that patients would not have access to new medicines when they needed them, and innovation suffered. I am proud to say that, since then, we have come a long way in making more drugs available to patients while maintaining safety. I recognize that the system is not perfect, but we have come a long way. Mr. Chairman, as we move along in the reauthorization process, I look forward to working with the various stakeholders and my colleagues on the other side of the aisle to address ways in which Congress can strengthen the FDA and achieve our common goals. I mention working with my colleagues on the other side of the aisle because I think it is very important that we remember that this is not a partisan issue. However, the appropriations bill that was passed last month cut the FDA's funding drastically, and I think that was a mistake. How can we expect the FDA to do their job effectively and efficiently while at the same time take away the valuable resources they need to do it? This only hurts patient safety, and it also hurts one of our strongest and most innovative industries. So, Dr. Woodcock, let me ask you this. Today we are discussing legislation that authorizes prescription-drug user fees, which are critical to the FDA's ability to approve drugs more quickly while at the same time the House is cutting the funding. Can you tell me how you plan to reconcile these cuts and see that new, innovative drugs continue to come into the market in a timely manner? Ms. Woodcock. Well, I mean, any cuts would make various programs at FDA more difficult. We also approve generic drugs, and the flow of those is important to keeping health-care costs under control in the United States. And we would become more challenged, I think, in our review of generic drugs if we had substantial cuts. We also manage post-market drug safety problems, and that requires a considerable amount of resources and effort. We also keep guard over quality of all the drugs in the United States. And, as has already been mentioned, the import of drugs from all around the world and manufacture around the world have challenged us to make sure that we are able to ensure high quality of the U.S. drug supply. So that would be a challenge. Also, clinical trials are conducted all around the world, and so we are having to inspect those clinical trials wherever they might be held. In addition, as you alluded to, this would have an impact on our ability to promote innovation in new drug regulation and in drug development, which is something that is very dear to my heart. Mr. Engel. Let me ask you--as you know, many doctors and hospitals are struggling to cope with unprecedented drug shortages in the United States. Drug shortages obviously lead to delays in treatment and force the use of alternative drugs, which can result in unintended consequences. This shortage is endangering cancer patients, heart-attack victims, accident survivors, and many other ill people. So let me ask you this. Before I ask you this, I want to ask the chairman for unanimous consent to put into the record a statement from the American Hospital Association on behalf of our hearing today. Mr. Pitts. Without objection, so ordered. Mr. Engel. OK, thank you. Thank you, Mr. Chairman. [The information follows:] [GRAPHIC] [TIFF OMITTED] T2917.031 [GRAPHIC] [TIFF OMITTED] T2917.032 [GRAPHIC] [TIFF OMITTED] T2917.033 Mr. Engel. So let me ask you this, Doctor. From the FDA's perspective, what is the problem with drug shortages, and how can we address it? Ms. Woodcock. Drug shortages have multifactorial problems, all right? They are related, often, to drugs that are off- patent, that only have one manufacturer that is approved in the United States, and that eventually have aging facilities. We work tirelessly to try and ameliorate drug shortages in the United States. And, from our point of view, although there are these structural problems, what would help us the most would be to have early notification if a company is planning to stop making an essential drug or temporarily go out of production, so that we could make arrangements to substitute something else, to get another drug available for doctors and patients. And we have been able to do that many times when we have actually had advanced notice. Mr. Engel. Let me ask you--the final question is, you mentioned in your testimony that the FDA allows access to investigational products through clinical trials. And this allows patients who may need a treatment that is not currently on the market to access innovative treatments. You mentioned also in your testimony that are times when patients cannot enroll in critical trials. Could you explain why and what some of the challenges are that these patients face when considering the clinical trial? Ms. Woodcock. Well, there is difficulty in the U.S. in accessing clinical trials. But there is a broader issue of treatment access, which is a person who lacks alternative therapy and there is no other approved drug that might work for them, so they would like to access an investigational product-- drug. We recently passed regulations about a year ago that broadened and liberalized and rationalized access protocols for investigational drugs. The FDA believes that people with serious illnesses who lack alternative therapy should be able to get investigational drugs on a treatment basis. Mr. Engel. Thank you, Mr. Chairman. Mr. Pitts. The chair thanks the gentleman and recognizes the gentleman from Georgia, Dr. Gingrey, for 5 minutes. Mr. Gingrey. Mr. Chairman, thank you. And, Dr. Woodcock, thank you very much for your testimony. Let me ask you a couple of quickies. Did you tell the committee that your specialty is rheumatology? Ms. Woodcock. Yes. Mr. Gingrey. OK, thank you. In regard to my colleague from North Carolina, in regard to the question on Avastin, can you assure the committee the decision on Avastin--and I guess that final decision is in the hands of the commissioner at this point; it looks like it probably will not be approved for advanced breast cancer, although it will continue to be approved for colon, and you mentioned a type of brain cancer that it is still approved for--this decision, can you assure us, is not based on the cost of that drug? Ms. Woodcock. We never look at the cost of drugs when we are doing our decisions. It is not within our mandate, and it is not something that we look at. Mr. Gingrey. You never look at the cost of the drug? Ms. Woodcock. No. Mr. Gingrey. OK. Mr. Shimkus brought up a question about the need for new antibiotics, and I think that your response to his questions was reassuring to me. And I think you probably know that Mr. Shimkus and myself and others on this committee, in a very bipartisan way, have introduced H.R. 2182, the GAIN Act, to try to get more antibiotics to the market and the problems that we have in regard to that, because if they are used properly, then the market for the sales of those drugs is very limited---- Ms. Woodcock. Right. Mr. Gingrey [continuing]. As it should be, if they are used properly. Can you also give me your thoughts on the need for new diagnostics to properly identify infectious diseases? For example, would new diagnostics have helped in the recent E. coli outbreak in Germany? Ms. Woodcock. Certainly. We feel that, particularly, point- of-care diagnostics that could be used at the bedside by clinicians to rapidly identify the bacteria and also potentially resistance profiles would be just an outstanding advance in infectious disease. And we have certainly talked to the Infectious Disease Society about this and others. So if we could target our antibiotics better--as you well know as a clinician, we do a--whatever you call it--a shotgun approach to treatment until we have the cultures and we know what the patient has. And so, for many days or maybe total course of treatment, it may be empirical, and so we don't know what we are treating. And this leads to a more widespread resistance, I believe. Mr. Gingrey. And that, of course, is part of our bill, as well. And I thank you for that response. Very quickly, my last point, I wanted to address the Sentinel Initiative, the post-market risk identification/ analysis system. And the reason I wanted to be sure of your specialty of rheumatology, there is a drug--I think it is pronounced ``Remicade.'' Am I correct? Ms. Woodcock. Yes, uh-huh. Mr. Gingrey. --Remicade, that was approved. And I wanted to ask you, if you know, was that approved under orphan drug status? I know it has been on the market maybe for as much as 20 years--well, maybe not quite that long. But the drug being used for Crohn's disease and with pretty good results. But my understanding is that up to 5 percent of individuals will eventually, if they have taken that drug for Crohn's disease, they will eventually come down with leukemia. And, you know, to me, that seems awfully high. And maybe I am being affected because it happened to a family member just recently, who ended up dying of her leukemia. She was helped tremendously several years ago by use of this drug. What is the threshold? A 5 percent, to me, risk from taking a drug and then ultimately developing leukemia, which is pretty life-threatening--in her case, it was definitely life- threatening and life-ending--where is the threshold in regard to what we are looking at in the Sentinel Initiative, the post- market analysis of these drugs? Ms. Woodcock. Well, generally what we are doing with all the immunosuppressant drugs is having registries and long-term follow-up. So we can also use Sentinel for evaluating these longer-term outcomes. But we are also watching patients observationally over time. And we can get back to you on what we know right now about the occurrence of malignancies as well as infections, opportunistic infections, as a result of all the classes of immunosuppressive drugs that are used. Mr. Gingrey. Dr. Woodcock, I would really appreciate that, both as a Member of Congress and personally. I would really appreciate you getting back to me with a report on that. And I thank you very much. Ms. Woodcock. I would be happy to do that. Mr. Gingrey. I yield back. Ms. Woodcock. And if I may say one thing about this, this really illustrates the balance of benefit and risk, because malignancies are not apparent immediately, all right? And so, you could say, well, this is a wonderful drug, we should just get it out there, and everyone should take it. But what we find out is, yes, there are breakthrough--tuberculosis, whatever, and there are also cancers that occur late. And this is where we have an obligation to patients to find out as much as we possibly can, so they can make their decision. Mr. Gingrey. Thank you. Mr. Pitts. The chair thanks the gentleman and recognizes the gentleman, Mr. Latta, for 5 minutes for questions. Mr. Latta. Well, Doctor and Director, thanks very much for being with us today. I really appreciate your testimony today. And just to kind of maybe follow up a little bit of the questioning that has already been asked, but one of the areas that I would like to go into is about especially on the obesity and diabetes side, with the drugs out there and the therapies that are being brought forth, and especially with the FDA approval process. Because, as we all know, especially young and old alike, both these, diabetes and obesity, are affecting a huge portion of our population and increasing our costs. Especially, it is a huge driver on the Medicare side. And the question is, what are you doing to encourage the development of new therapies to treat these diseases, especially using your authority under REMS---- Ms. Woodcock. Pardon me. I am having trouble hearing you. Mr. Latta. OK. You know, this is sometimes also the room that we use for our telecommunications subcommittee. And I am sorry--is that better? Ms. Woodcock. Yes. Mr. Latta. OK. The way some of our mikes pick up. But the question I have then is, what are you doing encourage the development of new therapies to treat these diseases, especially using your authority under REMS to follow the drugs closely after their approval? Ms. Woodcock. We share the understanding of the need for new treatments for diabetes and for obesity. And I would point out that for diabetes, in early 1990s, there were only two types of therapies available for the treatment of Type 2 diabetes, and now we have 11 new classes of drugs that are out there. So there has been a tremendous blossoming of attempts to get new therapies for diabetes out there. And, in fact, we are seeing the pipeline continue. And we have put out guidance about cardiovascular risk in diabetes drugs that companies have been able to deal with and follow, and we have approved new diabetes drugs recently. So we see a robust pipeline there. In obesity, the problem is different. We have had to take three obesity drugs off the market because they cause stroke. We have had to take another class of obesity drugs off the market because of heart-valve disease. And you can see with young people, if we expose them to an agent widespread that causes heart-valve disease, we would have another epidemic on our hands. So we must make sure that these products have adequate safety. But we recognize the obesity epidemic. And what we are doing is we are going to have a scientific meeting about obesity and cardiovascular safety. And we are also planning to have a series of stakeholder meetings, where we bring in the very attritions and the patient groups and the FDA and other experts to talk about how diabetes drugs should be developed. And I think this will be very helpful to the industry. Mr. Latta. Let me ask this. I think you said that you took several off the market last year. I believe also, if my information is correct, that the FDA also denied three consecutive applications for approval of new obesity drugs last year. Ms. Woodcock. That is correct. Mr. Latta. Now, was that for the same reasons, or what was the cause of that? Ms. Woodcock. Different--well, one drug had a blood- pressure problem, which was the reason we had to remove other diabetes drugs off of the market. They were causing strokes. Last year, we removed a drug, Meridia, from the market because of stroke. A trial was done that showed that even though people lost weight, they still got an increased number of strokes when they took this weight-loss drug. So it was removed from the market. So one of the problems that we are identifying is many of the weight-loss drugs increase blood pressure, and we have to make sure they are not causing an excess of strokes, OK? But some of the other weight-loss drugs have other types of problems that we are looking at. Mr. Latta. Thank you very much. And, Mr. Chairman, I yield back. Mr. Pitts. The chair thanks the gentleman and recognizes the gentleman from Kentucky, Mr. Guthrie, for 5 minutes for questions. Mr. Guthrie. Thank you, Mr. Chairman. Thank you, Dr. Woodcock. I know you all have a difficult job anytime you approve a drug as you go forward. And just think about the long term as you move forward, of course there is a--so it is a quandary. But there are a lot of people waiting on the approvals as you move forward. And my friend, Ms. Myrick, Representative Myrick, covered some of it, but I just got a text this morning from my brother, and I am going to share this a little bit. Well, first, my brother called me yesterday. He has a best friend in the Navy, was in the Navy, whose wife had breast cancer. And they were one of the ones who flew from Seattle, Washington, to, I guess, Baltimore a couple of weeks ago. And the text says, ``Thanks for talking to Nancy yesterday. She knew we were having this meeting. They are great people, and thanks for the quick response. The bottom line is, they have been through a lot, and she has lived much longer than she was supposed to.'' And I really read that to give you that line. And it seemed like with Avastin that--I talked with her quite a while on the phone yesterday, and she said her mother has breast cancer but very localized. And she realizes Avastin wouldn't be something that her mother should be taking. But she did say, when she discovered she had breast cancer, when they found the breast cancer, she had four tumors on her liver. I think that is what she said. And so, therefore, it looked like she had made the decision. She realizes the toxicity, but she really believes that Avastin is--and she is distraught--has really increased her life expectancy. So the question--and maybe this wasn't your area, as you said--was Avastin not approved for breast cancer because of the side effects or because there is no clinical proof that it actually works? Ms. Woodcock. Avastin was approved under accelerated approval for breast cancer. It was already on the market for other cancers, all right? Mr. Guthrie. Right, right. Ms. Woodcock. And then, subsequently, it was approved under accelerated approval. What that means is, then the drug developers have to prove that the promise, OK, that was approved under accelerated approval is real, all right? And so the company did additional trials, and they did not show any survival advantage. The original trial it got approved on showed something called progression-free survival. What that means is you live longer with your tumors not growing on scans. Mr. Guthrie. OK. Ms. Woodcock. All right? It doesn't mean you live longer. It means that your tumors are stable longer. And so the original trial showed, in women getting Avastin, their tumors stayed stable longer, all right? Mr. Guthrie. OK. Ms. Woodcock. What we asked the company to say--well, show that means something, show that translates to either quality of life, better quality of life of the people or longer life of people, all right? And they were not able to show either of those in the subsequent trials that were done. That does not mean that Avastin is not an active drug, perhaps, for some women, but we do not know what women. And it does have very serious, potentially fatal side effects. Mr. Guthrie. Right. She recognized that. We had talked on the phone--and so the issue really wasn't just the side effects and it could be fatal. But you are saying it really didn't show that it extended the life as you move forward. Ms. Woodcock. It did not. In that population. And that is not a population that is selected by some marker to respond well to Avastin. It may well be if they could come up with a biomarker and say, ``These women are the women who should take this drug,'' then it might be possible to figure out who the drug is good for. Mr. Guthrie. Uh-huh. So it could be a--and she could be one---- Ms. Woodcock. That is right. Mr. Guthrie [continuing]. A select group of circumstances that it affects--because drugs interact with all of us differently--that would actually--and I know from our conversations she is convinced that she is still here because she was on Avastin. And one other thing a lot of people have said--I only have about a minute, so I will just ask it really quick. You know, I do hear from a lot of our people in the drug field, pharmaceutical field, saying that they are having difficulty getting things approved. You have heard that from several of us here. You all must be hearing the same thing. And maybe what you are saying is 2011 has been better than 2010 and 2009 and 2007. So are you already acting to the fact that people said they are getting things difficult--like you said, 2011 has been pretty successful, but I am really not hearing people saying that, ``We have had difficulty in the past, but it seems to be getting better.'' So I don't know if you are hearing the same thing. And just comment on that. I have about 40 seconds left. Ms. Woodcock. Well, I would propose to you that the people who come into your office are not the people who have had a successful experience. And so you have what we call a biased sample, all right? And even if, like, 90 percent of the people are getting through and we are having a tremendous--I am not saying all this will continue, but this year we are having an extremely high approval rate because the drugs that are coming in are--many of them are very significant advances, all right? But the people I think who come to talk to you continue to be the people who are having a difficult time. And so I don't know that you would see any change in your experience. Mr. Guthrie. So they are not coming by to see us just to say, ``Thanks, it really went well''? We hear that sometimes too. Thanks a lot. Ms. Woodcock. Thank you. Mr. Pitts. The chair thanks the gentleman, recognizes the ranking member emeritus of the committee, Mr. Dingell, for 5 minutes. Mr. Dingell. Mr. Chairman, I thank you for the hearing. And I thank you for your courage. Ms. Woodcock. Thank you. Mr. Dingell. I wanted to ask a ``yes'' or ``no'' question. I hope you will respond. Do you have the ability to fully control the safety of imported pharmaceuticals, yes or no? Ms. Woodcock. No. Mr. Dingell. Do you have the authority to control the safety of raw materials or imported pharmaceuticals? Ms. Woodcock. No. Mr. Dingell. Do you have the authority and the resources you need to address the safety of components now being imported into this country, yes or no? Ms. Woodcock. No. Mr. Dingell. Do you have the necessary authorities and resources to see to it that drugs are only imported from facilities overseas that are properly observing good manufacturing practices--that is a word of art--yes or no? Ms. Woodcock. No. Mr. Dingell. Do you have the ability to see to it that raw- materials suppliers also engage in good manufacturing practices abroad? Ms. Woodcock. No. Mr. Dingell. Do you have the resources needed to conduct foreign drug-facility inspections with the same frequency as domestic drug-facility inspections? Ms. Woodcock. No. Mr. Dingell. How often can you get by to see a foreign drug manufacturer? Ms. Woodcock. Every 9 years or so. Mr. Dingell. Every 9 years? Ms. Woodcock. Yes. Mr. Dingell. You get by to see dog-food manufacturers every year or so. Ms. Woodcock. Yes, probably a little more--a little over a year. Mr. Dingell. Do you need additional resources to increase inspections of foreign drug facilities? Ms. Woodcock. Yes. Mr. Dingell. Do you need additional authorities to be effective in that? Ms. Woodcock. Absolutely. Mr. Dingell. Do you have the ability to freely share information about a drug with your trusted domestic and foreign counterparts in the instance of something like another heparin crisis, yes or no? Ms. Woodcock. No. Mr. Dingell. Do you need this ability? Ms. Woodcock. Yes. Mr. Dingell. Do you have a clear authority to require manufacturers to assure the safety of their food chain, yes or no? Ms. Woodcock. Their food chain? Mr. Dingell. Yes--I am sorry, the supply chain. I apologize. Ms. Woodcock. Thank you. No, we do not. Mr. Dingell. Do you need this authority? Ms. Woodcock. Yes. Mr. Dingell. Do you have the authority to require manufacturers to notify you if they suspect their drug may have been counterfeited, misbranded, or adulterated? Ms. Woodcock. No. Mr. Dingell. Do you have the ability to properly assure the safety of both raw materials for the manufacture of pharmaceuticals and pharmaceuticals as they are imported into this country? Ms. Woodcock. No. And I think we are one of the few countries that does not have that authority. Mr. Dingell. Do you need this authority? Ms. Woodcock. Yes. Mr. Dingell. Do you have the authority to require companies to recall a drug, yes or no? Ms. Woodcock. No. Mr. Dingell. Do you have that authority with regard to imports? Ms. Woodcock. No. Mr. Dingell. Do you have that authority with regard to raw materials and things like that? Ms. Woodcock. No. Mr. Dingell. And components? Ms. Woodcock. No. Mr. Dingell. Now, let's go to the question of heparin. A lot of bad heparin got out because, currently, you couldn't get over to China to see what the raw material was like and what was safe or unsafe with it. Is that right? Ms. Woodcock. That was part of the problem. Mr. Dingell. What was the other part? Ms. Woodcock. I think the tests were out of date for heparin. Mr. Dingell. The what? Ms. Woodcock. The testing standards, the U.S. standards, international standards. Mr. Dingell. Were they adequate or inadequate? Ms. Woodcock. They were inadequate. Mr. Dingell. OK. Do you have authority to address that problem? Ms. Woodcock. No, not fully. Mr. Dingell. Not fully or just not at all? If you can't do it fully, you can't do it at all, can you? Ms. Woodcock. Can you repeat the question? Mr. Dingell. Would you submit a brief monograph to this committee for the purposes of the record---- Ms. Woodcock. Certainly. Mr. Dingell [continuing]. Explaining what happened in the heparin case and what abilities you need to address imports not just of finished products, pharmaceuticals, but also raw materials and components, please? Ms. Woodcock. We would be happy to do that. Mr. Dingell. Thank you. I ask unanimous consent that the additional matters requested be inserted in the record at the appropriate point, Mr. Chairman. Mr. Pitts. Without objection, so ordered. [The information appears at the conclusion of the hearing.] Mr. Dingell. Mr. Chairman, I thank you for your courtesy. And I thank our witnesses. Mr. Pitts. The chair thanks the gentleman, recognizes the gentleman from New Jersey, Mr. Lance, for 5 minutes for questions. Mr. Lance. Thank you, Mr. Chairman. Good morning, Doctor. I have the honor of being the Republican co-chair of the Rare Disease Caucus. And I want to thank the progress that the FDA has made regarding the advancement of orphan product development. And given the fact that a large number of products approved by the agency are for orphan indications, it is clear to me that the FDA's increased focus on development and approval of orphan products is important to all stakeholders in the rare-disease community. I am particularly interested in learning more about the Office for Rare Diseases, created last year. As I understand it, the goal of that office is to facilitate and support research, product development, regulations and approval of biopharmaceuticals for the treatment of rare disorders and to serve as a focal point for stakeholders and developers of drug and biological products. If one of the primary objectives of the Office for Rare Diseases is to ensure collaboration among scientists and clinicians throughout CDER, what steps are being taken and what are the plans for the future to ensure adequate resources that are allocated to this office? Ms. Woodcock. Thank you. Yes, as part of enhancing regulatory science and expediting drug development within the proposals we have for the new user- fee program, we have a portion on rare diseases, which would improve resources, add additional resources to our attention to rare diseases, including to that office. Mr. Lance. And will you be engaged in that activity? And what time frame, Doctor? Ms. Woodcock. The new user-fee program hopefully will be passed and be able to be implemented in 2013. And, at that point, we would have additional resources to put---- Mr. Lance. So this would be an action probably we would take next year regarding PDUFA, next year? Ms. Woodcock. Yes. Mr. Lance. Thank you. Well, I look forward to working with you and other interested stakeholders in this issue. It is important, I think, to the entire Nation and certainly important to the district and State I serve, which we believe is one of the medicine chests of the world. On a different topic, on biomarkers, innovative drug development is increasingly dependent on the use of new biomarkers of disease to target the right patients. Could you tell us what you are doing to encourage the use of biomarkers in drug development? Ms. Woodcock. Thank you. I think since 2004 FDA has really been in the forefront of this; we have been encouraging the use of biomarkers. And we have published numerous guidances. We have done a lot on something called pharmacogenomics, because a lot of these would be genetic markers. And we also now have a proposal in the new user-fee enhancements where we would like to enhance our activities on biomarkers and pharmacogenomics, because we feel this does have tremendous promise for patients and for drug development. Mr. Lance. Well, thank you, Doctor. This is my first opportunity to meet you. I am new to the committee, and I look forward to working with you. And I yield back the balance of my time. Mr. Pitts. The chair thanks the gentleman and recognizes the gentleman from Louisiana, Dr. Cassidy, for 5 minutes for questions. Mr. Cassidy. Thank you, Dr. Woodcock, for testifying. Newly active substances, just so I am clear on the definition, if somebody has a drug and they make it a single- day therapy, a prolonged release if you will, as opposed to a QD, does that qualify the new--so it is just a truly new drug? Ms. Woodcock. Yes, it has to be first, you know, time and first exposure to humans of this molecule, basically. Mr. Cassidy. Got you. Secondly, just to follow up on what Mr. Dingell asked about, man, if you are inspecting dog-food factories a little bit over a year but only going abroad every 9, couldn't you redirect resources from the dog-food factory--I am saying that as a pet owner--to--and, of course, it sounds tongue-in-cheek, but, actually, it is a very serious question. Ms. Woodcock. Well, Congress directs resources to drug programs separately from foods or veterinary medicine. So they are all separated out, and we have to expend those based on the appropriation, OK? Mr. Cassidy. So, would it be--not to put you in a box, but if Congress redirected some of the funds currently used for dog food, as an example, metaphorically if you will, to inspecting companies abroad to make sure they have good clinical or good manufacturing practices, would that be a reasonable thing? Ms. Woodcock. Well, I think, then, that is a tradeoff. The Congress has recently asked FDA to accomplish a great deal more tasks under food safety, with their new food-safety bill. And those inspectors are all busy trying to accomplish those activities. So we have tried--we are trying to redirect domestic inspection resources to do overseas inspections. And that has been the main effort that we are working on. Mr. Cassidy. So, then, to follow up that, one thing you could do within this silo, almost, of funding is--because I have had domestic drug manufacturers complain, ``Listen, I am checked every 6 months, and yet my competition is checked every 9 years.'' It isn't a competitive issue for them; it is a drug- safety issue. So could you elaborate a little bit more on that occurring? Because it seems a very reasonable approach. Ms. Woodcock. Yes, I think that we are moving--we have been trying to move in that direction. That is a desirable thing to do, to have a uniform level of inspection around the world that is also risk-based, OK? So the riskiest plants should receive the most frequent inspections, whether they are in the U.S. or whether they are in China or elsewhere. It has just been logistically very difficult to accomplish this. Mr. Cassidy. Now, again, just to, again, pursue--it just seems so logical. I mean, you are going to go buy a ticket to go to Bangalore and inspect the plant there. Why would that be logistically complicated instead of going to New Jersey? Granted, New Jersey is a train ride and Bangalore is a trip. But, nonetheless, it does seem as if maybe it is a prejudice, that probably the people in New Jersey have better practices or one that we trust more than maybe just a startup in Bangalore? Ms. Woodcock. Yes, the inspections are done by our field organization. It is not a part of the Center for Drugs. And they have a union, and they have agreements about foreign travel and how much you can get people to go and do things overseas. Mr. Cassidy. You mean there is a union agreement which is keeping us from being able to inspect foreign manufacturers? Ms. Woodcock. Partly. That is my understanding. Mr. Cassidy. You mean the union agreement is keeping us from inspecting these more frequently than every 9 years? Ms. Woodcock. Well, the work conditions. It is just very difficult--my understanding; I don't supervise that organization--to shift resources to have a larger number of foreign inspections done. Mr. Cassidy. I have to admit, as a physician practicing, it gives me great concern for the safety of my patients that that is what is limiting our ability. Ms. Woodcock. We would be happy to get back to you with a more complete explanation. Mr. Cassidy. Please. Because that is so incredibly troubling. Which union is that? Ms. Woodcock. Pardon me? Mr. Cassidy. Which union is that? Ms. Woodcock. NTEU. Mr. Cassidy. I only have 50 seconds left. Let me gather my thoughts after that. If we had not had that union agreement, would the heparin tragedy have been avoided? Ms. Woodcock. I think it would still be difficult to move people from their established inspection routine and get them to travel repeatedly overseas. Mr. Cassidy. Why don't we just---- Ms. Woodcock. But we are moving in that direction. Mr. Cassidy. It may be difficult with the current employees, but it sounds like, if that is where the problem is, then we just need to find employees that will go, correct? Ms. Woodcock. Well, there is also a problem with resources. I don't want to understate that, OK? That it is going to take more people to do all of these inspections overseas, and it would--it is not as efficient as inspecting a certain number of plants in a certain geographic area. Mr. Cassidy. I accept that. But, on the other hand, if you are going to find out where the problems are, and if we can trace them--the bulk of them to these companies overseas, manufacturing plants overseas, it just seems that is where you should be looking. Ms. Woodcock. Well, we definitely should go where the money is. But I would say that we have certainly found manufacturing problems domestically recently. Some of them have been high- publicity problems. And we have to maintain good coverage of those firms, as well. Mr. Cassidy. I accept that. On the balance, what would be the percent of the domestic versus foreign that have resulted in deaths? Ms. Woodcock. I don't think we have that kind of data. Mr. Cassidy. OK. I yield back. Thank you. Mr. Pitts. The chair thanks the gentleman, recognizes the gentleman from Pennsylvania, Dr.---- Mr. Dingell. I forgot to ask one question. Could I ask just one question? Mr. Pitts. Go ahead. Please. Mr. Dingell. To the witness, if you please, H.R. 1438, the Drug Safety Enhancement Act of 2011, would this afford you the authorities you need to deal with the heparin problem? Ms. Woodcock. Yes. Mr. Dingell. It would. Ms. Woodcock. Yes. Mr. Dingell. Would you give us a little memo on why that is, for inclusion in the record? Ms. Woodcock. We would certainly be happy to. [The information appears at the conclusion of the hearing.] Mr. Dingell. Mr. Chairman, you have been enormously courteous, and I thank you. And I apologize to my colleague for having interfered with his time. Mr. Pitts. That is all right. The chair thanks the gentleman and recognizes Dr. Murphy of Pennsylvania for 5 minutes. Mr. Murphy. Welcome, Doctor. It is good to have you here. Ms. Woodcock. Thank you. Mr. Murphy. There was an article in yesterday's Wall Street Journal written by Roger Bate. I don't know if you had a chance to see that. But in that, he pointed out a number of things about the risks that come to western firms from these small, hard-to-detect flaws, with the trace impurities from unhygienic practices, which seems to summarize what we are dealing with here. The FDA--excuse me--the Federal Food, Drug, and Cosmetic Act provides a drug is adulterated unless the methods used for the manufacturing of a drug product conform to current good manufacturing practices. Can you explain the role and importance of the good manufacturing practices that FDA looks at in their approved products? Ms. Woodcock. Good manufacturing practices are a quality system, and you are probably familiar with quality systems from other areas of manufacturing. These really apply to mass production. So it is one thing to make a drug in a laboratory and have a lot of scientists looking over it. It is another thing to make it in a factory and make millions of doses and make them repeatedly sterile, potent and uncontaminated, and that requires adherence to a quality management system. The good manufacturing practices is a set of codified regulations that FDA has that establishes kind of the minimum standards for doing that. Mr. Murphy. Now, you have talked about the supply chain. I know Mr. Dingell brought that up, too. So what is preventing the FDA from updating its GMPs, requiring drug companies to verify their suppliers are complying with the law on providing quality ingredients? Can you tell me a couple of items there that are preventing you from doing that? Ms. Woodcock. Well, it is possible with a very long process, we could modify some of the good manufacturing practices regulation, but others--I think of the things that Mr. Dingell--other authorities that he was referring to would require legislative authorization. Mr. Murphy. In part of looking at that, you understand that this entire Nation is looking upon Congress to find ways to save money and also to look at health care costs, particularly Medicare and Medicaid which is spinning out of control. Is the FDA involved in or do you know of any other Federal agencies looking at a number of aspects? For example, when we look at some of these medications, and the estimates are, as an example, as much as 5 percent of ingredients may be impure, may have impure drug content, and we are looking at $1.74 billion and rising of imports here. Does anybody have any information on the impact on health care, such as drug shortages, and what that means to health care costs, tainted drugs that then effect extended stays in hospitals, return visits to physicians office and emergency rooms? Is that something that you or anybody else is studying the impact on health care costs? Ms. Woodcock. I wish we had that kind of data, but we do not. It is very difficult to link drug quality health problems with health outcomes, and Heparin was a dramatic example where we saw that. But we don't have overall data like that, and I don't know that anybody else does. Mr. Murphy. Well, that is certainly troubling. While we are looking at this, I know that studies have said just when patients--when patients, we have looked at something like 75 percent of people don't take their medication properly and a study recently said that is a $250 billion drain on the system. But then when they do take medications according to doctors orders, and we find out there are flaws with some of the content of generic drugs, I don't want to malign generics because we are also encouraging physicians to write prescriptions for generics, and yet at the same time if we are not inspecting these plants properly we end up with causing more problems. So, does FDA have any positions they recommend then in terms of what other branches of government, Medicare and Medicaid should be doing? Are they requiring doctors to write prescriptions for generics while at the same time we can't assure that those are pure? Ms. Woodcock. Well, I would point out that Heparin was not a generic drug. There were various versions of Heparin on the market, but that was not a generic drug. This is not necessarily a generic drug problem. This is pervasive drug quality problem, and we don't have evidence that generics particularly have additional quality problems over innovator drugs. So I think physicians should write for generic drugs with confidence. But we do need to make sure we manage the supply chains, that we and mainly the companies have the systems in place to make sure that they maintain the quality of their drugs that are sold in the United States. Mr. Murphy. I appreciate you pointing that out about generics. That is a very important fact. We don't want people to be worried about that. It has to do with the content that comes over. You had mentioned that plants can be inspected about once every 9 years. The GAO says it is more like every 13 years or so. Plus isn't it true that when you are inspecting a plant in the United States, you can just show up on a surprise visit if you wish? Ms. Woodcock. Correct. Mr. Murphy. And the chances of surprising someone in China is slim and none? Ms. Woodcock. Right. Mr. Murphy. So they have a chance to change that. And so on this globalization of drug manufacturing and supplies, are there caveats that the FDA is saying then to manufacturers in the U.S. that even though you cannot inspect this, other standards you are asking them to handle on their own with this as well? Ms. Woodcock. Yes. Basically we feel that the ultimate responsibility lies with the manufacturer. We are not their quality assurance group. We are auditors to make sure that they are obeying the rules and that they are maintaining quality, and we audit all around to make sure they do that. There is also testing, which isn't everything, but having good analytical tests for potency, sterility and making sure the manufacturers conduct those tests, and for impurities, can go a long way to help ensure the safety of the drug supply. Mr. Murphy. Thank you, Mr. Chairman. Mr. Pitts. The chair thanks the gentleman and recognizes the gentleman from Michigan, Mr. Rogers, for 5 minutes. Mr. Rogers. Thank you, Mr. Chairman. Thank you, Doctor, for being here. Is venture capital important in the development of the next generation of pharmaceuticals, do you believe? Ms. Woodcock. Yes, venture capital is very important to a segment of the drug development industry, the smaller and arguably more innovative side of the industry. Mr. Rogers. They are targeting special treatments for cancer or for sepsis or all of those things, right? That is where the venture capital kind of flows to those innovative--so you are arguing it an important part hopefully of the next cure, we would hope? Ms. Woodcock. Certainly for innovation. The biotech sector depends on venture capital. Mr. Rogers. I happened to be reviewing the testimony of someone on the panel, Jonathan Leff. I am just going to read some things from here just to get your perspective on this. ``During 2010 and 2011 to date, first time fundings of life sciences ventures, a key leading indicator of the health of the innovation ecosystem, has decreased by more than 50 percent due to prior years.'' That is a problem, isn't it? Ms. Woodcock. Yes. Mr. Rogers. What would you attribute that problem to? Ms. Woodcock. The problem is due to the failure rate and the fact that--again, I am not an economist, but what I have been told is that these firms are not successful enough to merit the return on investment, and also there is a longer term development cycle, that venture capital prefers a shorter return, and so biotech has become less attractive. Mr. Rogers. So it is all the investors that are pulling out of the market. It wouldn't have anything to do--here is his assessment. ``The FDA's shift in recent years to an increasingly cautious risk-averse posture towards new drug approvals has the unintended consequence of reducing investment in life sciences innovation due to the significant additional time,'' which you mentioned, ``cost and uncertainty it has added to the drug development process.'' True? Ms. Woodcock. Well, there is uncertainty in the drug development process, and that is the main problem. To lay it all at the feet of the FDA I don't think is correct. McKenzie has recently done a study where they looked at failures in Phase III development, which is clinical--the last stage of clinical trials, and of products that failed there, fifty percent failed because they had no benefit compared to placebo. It is really hard to attribute that to the FDA. Mr. Rogers. I certainly understand. But if the FDA doesn't recognize it has a problem, we will never get any segment of that fixed? Ms. Woodcock. I recognize it. As I said in my oral testimony, I think there is a crisis in the industry, and it is pervasive and it is very concerning. Mr. Rogers. What would be your recommendation for Congress to try to help us through that particular process? Can you clearly say that the added time and bureaucracy and investment is gaining--it is worth the sacrifice of losing innovation and attracting capital? Is it worth it? Ms. Woodcock. We feel that the scientific challenges are the problem, not the regulatory challenges. So I would disagree with Mr. Leff on this. And our data shows that we have a very high rate of first cycle approval. So it is hard to lay this at FDA's feet. I was hesitating in responding to you because I have a whole list of prescriptions for this problem that I have been promulgating for some time, and I would be happy to share those with you outside of this venue, because they are fairly extensive. Mr. Rogers. I would be delighted. With your permission, I would receive that at your earliest convenience. I think that would be helpful. The lines in the sand are hard things, and when you look at the real decrease in investment, to say that the FDA isn't a part of that problem is a little concerning. Let me give you some other statistics here I find shocking. The venture capital funds raised have decreased 25 percent in 2010 just over 2009, and that is the third consecutive year of decline. The share of venture capital invested in biotechnology declined from 18 percent in 2009 to 12 percent in 2010. From 2008 to 2010, investment in U.S. Life sciences companies declined by $2 billion. That is significant. And I agree with you, it is a crisis that we are going to have to deal with. As a cancer survivor myself, I hope somebody is willing to put up the capital to go through the process, and I want the FDA to understand that there are risks involved and they should be part of the process to help quickly determine the efficacy of that particular drug. I am concerned that the risk aversion has crept into the FDA to a point that it is costing us innovation in the United States, and to me that is an unacceptable outcome. Do you think there would be any value in having a category of drug, and I heard the discussion earlier, you know, if I am sitting with my oncologist and my oncologist tells me that this is the particular drug that I have seen work, it has saved someone's life, it has added years to their life, but the FDA says I can't give it to you even if I explain all the risks involved, is there a better way to do that? Ms. Woodcock. Well, I don't think the FDA--that is the FDA's posture, that people can't give drugs to patients. As I said earlier---- Mr. Rogers. Well, if you take it off the market, it clearly is. Ms. Woodcock. Are you talking about Avastin? Mr. Rogers. Yes. As an example. I just used that as an example. Ms. Woodcock. Avastin is on the market for other indications and will remain on the market. Mr. Rogers. I don't want to debate if you feel that is the right decision. But shouldn't there be the opportunity--I tell you that, because many a Member will run into a constituent who will fly out of the country to get access to a drug because they have made the conclusion that their life is at a point where they are willing to take that risk. Ms. Woodcock. Right. Mr. Rogers. Is there some value in that in the United States? Do we have to force people to go to Mexico to do this? Ms. Woodcock. We don't stand between people getting investigational drugs if they have no other options, and we passed regulations about 18 months ago that provide a broad range of ways to access totally investigational drugs, especially for people who have exhausted other types of therapies. So we agree that people have a right to take substantial risk. Mr. Rogers. At their own risk. Ms. Woodcock. Yes. Mr. Rogers. I would love to work with you on the expansion of that. I think there have been some problems in the past and currently that I think we can, working together, solve this problem for literally thousands and thousands of people who are at a pretty emotional place in their life and are willing to take some risks. With that, I yield back. Mr. Pitts. The chair thanks the gentleman. That concludes our first panel. Dr. Woodcock, thank you very much for your testimony, for your answers to our questions. At this point, we will call the second panel. I think we will take 5 minutes here just to check the mikes and then we will reconvene. [Recess.] Mr. Pitts. I think we are ready to reconvene. Our second panel has a number of witnesses, and I will introduce them and ask them to testify in this order. Paul Hastings is the President and Chief Executive Officer of OncoMed Pharmaceuticals. Jonathan Leff is the Managing Director of Warburg Pincus. Mark Boutin is the Executive Vice President and Chief Operating Officer of the National Health Council. Dr. Ellen Sigal is the Chair and Founder of Friends of Cancer Research. Lastly, Allan Coukell is the Director of Medical Programs of the Pew Health Group of the Pew Charitable Trust. Your written testimony will be made a part of the official record. We ask that you summarize your opening statements in 5 minutes. Mr. Hastings, you may begin. STATEMENTS OF PAUL J. HASTINGS, PRESIDENT AND CHIEF EXECUTIVE OFFICER, ONCOMED PHARMACEUTICALS, INC., ON BEHALF OF BIOTECHNOLOGY INDUSTRY ORGANIZATION; JONATHAN S. LEFF, MANAGING DIRECTOR, WARBURG PINCUS, LLC; MARC BOUTIN, EXECUTIVE VICE PRESIDENT AND CHIEF OPERATING OFFICER, NATIONAL HEALTH COUNCIL; ELLEN V. SIGAL, CHAIRPERSON AND FOUNDER, FRIENDS OF CANCER RESEARCH; AND ALLAN COUKELL, DIRECTOR OF MEDICAL PROGRAMS, PEW HEALTH GROUP, THE PEW CHARITABLE TRUSTS STATEMENT OF PAUL J. HASTINGS Mr. Hastings. Thank you. Chairman Pitts, Ranking Member Pallone, members of the committee, my name is Paul Hastings. I am the President and Chief Executive Officer of OncoMed Pharmaceuticals. I am here testifying on behalf of the Biotech Industry Organization's 1,100 members, where I serve as Vice Chairman of the Emerging Company Section; that would be small companies. I also chair the Bay Area Life Sciences Association, and I am a member of the board of the California Health Care Institute. All of these organizations represent innovative life science companies. I have over 25 years of experience in the biotechnology and pharmaceutical industry. My current company, OncoMed Pharmaceuticals, is developing molecules based on new understandings of how tumors grow and spread. Specifically, we are trying to block biological pathways critical for the survival of tumor initiating cells. These cells are more resistant to current therapies and promote the growth of cancerous tumors. Thus, our products offer real advancement in the treatment of cancer. We presently have three products in Phase I and Phase I-A clinical trials after being in existence for 6 years. Companies like mine are generating many new therapies to treat patients suffering from a myriad of unmet medical needs. Of the 172 scientifically novel and orphan drugs approved from 1998 to 2007, 52 percent of them were discovered or developed by biotechnology companies. We offer tremendous hope to patients, with over 3,700 new biotherapeutics in development. Biotechnology is an American success story. Our life science sector accounts for over 7 million in direct and related jobs. We create high-paying jobs in our companies and support employment and provide vital revenue for our universities and medical centers through the clinical trials we conduct, thus employing people in those important State and local universities and medical centers. We have a national imperative to foster the development of innovative treatments and therapies. By 2030, almost one out of every five Americans will be 65 years or older, which means dramatically increased costs associated with treating chronic disease. Innovative medicines can help offset these costs by preventing or delaying the need for other costly services such as emergency room visits and hospitalizations. If you just simply reduce cancer deaths by 10 percent, that is equal to $4 trillion in economic value. Our position as global leadership is a position we can no longer presume to keep. We face international threats, such as India and China and the European Union increasing funding and incentives for biotech companies, while at the same time investment in the U.S. has decreased markedly. To encourage innovation and maintain U.S. leadership, we must have an FDA that is empowered and able to effectively and consistently review breakthrough treatments and therapies. There are several troubling trends that threaten to severely hamper our ability to innovate. For example, only half of the products submitted to the FDA are approved on the first submission. From the average of the previous PDUFA rounds of 2003 to 2007 to today, drug and biologic approval times have increased 28 percent, and between 1999 and 2005 the average length of clinical trials grew by 70 percent. Regulatory uncertainty deters future venture investment in biotechnology companies. This results in longer time for development, not time for approval once drugs are submitted, longer time for development when you start the development process in Phase I; lower investment, fewer cures for patients, and not as many life science jobs. It is important to maintain a balanced and consistent regulatory system. To that end, among BIO's top priorities throughout the PDUFA technical discussions was to promote innovation by fostering scientist-to-scientist dialogue between FDA and sponsors concerning high priority rate limiting scientific issues that arise during drug development. We are pleased that FDA agreed to adopt a new policy that timely interactive communication with sponsors during the drug development is a core activity to help achieve the agency's mission. BIO believes that PDUFA should be reauthorized in a timely and expeditious manner. However, additionally, last week during the BIO international convention, we unveiled a package of policy proposals entitled Unleashing the Promise of Biotechnology: Advancing American Innovation to Cure Disease and Save Lives. This is a BIO initiative, with the thought in mind to come with you with not complaints but solutions. The FDA policy recommendations described in my written testimony are designed to ensure a clear and effective pathway for turning ideas into realities that will benefit patients and improve public health. The proposals are focused on creating a modern, forward looking FDA and creating more effective clinical research and development processes. Some of the highlights of our proposals include updating the FDA mission statement to reflect its role in advancing medical innovation; providing FDA with the management, budgetary and advisory authorities reflective of its role in regulating a quarter of our country's GDP; providing FDA with authorities, expertise, implementation mechanisms to ensure the development of forward-thinking strategies and implementation of modern regulatory science into their review practice; expanding and improving the accelerated approval pathway into a progressive approval mechanism for innovative products for unmet medical needs that would also serve to ensure a risk- benefit analysis that incorporates the safety and needs of patients in the real world. Lastly, proposals to further empower the FDA to utilize a weight of the evidence approach and ensure that the FDA communicates to sponsors in clear terms why risk was determined to outweigh benefits and why other agency authorities, such as REMS, are insufficient. Thank you for the opportunity to share with you our thoughts today. [The prepared statement of Mr. Hastings follows:] [GRAPHIC] [TIFF OMITTED] T2917.034 [GRAPHIC] [TIFF OMITTED] T2917.035 [GRAPHIC] [TIFF OMITTED] T2917.036 [GRAPHIC] [TIFF OMITTED] T2917.037 [GRAPHIC] [TIFF OMITTED] T2917.038 [GRAPHIC] [TIFF OMITTED] T2917.039 [GRAPHIC] [TIFF OMITTED] T2917.040 [GRAPHIC] [TIFF OMITTED] T2917.041 [GRAPHIC] [TIFF OMITTED] T2917.042 [GRAPHIC] [TIFF OMITTED] T2917.043 [GRAPHIC] [TIFF OMITTED] T2917.044 [GRAPHIC] [TIFF OMITTED] T2917.045 [GRAPHIC] [TIFF OMITTED] T2917.046 Mr. Pitts. The chair thanks the gentleman. Mr. Leff, you are recognized for 5 minutes. STATEMENT OF JONATHAN S. LEFF Mr. Leff. Thank you. Chairman Pitts, Ranking Member Pallone, and members of the committee, my name is Jonathan Leff. I am a managing director at Warburg Pincus, where I lead the firm's investment efforts in biotechnology and pharmaceuticals. I have more than 15 years of experience as a life sciences venture investor and have served on the boards of and helped build more than 15 small entrepreneurial companies involved in developing novel therapies for a range of diseases, companies not unlike the one that Mr. Hastings described. It is my privilege to be here today. Venture capital provides the essential fuel for medical innovation by funding the development of novel therapies, an endeavor that requires hundreds of millions of dollars over many years or even decades. Venture capital has been a primary source of this vital risk capital, has funded the development of an entire generation of important new medicines, and has financed and helped build almost every successful biotechnology company in the U.S., creating well over 1 million high quality jobs. Today, however, the U.S. medical innovation ecosystem is in jeopardy. Life sciences venture capital is experiencing an alarming decline. The primary reason is that the cost, time and risk involved in developing new drugs and biologics have increased to unsustainable levels. As a result, vital risk capital is being diverted to other industries and to other countries. At a time when medical research is exploding with potential, many scientific discoveries are not being developed into new medicines due to lack of investment capital. While many factors have contributed to the escalating cost, time and risk of drug development, a changing regulatory environment at the FDA is the most significant. In the early 1990s, Congress and the FDA worked together to shape a new drug approval system designed to balance the goal of ensuring drug safety with the desire to speed new therapies to seriously ill patients. As a result of this balanced regulatory environment, for example, HIV is no longer a death sentence, cancer patients have access to many dozens of important new medicines, and the U.S. has established itself as the world's leader in life sciences innovation. By the middle of the last decade, however, the political backdrop and public consensus that made all of this possible had changed. Following the safety issues with Vioxx, the public discourse began to heavily emphasize drug safety. Far from being congratulated for speeding new treatments to sick patients or for advancing medical innovation, FDA has instead come under heavy criticism for failing to do enough to ensure patient safety. Naturally, FDA officials have responded to this changing environment, including congressional hearings and media attention, and have shifted to a more cautious, risk averse posture in the new drug approval process, emphasizing the potential risks of new treatments more than their benefits to patients. My written testimony provides examples of how this shift has become evident. Without question, protecting patients from harm is an essential element of what the public expects from the FDA. But so too is enabling the timely development and availability of new therapies. Finding the right balance is the central challenge of the new drug approval process. However, I want to emphasize that the way this balance is struck by regulators and by policymakers has tremendously important implications for U.S. leadership in medical innovation. FDA's shift in recent years to an increasingly cautious posture toward drug approvals has had the unintended consequence of reducing investments to life sciences innovation due to the significant additional time, cost and uncertainty it has added to the drug development process. In the face of new hurdles to FDA approval, investors are moving away from critical areas, including cancer, diabetes, rare diseases and many others. I believe these problems are fixable if we act now. Twenty years ago, U.S. policymakers and the FDA rose to the challenge. We have the opportunity to do the same today. My recommendations are as follows: Strengthen FDA's mission statement to reflect the importance of innovation; expand the accelerated approval pathway into a progressive approval system for new drugs that offer a significant advance; empower FDA to weigh all evidence in the context of the disease being treated in assessing benefit versus risk in new drug approvals; fully detail the FDA's benefit-risk calculus when denying or delaying approval in favor of collecting more data; and, finally, ensure that FDA is provided with the resources that it needs to accomplish its mission. I look forward to working with the committee to reinvigorate and strengthen U.S. leadership in medical innovation. Thank you. [The prepared statement of Mr. Leff follows:] [GRAPHIC] [TIFF OMITTED] T2917.047 [GRAPHIC] [TIFF OMITTED] T2917.048 [GRAPHIC] [TIFF OMITTED] T2917.049 [GRAPHIC] [TIFF OMITTED] T2917.050 [GRAPHIC] [TIFF OMITTED] T2917.051 [GRAPHIC] [TIFF OMITTED] T2917.052 [GRAPHIC] [TIFF OMITTED] T2917.053 [GRAPHIC] [TIFF OMITTED] T2917.054 [GRAPHIC] [TIFF OMITTED] T2917.055 [GRAPHIC] [TIFF OMITTED] T2917.056 [GRAPHIC] [TIFF OMITTED] T2917.057 [GRAPHIC] [TIFF OMITTED] T2917.058 [GRAPHIC] [TIFF OMITTED] T2917.059 [GRAPHIC] [TIFF OMITTED] T2917.060 [GRAPHIC] [TIFF OMITTED] T2917.061 Mr. Pitts. The chair thanks the gentleman, and recognizes Mr. Boutin for 5 minutes for an opening statement. STATEMENT OF MARC BOUTIN Mr. Boutin. Thank you, Mr. Chairman, Ranking Member Pallone, and distinguished members of the committee. My name is Mark Boutin, and I am the Executive Vice President and Chief Operating Officer at the National Health Council, which represents approximately 133 million people with chronic diseases and disabilities. Our membership includes large patient advocacy organizations like the American Cancer Society, the American Heart Association, as well as smaller organizations like the Alpha One Foundation and the Children's Foundation. We provide a united voice for people with chronic diseases and disabilities. Our membership also includes organizations such as the American Academy of Cardiology, nonprofits with interests in health, including family care giving organizations, and business and industry. Our governance is controlled by the patient advocacy organizations, and we represent patients, not consumers. I make that point because often patients and consumers are confused. While we have a lot in common, we are at opposite ends of the same spectrum. We define patients as people with chronic diseases and disabilities. They are people who will use the health care system to manage their daily lives. They will use the health care system until they die. Consumers use the health care system on an ad hoc basis, often for acute instances. An easy way to put your arms around it is imagine that you have mild hay fever. It acts up in spring. There are many options to address hay fever, over-the- counter prescriptions. But I can tell you if a new product comes to market and it has serious side effects, perhaps it causes severe headaches, rashes, diarrhea, vomiting, you are not going to be willing to take a risk on that new medicine. But if you discover that you are having intestinal problems, you go to your doctor after putting it off for some time and you are diagnosed with pancreatic cancer and you are told you have 11 months to live, your willingness to take a product that might extend your life by 6 months will dramatically increase. You might be quite happy to take that same product that causes the rash, severe headaches, diarrhea, vomiting. It doesn't change your tolerance for risk for the hay fever medicine. Benefit-risk is an incredibly complex issue and one of the things I would like to address today. As has already been referred to earlier, the patient advocacy community actually chained themselves to the fence at FDA and NIH nearly 20 years ago asking for significant change, and as a result of that, they went to the FDA and said, let's be allowed to have early access to treatments. And the FDA appropriately said, no, we are not going to allow you to have access to those treatments. We don't know what the risks of them are. The patient community said, you know what? I am going to be dead in 2 years, I am willing to accept that risk. And the FDA responded and Congress responded with the first iteration of PDUFA. As a result, we have seen dramatic improvements in terms of early access to new treatments and the development of new treatments, and we in the patient community have been very pleased with the success of these products. Unfortunately, the patient communities, somewhat naively, thought we were done. We are relatively new to advocacy. We really only started about 25 years ago. We actually stepped back to a large extent from the FDA and the environment shifted, and what we have seen is significant change. We are back at the table now saying that we need to look at these issues in different ways. What I would like to do is address two interrelated issues, the first being benefit-risk, the second being conflict of interest. As I said, benefit-risk is a complex issue. The FDA is charged with looking at benefit-risk from a population-based model. But as we know, benefit-risk is very much an individual decision. It is very personalized to the individual person and their family caregivers. Take for example Mark Stecker, who is somebody that about 7 years ago was walking in Manhattan and realized he had a limp. Shortly thereafter he was diagnosed with MS. He is now confined to a wheelchair, and he runs a blog, and he is very articulate about saying that he is very interested in assuming far greater risk than he is currently allowed. I would say to you, many people in the disability and disease community feel the same way. While we had great success for HIV and AIDS, to some extent cancer and to a lesser extent heart disease, there are many conditions, from rare diseases to larger conditions like Alzheimer's, MS and other neurologic conditions without effective treatments, with many people willing to accept risk that they are often not allowed to. As I said, this is complex, and risk determinations can vary from condition to condition. Somebody with Alzheimer's is probably more likely to take a risk than somebody with heart disease. It can change even within an individual. If you think about somebody with breast cancer that is in their late twenties and they have two children, their willingness to take a risk that might extend their life long enough to see their children grow up and get married, because it is very pronounced. But you could have another woman in her eighties with the same diagnosis who might choose a different product that is going to allow her to have better quality and perhaps less longevity. At this point in time, it is important to recognize that there is no Federal regulatory body anywhere in the world that has identified benefit-risk or crafted a clear framework for benefit-risk. As part of the PDUFA negotiation, the stakeholder community was involved, and this was a huge priority for the patient community, and we were able to work with the FDA and industry to insert a benefit-risk analysis into the agreement. This will allow for a great deal of consistency, transparency and effective communication. It will allow for the benefits to be more clearly defined and it will allow for contacts and credibility. I apologize for running over my time. Thank you. [The prepared statement of Mr. Boutin follows:] [GRAPHIC] [TIFF OMITTED] T2917.062 [GRAPHIC] [TIFF OMITTED] T2917.063 [GRAPHIC] [TIFF OMITTED] T2917.064 [GRAPHIC] [TIFF OMITTED] T2917.065 [GRAPHIC] [TIFF OMITTED] T2917.066 [GRAPHIC] [TIFF OMITTED] T2917.067 [GRAPHIC] [TIFF OMITTED] T2917.068 [GRAPHIC] [TIFF OMITTED] T2917.069 [GRAPHIC] [TIFF OMITTED] T2917.070 [GRAPHIC] [TIFF OMITTED] T2917.071 Mr. Pitts. The chair thanks the gentleman, and recognizes Dr. Sigal for 5 minutes. STATEMENT OF ELLEN V. SIGAL Ms. Sigal. Good afternoon, Chairman Pitts, Ranking Member Pallone, and all members. It is a great honor for me to testify today. My name is Ellen Sigal. I am chair of Friends of Cancer Research. Friends of Cancer Research is a Washington-based think tank. We publish. We are involved with the American Cancer Society, professional societies, patient groups, advocates. Our sole mission is really the integration of science for better treatment for patients. This is very personal for me, as it is for all of you. Friends started 15 years ago when I lost my 40-year-old sister, leaving a 4-year-old child. Since then, my mother died of pancreatic cancer, my father died of prostate cancer, my husband has cancer, and there is no one that we all don't know that isn't impacted. So this mission is quite personal for me and for all of you. My testimony today is intended to give a perspective on what can be done. First of all, the urgency of getting new life-saving treatments to patients in the safest and quickest possible way; the importance of maintaining our global competitiveness; and finally to realize the full potential of biomedical research and the role that all sectors play. None of these things can be accomplished without a fully resourced and scientifically vigorous FDA. For many years we have been hearing about the slowness of FDA and particularly in oncology, so the agency has been portrayed by many critics as slow and inefficient compared to other countries. The criticism is particularly concerning in the field of cancer, where severely ill patients have few effective options. A new Friends of Cancer Research study published in Health Affairs revealed that FDA is approving anti-cancer drugs much faster than its overseas counterpart, the European Medicines Agency. What is important is the standard is high. It is the gold standard on both. Of its findings, our study revealed that FDA not only approved more cancer drugs than Europe, but they did so at a significantly faster rate. FDA approved average drugs in 182 days, while EMA averaged 350 days. Access to new medications 5 \1/2\ months sooner has undoubtedly improved the lives of 1.5 million Americans diagnosed with cancer every year. While we praise this and we think this is very important, this cannot be accomplished nor sustained without appropriations needed to continue this effort. I have very specific recommendations that are in my testimony, and I would like to talk about a few of them. First and foremost, FDA has to have the scientific tools, the regulatory science programs better to enable them to make these very complicated decisions. Whether it is adaptive trial design, validation of biomarkers, it is urgent that they have the resources to really have this. We believe very strongly and support the continuance of accelerated approval process. Ten of the 32 new oncology products in our study utilized this mechanism. We also are recommending expedited development programs to address challenges to the current multi-phase sequential development process. This could be particularly important to ensure scientific rigor for targeted therapies. We want to ensure that FDA has the highest quality access to the best expertise possible in making informed decisions, and we believe patients have a very important role at that table and that role has to be accelerated. A weakened, underfunded FDA will cause companies to take research overseas, creating a loss of jobs and billions of dollars in investment, it will threaten our standing as global leader, and, most importantly, it will delay getting potentially lifesaving treatment to patients battling disease and illness. The role of the Food and Drug Administration as a component of medical innovation is critical, but successful innovation does not solely include the FDA. Our data indicates that the end stage review is on average half the duration of the FDA U.S. and EMA. While this indeed translates to American cancer patients gaining access to new drugs, it does not address the fundamental challenges to advancing health innovation that are currently facing our society. In order to resolve the larger problem, all of the sectors represented at this hearing today and several of those that are not must at all times set aside the individual interests and work towards the common goal of improving the health of the country, both economic and personal, through innovation. As patients, we all have been and we all should demand it. The people will all work on behalf of the deserved. We are asking that everyone work together towards these goals. Thank you. [The prepared statement of Ms. Sigal follows:] [GRAPHIC] [TIFF OMITTED] T2917.072 [GRAPHIC] [TIFF OMITTED] T2917.073 [GRAPHIC] [TIFF OMITTED] T2917.074 [GRAPHIC] [TIFF OMITTED] T2917.075 [GRAPHIC] [TIFF OMITTED] T2917.076 Mr. Pitts. The chair thanks the gentlelady, and now recognizes Mr. Coukell for 5 minutes for an opening statement. STATEMENT OF ALLAN COUKELL Mr. Coukell. Mr. Chairman, Ranking Member Pallone, members of the subcommittee, thank you for the opportunity to present testimony. My name is Allan Coukell. I am a pharmacist by training and Director of Medical Programs in the Pew Health Group, whose mission is to improve the health of all Americans through research and critical analysis. Pew's work addresses a range of FDA-related issues, but my focus today is the safety and security of the pharmaceutical supply chain. Next week we will release a report entitled ``After Heparin: Protecting Consumers from the Risks of Substandard and Counterfeit Drugs.'' Our research for that report included dozens of interviews with industry and regulatory experts and was informed by a recent public meeting that brought together pharmaceutical manufacturers, distributors, pharmacies, the FDA, State regulators and other analysts and stakeholders. The meeting heard that while the vast majority of drugs in our pharmacies and medicine cabinets are not counterfeit or adulterated, drug manufacturing has changed dramatically in recent years. It has become globalized and increasingly outsourced, and this creates new risks, risks dramatically illustrated not long ago with the intentional adulteration of the blood thinning drug Heparin. In 2007, health officials began to receive the first of what would ultimately be more than 500 reports of patients who experienced unusual adverse events, some of them fatal, after receiving this drug. The problem was traced to a contaminant, a substance introduced in place of the pure drug, and this occurred not in the premises of the U.S. manufacturer, but in China where the drug's raw ingredient was sourced from a complex network of suppliers. The evidence suggests that the adulterant was introduced deliberately on a large scale and for economic gain. Whoever made it must have known that the substance wouldn't be detected by the standard tests. By one estimate, the crime netted more than $1 million in profit. Later investigations pointed to other failures that underlined the need for systemic improvement. In particular, the manufacture did not audit its supplier over several years. The FDA approved the Chinese plant without an inspection, partly because agency databases confused two different facilities. Inspectors later found manufacturing quality issues, including poor control of incoming materials. And neither the FDA nor the manufacturer was ever able to gain complete access to that upstream supply chain. The incident represents a clear breach of the U.S. drug supply, and to this date no one in any country has been held accountable nor has Congress acted to update the statutes that govern drug manufacturing. What we heard at our meeting from a variety of experts was that without changes to the system, another such event is inevitable, not if, but when. The number of drugs and ingredients made at non-U.S. sites doubled over the past decade. About 40 percent of our finished drugs and 80 percent of their active ingredients now come from overseas, often from developing countries. Current law requires FDA to inspect every 2 years here in the U.S., but is silent on the frequency of foreign inspections and the FDA lacks the resources to do regular foreign inspections. When manufacturing shifts to low cost environments with reduced oversight, consumers are at risk, from the deliberate acts and also from failures to meet quality standards. Our report reviews some other recent examples, including the problem of so-called show shadow factories, where drugs are coming from a hidden source instead of the official factory. We discussed cases in which manufacturers falsified or concealed records, and we note the risk of U.S. patients receiving counterfeit or stolen drugs that penetrate our domestic distribution system. Let me give you one more example, a substance called DEG that has been linked to numerous mass poisonings around the world. Five years ago, this sweet-tasting liquid was mistakenly used to make cough syrup, killing dozens. The syrup had been labeled as something else. It had passed through a series of brokers in China and in Europe, each relabling it presumably without testing. Many of those who died were children. This occurred outside the U.S., but 70 years ago this same substance killed more than 100 Americans and led Congress to pass the Food, Drug and Cosmetic Act. So recently there have been important steps by the FDA and by individual companies to tighten the supply chain. Nevertheless, we must update the act for the 21st century. Pew advocates a number of key reforms, including measures to ensure that manufacturers themselves better assess risk and ensure safety and steps to ensure they are held accountable; increased inspections overseas and new enforcement tools for the FDA, including the ability to order drug recalls; and improved oversight of drug distribution, including national standards for wholesalers and assistance to track and verify the authenticity of drugs. I will conclude just briefly with a recent poll, a poll we commissioned last year among likely voters, that showed Americans are concerned about this issue, and across the political spectrum they overwhelmingly, upwards of 80 and 90 percent, favor many of the provisions I have outlined. This committee has long taken a bipartisan interest in the safety of the drug supply. The American public supports those efforts, and we should not await another tragedy. Thank you, and I welcome your questions. [The prepared statement of Mr. Coukell follows:] [GRAPHIC] [TIFF OMITTED] T2917.077 [GRAPHIC] [TIFF OMITTED] T2917.078 [GRAPHIC] [TIFF OMITTED] T2917.079 [GRAPHIC] [TIFF OMITTED] T2917.080 [GRAPHIC] [TIFF OMITTED] T2917.081 [GRAPHIC] [TIFF OMITTED] T2917.082 [GRAPHIC] [TIFF OMITTED] T2917.083 [GRAPHIC] [TIFF OMITTED] T2917.084 Mr. Pitts. The chair thanks the gentleman and thanks the panel for the testimony. We will now begin questioning, and I will recognize myself for 5 minutes for that purpose. First of all, Mr. Hastings, I have had the opportunity to talk to many small and mid-sized American biotech companies, and they are struggling right now partly because of increasing review times at FDA and the lack of predictability at FDA. Have you experienced these problems or do you know a company who has, and what issues are biotech companies facing today related to FDA? Mr. Hastings. We work very--is this on? No. There we go. Sorry about that. Whenever there are regulatory uncertainties, there are delays. A big piece of data that is missing today is not the speed of approval once an NDA is filed, but the speed to which we can enter a drug into the clinic, file an IND, get it through Phase I, get it into Phase II. Many of us who are lucky enough to get it into Phase III would be happy with approval times that are faster and more expedient than other countries. That would be great. But there is a whole process that occurs before the drug even is filed for an NDA, and I think it is important for us to work with the FDA, as we have. As I mentioned, the biotech industry's focus here is on streamlining the whole process, not just the approval process once the NDA is filed. Mr. Pitts. Mr. Leff, would you like to comment on that? Mr. Leff. Sure. Thank you, Mr. Chairman, I would be happy to. I think the central issue, the central impact that FDA is having on investors in medical innovation is, as I said in my statement, the increase in the time, the cost, and the risk of development. So it is not review times per se, although obviously we all want fast and efficient review times. It is the requirements that FDA is increasingly imposing for developers of drugs to move their drugs through clinical trials and get them in front of FDA. So when Dr. Woodcock made the observation that FDA is having a problem approving more drugs because they are not seeing more drugs, they are seeing fewer drugs submitted than in the past, I think that is absolutely right. The reason FDA is seeing fewer drugs submitted than in the past is because people like me and hundreds of other people like me making investment decisions on drugs that are in development or discoveries that are being turned into drugs are increasingly deciding that the cost, time and risk have become too high, and that is a function of the risk averse decisionmaking that has increased at FDA over the past decade. Mr. Pitts. Mr. Hastings, how many jobs does the bioscience sector account for, both direct and indirect? Mr. Hastings. I think I mentioned 7 million jobs indirectly and directly. Mr. Pitts. Seven million total. What else can we do in the FDA space to help create jobs? How would fixing the issues at FDA help these companies create jobs? Mr. Hastings. Mr. Chairman, I believe that the way to create jobs is to foster innovation, not at the expense of safety or efficacy. One of the proposals which is to make innovation a part of the mission statement, which, by the way, the European Union has in their mission statement, and then hold people accountable for innovation. You know, innovation could be when somebody is going through the process of--I will give a very practical example. I am running a startup company and I file an IND and I get my drug into Phase I. In the middle of my Phase I trial, there is an issue. Any kind of issue could come up in Phase I. The way the system is set up is I can pick up my phone or my regulatory person can pick up the phone and call the FDA. And the FDA are bound by these guidelines, by the way. The phone call takes place. It needs to be followed up by a letter, which comes usually 30 days later. Then you have 30 days to respond to that letter. Then they have 30 days to respond to that letter. Now, in that whole process, which in my mind could be handled in a phone call, I spent as a startup biotech CEO $4 million a month on the burn of the company while the letter writing campaign was going back and forth. This is not the FDA's fault. These guidelines are guidelines that have been put in place, and I think they should be looked at as, you know, how can we streamline communication. Again, not once the NDA is filed, but how do we help companies innovate by making the process smoother in areas which are not going to create more risk? I think this would be a major. So if that occurs, I don't have to go to my venture capitalist and say I am writing a letter now and $4 million of burn is looking at us right down the face. He hears that $4 million and says if I could invest that $4 million in Facebook, I could get a return in a month. You are going to burn that. I am going to need to give you--now, for me I need $1 billion to develop a drug, right? So that $4 million, which is huge in the early stages of a drug company's evolution, is just a tiny portion of what it is going to take. So each dollar is very, very important. So for innovation and streamlining, making processes and helping the FDA, by the way, make processes that are less bureaucratic, providing them with the staff they need to actually answer the phone calls, which is something we have been working on together, would be very helpful. Mr. Pitts. The chair thanks the gentleman. My time has expired, and the chair recognizes the ranking member, Mr. Pallone, for 5 minutes. Mr. Pallone. Thank you, Mr. Chairman. I am going to start with Mr. Hastings also. BIO recently released policy recommendations contained in the document ``Unleashing the Promise of Biotechnology: Advancing American Innovation to Cure Disease and Save Lives.'' I appreciate the need for the kinds of proposals listed under the heading of Advancing Regulatory Science and Innovation. But I wanted to focus on one as an example, the need to enhance FDA's access to external scientific and medical expertise. The FDA has repeatedly cited the need to make improvements in the area of regulatory science, and as the BIO policy document mentions, FDA has struggled to keep up with the rapid pace of scientific and medical knowledge techniques and technology. And you know FDA launched a major regulatory science initiative designed to build on the achievements of programs like the critical path initiative. The other proposals in that section also seem to make a lot of sense to me. But my problem is that each of these concepts that you mentioned or that, I should say, the document mentions would demand a significant infusion of resources if there is any hope for the FDA to implement them. That is my opinion. I just wanted to ask you if you agree with that, that we need more resources to do these kind of things? Mr. Hastings. I think respectfully---- Mr. Pallone. I think you lost the mike. The reason I am asking you this is--go ahead. I am sorry. Mr. Hastings. Somebody up there where you folks are a few minutes ago had an overreaction to an issue with a union, right? So I think if we can all work together to look at ways to prioritize. First of all, there is no question that our industry supports the FDA being adequately staffed. We actually had an initiative a few years ago to help them get staffed. So we would be all for helping them get staffed. But we also understand there are budget crises under way right now. So I would submit, running a business, and having run many businesses, private and public businesses, that there are always ways to reallocate resources to do things. External advisory boards are external people. You pay them when they walk through the door. When they leave, you stop paying them. That is a much more efficient use of capital than head count. So if there are opportunities to use external advisers to help keep regulatory science moving. In the case of FDA, by the way, they have very few regulatory science employees. They would like to have more. Again, we are working on this initiative. So there are many ways to do this. Mr. Pallone. The only problem that I have though, now we have this FDA funding bill that the House Republicans just passed, and that guts the FDA's funding by $570 million. It is a cut of 21 percent from the administration's request. So obviously I think there should be more resources. But if this goes through, we will have 21 percent less than what the administration is requesting. How are we going to implement these types of things that are in this BIO document if we make cuts? It is one thing to add. But what about now if they cut 21 percent? Mr. Hastings. Again, I would argue that one could look at reallocation, and one could also look at the risk-benefit of where one invests one's money. Mr. Pallone. All right. I know that you are part of this-- or I should say your organization is part of this alliance for a stronger FDA whose mission is to get increased resources for FDA. So, again, I think you can always find more efficiencies, but I think it is going to be very difficult to do any of these new innovations if we see a 21 percent cut, and I think that is why the Alliance for a Stronger FDA is trying to increase resources. Mr. Hastings. May I respond to that? No offense, but, you know, in our organization, when I hear an answer like that, I say to the organization, figure it out. Mr. Pallone. It is one thing to be able to do what they are doing now. But to go into totally new areas with cuts in funding, I don't see how. But whatever--let me go to Dr. Sigal, because I only have 40 seconds left here. I found the results of your study very interesting, the one comparing cancer approvals in the U.S. versus Europe, and I was surprised, given the claims about FDA's role in the innovation downturn, to see a document like that. What prompted you to do that study and what did you expect to find? Were you surprised by what you found? Ms. Sigal. I was very surprised. What prompted me was that we were hearing consistently from academic institutions, from developers, from biotech, from patients that the FDA is slower and things were getting approved faster in Europe, and we know the standards were very high in Europe. So we were very concerned and we did the initial research in house, we did it solely in house. And we were very shocked. As a matter of fact, we were so surprised that we had to validate it. I did not expect it. And I want you to know if in fact what we were told as urban legend were true and in fact we were slower, we would have published. So this was not a matter of getting data that we suspected was going to--we thought we were going to get data that showed that Europe was more innovative and faster, so we were very surprised at it and clearly it was very important. But there is still a lot more that needs to be done, because the science is complex and the agency is significantly underfunded for the innovation that they need to go forward. Mr. Pallone. Thank you, Doctor. Thank you, Mr. Chairman. Mr. Pitts. The chair thanks the gentleman and recognizes Dr. Burgess for 5 minutes for questions. Mr. Burgess. I thank the chairman. Just as a follow-up to Ranking Member Pallone's observations, last year twice Dr. Sharfstein came before this subcommittee, once with the DeCoster egg farm hearing and once with a hearing about are there problems with the pipeline and restrictions in the pipeline of getting drugs and products from NIH to the consuming public and is the FDA part of that obstruction. And both times Dr. Sharfstein testified in response to a direct question by me, do you need more money, and he assured me that the FDA had all the money that it needed. I knew that that must be right, because for those of you who sit up nights reading the Federal Register, you may know that we passed, Congress passed, I voted against it, but there was a big health care law about a year and a half ago, and it included no new money for the Food and Drug Administration in that big new health care law. Mr. Hastings and Mr. Leff, let me just ask you a question. If an innovator comes to the FDA and they have got something, a drug or device, characterize it as a black box, if you will, it does something good for patients, if that innovator comes to the FDA and asks for the pathway, what are my steps to go through getting this drug or device approved? Are they going to get clear direction and clear instruction from the FDA as to what procedures to follow? Mr. Hastings. We will get guidance, some guidance or recommendations on what to do in a situation like that. Mr. Burgess. If it is truly innovative, maybe something that hasn't happened before, are they likely to get an answer, ``we are not sure and you need to start and then we will provide you guidance as go along.'' Mr. Hastings. Well, it is very difficult in the case of a brand new innovation when there are no benchmarks to sometimes give guidance, because everybody is looking at the same thing and wondering what to do. I think that would therefore argue for the ability to communicate scientist-to-scientist and work together. This is also where some of these external advisers could come in and be very helpful experts in the field in terms of creating not a validated instrument that may take years to do this, but to create a risk-reward model to move that drug forward since it is the first in its class. That would be the ideal thing to do. Mr. Burgess. Forgive me for interrupting, but time is very limited. On this risk-reward model that you just articulated, does that exist within the FDA? If an innovator comes to the FDA and says I have got this, help me know the stems I must take to develop this and have it approved by the FDA, is that model in fact in place? Does it work? Mr. Hastings. I mean, I can't speak for the FDA. I think that model would probably work differently division by division, depending on who the reviewer is, depending on who runs the division. Mr. Burgess. That is the regulatory uncertainty. Again, I have people come to my office all the time with these complaints that I don't get clear direction about what I am going to need to provide and then it all changes in the course of development, and that obviously extends the timeline significantly. Mr. Hastings. Well, you made a very good point about changing it. And, again, I don't think this is anybody's particular fault, but I know of CEOs who are running diabetes companies where endpoints were changed in the middle of their Phase III clinical trials as they were ongoing and had to redo their Phase III clinical trial. Some of those companies shut down. Mr. Burgess. Sure. I wish we had more time to explore that, but Mr. Coukell, I need to ask you, you talked about the Heparin issue which we have studied in this committee, and I just wanted to reassure you that we do have an active and open investigation now. Last Congress it was a little bit difficult to get information from the FDA. Margaret Hamburg went to China and presumably talked to some of these individuals who were involved with the companies that produced the product that was contaminated with the adulterant. And you are correct, the adulterant was a very clever molecule that could hide behind the normal active pharmaceutical ingredient in Heparin on the normal testing with the mass spec. It almost had to be a criminal mind that decided to do this. I don't think it was accidental. But we have had significant difficulty in getting the data from the FDA as to where they are in this investigation, why the labs were confused and issues that you mentioned. I wanted to reassure you that the legislative remedy really is hard to come up with if you don't have the results of your investigation. Unfortunately, this investigation has taken a lot longer than I would have ever thought possible, but at the same time you run the risk of legislating with incomplete information. Mr. Coukell. Yes, sir. I commend your ongoing interest in drug safety. I think it is very important. I think it would be highly desirable to find the culprit in that case. Nevertheless, I think Heparin illustrates, as I outlined in my testimony, a lot of weaknesses that we know about now, and it was a wake-up call for a lot of folks in the industry and for the FDA. They have all said that. The next time it happens, it probably won't be Heparin. It will be somewhere else. I think we do know based on that case and others some of the things that we need to do now. Mr. Pitts. The chair thanks the gentleman and recognizes the ranking member emeritus, Mr. Dingell, for 5 minutes for questioning. Mr. Dingell. Mr. Chairman, I thank you for your courtesy and for the recognition. I will direct my questioning to Mr. Coukell. I would observe that I have great concern for the tremendous amount of pharmaceutical medicines and ingredients that are coming in from abroad. So I would like to address this with yes or no answers here. An increasing number of drug manufacturers are turning to outsourcing for pharmaceutical ingredients and manufacturers. As you mentioned in your testimony, up to 80 percent of pharmaceutical ingredients and up to half of the finished pharmaceuticals are purchased from clients in India and China. FDA is currently required to inspect U.S. drug facilities every 2 years, but there is no required frequency for inspection of foreign facilities. Food and Drug says that they investigate foreign facilities about once every 9 years. Is that sufficient or not? Mr. Coukell. It is not sufficient. Mr. Dingell. Now, until 2009 FDA did not have a dedicated staff for foreign inspections. Rather, employees qualified to do inspections would travel abroad. FDA now has a cadre of 15 inspectors dedicated to foreign facility inspections. Has this current cadre been sufficient to increase inspection of foreign facilities to a sufficient level that we can be comfortable that our supply of these pharmaceuticals is safe? Mr. Coukell. They improved the local FDA's local knowledge and have done some additional inspections, but they are not enough. Mr. Dingell. Thank you. Now, beyond inspections, quality manufacturing is also critical to a safe drug supply. In 2009, FDA issued 34 warning letters regarding adherence to good manufacturing practices, nearly double what was issued in 2008, ensuring manufacturing quality gets more difficult as supply chains move overseas and are more outsourced. Are today's GMPs sufficient to ensure manufacturing quality, yes or no? Mr. Coukell. No, sir. Mr. Dingell. As you have spoken to a number of stakeholders and experts about FDA's oversight of foreign drug manufacturing, what if any consensus exists for increasing foreign oversight and resources to support? Mr. Coukell. I can't answer that with one word, sir, but what I can tell you is we have been interested as we talked to stakeholders across the system, I have expected to have people say inspections aren't the answer. We didn't hear that. Inspections are part of an overall quality system. Some major sectors of the industry, including the generic manufacturers and the active ingredient makers, are on record as supporting fees to help fund additional inspections overseas, both for safety and to provide a level playing field for American manufacturers. Mr. Dingell. Thank you. One approach to ensuring manufacturing quality would be to require manufacturers to implement quality systems that detail management responsibilities, risk management practices, supply chain management, record keeping amongst other components. Do you believe requiring manufacturers to have in place a quality system would improve the safety of our drug supply chain? Yes or no. Mr. Coukell. Yes, sir. Those are recommendations now, but we need everyone to do it. Mr. Dingell. Should such a requirement relate not only to finished manufactured pharmaceuticals, but also to components and raw materials? Mr. Coukell. Yes. Mr. Dingell. Transparency throughout the supply chain is of particular concern and a valid one given the Heparin incident, but Heparin is only one of the examples of our problems. Currently, FDA recommends but does not require that companies conduct an on-site audit of a supplier. Do you believe requiring companies to perform on-site audits of suppliers before a purchase agreement is made would improve supply chain safety? Yes or no. Mr. Coukell. Our meeting heard that every supplier and sub- supplier should be audited by somebody. Mr. Dingell. Now, how frequent should these audits be to assure their effectiveness? Mr. Coukell. I think that depends on the material and the level of risk. Mr. Dingell. Could you give us some kind of a horseback guess? Mr. Coukell. I think it is going to depend, sir. If is a long-established relationship and a simple synthesis, it would be quite different from a new relationship with somebody who is making a very complex molecule. Mr. Dingell. Now, FDA recommends but does not require quality agreements with suppliers. Do you believe requiring quality agreements with suppliers would improve supply chain safety? Yes or no. Mr. Coukell. Yes, sir, and I believe leading companies are already doing that. Mr. Dingell. Mr. Chairman, I apologize. I have a couple more. May I pursue my business to its end? Mr. Pitts. You may proceed. Mr. Dingell. Thank you. You are most courteous. More must also than done to ensure transparency and access to information for products being imported into the United States. Do you believe requiring importers and customs brokers to register with the FDA would help to improve FDA's general oversight of global drug production as well as drug safety assessments at the border? Yes or no. Mr. Coukell. Yes. Mr. Dingell. It is clear then that increasing foreign inspections and improving transparency and quality throughout the supply chain are necessary components to increasing the safety of our drug supply, and that would also include raw materials and components as well as finished products. I would also add, Mr. Chairman, that H.R. 1483 would address the vulnerabilities that we have just outlined. I thank you for your courtesy, and I thank our panel for their assistance to the committee. Mr. Pitts. The chair thanks the gentleman. Without objection, the chair recognizes Mr. Bilbray from California for 5 minutes for questions. Mr. Bilbray. Thank you very much, Mr. Chairman. Thank you for a chance to ask questions. I want to thank the ranking member for being here, because I think that this is an issue that we can have a bipartisan effort on. From personal experience in working with the ranking member for probably a decade, about a decade-and-a-half I think it has been, we have had a bipartisan effort going on water quality issues. I think this is one of those things that the ranking member can join with the majority in actually addressing an issue that knows no party affiliation. Mr. Hastings, one of the crises that I am seeing in my district with my bio-med research people is the fact that we have lost 50 percent of the venture capital for what we used to say in environmental issues would be the economic soup, the startup companies, the little guy who is the krill of the bio- system; in other words, where the ideas and the innovation comes from that the big guys eat up, adopt and then develop into it. We have lost 50 percent of that capital. It looks like we could lose 50 percent of that overseas if we don't do something. One of the items that has been brought up to me is how do we infuse and get venture capital back into the field, and one of the items is the issue that we have over $2 trillion of American capital overseas. Do you think that it would help in trying to backfill that loss of 50 percent if the Federal Government looks at changing the repatriation laws here to hold harmless if they bring the money back for research and development? Mr. Hastings. Resoundingly absolutely. Mr. Bilbray. Anybody else got a comment on that or concern with that? Mr. Leff. Yes, I agree it would absolutely help and it would bring capital back into this country and release additional investment and innovation. The observation I would make, though, is that would be a one-time benefit to the system. It wouldn't change the trajectory necessarily that we are on and the fundamental underlying reasons that capital is leaving investment and innovative life sciences companies. Mr. Bilbray. I appreciate that. I was a public safety guy. I am just a lifeguard that triaged people and got more votes than the next guy. But we do have a patient that is hemorrhaging, needs an infusion, an infusion to survive, and I think this is one thing we may be able to ask both sides to work on. Let me ask, Doctor, speaking of looking at systems, back in the nineties there was a bipartisan effort made that did things on the AIDS epidemic that we had not done for anybody else, extraordinary efforts. We broke the rules, changed the rules, forced the bureaucracy to respond, and I think history has proven that was a great success. Sadly, it looks like we did this great success and walked away from it. In those days we had Act Up, we had Men's Gay Health Crisis Project, we had the Treatment Action Group putting pressure on us to change the system, and we actually allowed patients to be at the table. We allowed, and the doctor can go over it, whole different protocols for what was allowed to be counted as a positive action, and we basically broke the mold and tried innovative issues. Is there any reason in the world why we should not go back and look at what was successful in addressing the AIDS crisis and apply it to the crisis we are finding right now? A good example is why would we allow an AIDS patient on a review body for AIDS, but would not allow a cancer patient to have the same right to be able to participate? Doctor, I solicit your comment about how we can address that. Ms. Sigal. Thank you for the opportunity. I think the HIV model is a wonderful model. It started activism, and, most importantly, it has had an impact. It helped patients, it helped science, and it made a huge difference. It is a complex scenario though, because there we had a fire marker. We had the CD 4. We had viral load. We knew what we were looking for. But it did start advocacy, and I would agree with you fully that patients have not only a role but a right to sit at the table. Ultimately these decisions impact them. They need knowledge, they need the ability to have the information, and they have the ability and should have the ability to be at the table when these decisions are made. We, along with the National Health Council and others, are working on that and believe that we have opportunities in the reauthorization of the User Fee Act to have a more active patient voice. It is essential that they be at the table, because we do impact them. Mr. Bilbray. The one thing I saw work in the AIDS community was the degree of urgency was brought on to the bureaucracy, the sensitivity that they know had an impact, an adverse impact just by denying, that at least there was opportunity there. What I am concerned about is the study that you did showed that if you take the long-range, there was an item. But my question is, recently though it looks like the European Community's review and our review are starting to close that gap since 2008. Do you have any way of explaining why though the trajectory looked real good on cancer drugs over the long term, recently it looks like we are converging or going to be crossing? In that study, did you identify why since 2008 it looks like the numbers are changing? Ms. Sigal. Actually we did go past, we did look at that. And in fact, since we have concluded our study, we have had three more approvals which they still do not have in EMA. So in fact the trend of earlier approval, faster approval, is continuing. The problem is the complexity of the science. The science is very, very, very hard. But this is not an issue of speed, this is an issue of quality, and I can tell you as an advocate myself we in the cancer community and other advocates of deadly diseases, childhood cancers, other cancers, are just as anxious as anyone to have these new drugs approved, because it will---- Mr. Bilbray. Let me tell you as a father, I am in that category. Mr. Chairman, I appreciate the time. I think one of the things both sides need to talk about is the conflict of interest regulations that historically have been with FDA and these review bodies, because now you are getting, especially in cancer, you are getting items coming forward that the discipline is so limited of anybody who can make an informed decision that you have to bring somebody in from outside and somebody who has a connection to basically development and certain research to be able to get the expertise to make an informed decision. I don't think any of these conflict of interest requirements that we put in in the past was meant to exclude people that were essential to making informed decisions. I hope both sides can look at modifying those rules. Mr. Pitts. The chair thanks the gentleman. That concludes the first round of questioning. We will go to one follow-up on each side, if we have any. Dr. Burgess. Mr. Burgess. Thank you, Mr. Chairman. I appreciate the recognition. Mr. Boutin, if I could along that line of the advisory panels and the conflict of interest exclusions, are the restrictions on who can serve on advisory panels hindering activities to bring new drugs to market? Mr. Boutin. Yes. I think there is a real challenge. Right now, the FDA is charged with looking at multiple regulatory and legal requirements for conflict of interest, and the standards within each are not necessarily inconsistent, they are different. As a result, the FDA has had to look at how do we apply them all together. In the previous reauthorization of the prescription drug user fee, there was an additional requirement that compelled FDA to limit its use of waivers, and as a result they took a look at how they would apply the conflict of interest rules. In their new look, they acknowledge that they are being more strident in addressing the conflicts, and as a result what you are seeing is it harder to fill the advisory committees, and currently about 25 percent of the advisory committees are vacant, and as a result there is delays in having the advisory committees meet and the FDA has acknowledged that it has led to delays in the approval of new treatments. So from our perspective, we need to look at this carefully. Conflict of interest rules are important and we recognize they provide credibility and transparency to the process, and nobody is suggesting they should just be done away with. However, we have to balance the need for transparency and managing of conflict of interest with the need to ensure that we get treatments to people who need them. Mr. Burgess. That was a subject of a lot of discussion when we marked up this bill in 2007 and recognizing that for some products. Pediatric antineoplastic plasma medications, the universe of people that understands these is probably very small, and it is probably very difficult to find someone who has not worked in some way on the development of that product at some point along the line. This was really where we painted ourselves into a corner. Mr. Chairman, I hope we will be serious about fixing this. And your thoughts on things that we might do to relax or keep the appropriate focus where it needs to be but at the same time allow these advisory panels the ability to form and do their work, I think that is going to be critically important when we reauthorize. Thank you. Mr. Pitts. The chair thanks the gentleman. I don't see any other questions. That concludes today's hearing. I remind members they have 10 business days to submit questions for the record. I ask that the witnesses all agree to respond promptly to these questions. With thanks to the witnesses, this subcommittee is adjourned. [Whereupon, at 1:20 p.m., the subcommittee was adjourned.] [Material submitted for inclusion in the record follows:] [GRAPHIC] [TIFF OMITTED] T2917.085 [GRAPHIC] [TIFF OMITTED] T2917.086 [GRAPHIC] [TIFF OMITTED] T2917.087 [GRAPHIC] [TIFF OMITTED] T2917.088 [GRAPHIC] [TIFF OMITTED] T2917.089 [GRAPHIC] [TIFF OMITTED] T2917.090 [GRAPHIC] [TIFF OMITTED] T2917.091 [GRAPHIC] [TIFF OMITTED] T2917.092 [GRAPHIC] [TIFF OMITTED] T2917.093 [GRAPHIC] [TIFF OMITTED] T2917.094 [GRAPHIC] [TIFF OMITTED] T2917.095 [GRAPHIC] [TIFF OMITTED] T2917.096 [GRAPHIC] [TIFF OMITTED] T2917.097 [GRAPHIC] [TIFF OMITTED] T2917.098 [GRAPHIC] [TIFF OMITTED] T2917.099 [GRAPHIC] [TIFF OMITTED] T2917.100