Janet Woodcock, M.D.
Director, Center for Drug Evaluation and Research
Food and Drug Administration
U.S. Department of Health and Human Services (HHS)
FDA's Budget for Evaluating the Safety and Effectiveness of Drugs
Committee on Appropriations
Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies
U.S. House of Representatives
Wednesday February 27, 2008
Chairwoman DeLauro, Congressman Kingston, and members of the Subcommittee, I am Janet Woodcock, M.D., Deputy Commissioner of the Food and Drug Administration (FDA). I am here to discuss the mission of FDA’s Center for Drug Evaluation and Research (CDER) and FDA’s budget for evaluating the safety and effectiveness of drugs. Joining me for today’s hearings is David Horowitz, Deputy Associate Commissioner for Compliance Policy in FDA’s Office of Regulatory Affairs (ORA).
Funding for the FDA Human Drugs Program
The FY 2008 appropriation contains important increases of $21 million for drug safety (including $10 million for the Office of Surveillance and Epidemiology, or OSE), $7.5 million for the Critical Path program, $6 million for generic drug review, $4 million for the review of direct-to-consumer advertising, and increased funding to meet Drug Program payroll obligations. As you know, these amounts are all subject to the FY 2008 across-the-board rescission. Thank you for your strong support for FDA efforts to achieve its public health mission related to drug safety and development.
The President’s budget proposes an FY 2009 total program level of $739 million for the Human Drugs Program. This includes a $5 million increase in budget authority and an increase of $54 million in fees under the Prescription Drug User Fees Act (PDUFA) and the proposed Generic Drug User Fee Program. The PDUFA fee increase supports FDA’s ability to achieve the drug review, drug safety, drug development, and related priorities authorized by Congress in the Food and Drug Administration Amendments Act of 2007. The PDUFA fee increase also allows FDA to improve information technology to support human drug review. The new Generic Drug User Fee Program will allow FDA to improve generic drug review performance and allow Americans to enjoy greater benefits from generic alternatives. The FY 2009 increase in budget authority funds the annual pay increase for Human Drugs Program employees and allows ORA field operations to improve the safety of imported drugs by increasing import investigations related to counterfeit drugs and other areas of criminal drug activity.
The Value of Drug Regulation
Prescription and over-the-counter drugs are an increasingly critical component in improving the health of Americans. New drugs – and new uses for older drugs – save lives, reduce suffering, and improve the quality of life for millions of Americans. While drugs account for an ever-increasing fraction of the rapidly rising cost of healthcare, innovative new medicines play a significant role in increasing life expectancy in the United States and around the world. Medicines also prevent or slow the progress of many diseases and avoid costly invasive treatments, hospitalizations, and nursing home stays. However, the more widespread use of medications also has had negative consequences. Harm from inherent side effects, misuse, overuse, medication mix-ups, and intentional abuse of drugs has increased. These problems must be vigorously monitored and mitigated.
Thus, FDA responsibilities for oversight of the entire life-cycle of drugs – from pre-market drug testing and development through drug approval, post-market surveillance, and risk management – have never been more important. FDA’s mission is to ensure that safe and effective new drugs are available as quickly as possible and that drugs already marketed remain safe and of the highest quality. We at FDA must continuously adapt to provide a pathway for translating new scientific advances into benefits for patients and to take advantage of new ways to monitor the performance of marketed drugs.
Ensuring the safety of drugs from their earliest introduction into humans during clinical trials and throughout the period when an FDA-approved drug is marketed is a cornerstone of FDA’s mission. CDER dedicates at least half of its pre-market review activities to evaluating the safety of investigational drugs and overseeing the safety of clinical trial participants. ORA supports the premarket drug review process by inspecting clinical trials. CDER is in the process of improving its ability to evaluate post-market drug safety and to implement risk management steps.
Drug safety relies on a foundation of drug quality. Improperly manufactured drugs and drugs that are contaminated or illegally marketed can cause significant harm to patients. For this reason, FDA devotes considerable effort to reviewing and monitoring drug manufacturing activities. FDA’s ORA field operations conduct risk-based domestic and foreign inspections of drug manufacturers, and ORA monitors drug imports.
FDA increasingly faces challenges due to globalization of drug development and manufacturing. Not long ago, most drugs were developed, studied, and manufactured in the United States. Today we routinely review and monitor drugs – both innovator and generic – that are studied or manufactured, at least in part, outside the United States. The supply chain for finished drugs and active drug ingredients now frequently links to manufacturing sites in countries such as China and India. With the globalization of the supply chain, FDA faces an ever-growing number of brokers, traders, distributors, repackagers, and other players involved in the import of pharmaceuticals. The changing world – including the fundamental challenges of many different languages and protocols – requires FDA to devise and evaluate more complex risk scenarios and apply more sophisticated technologies to screen and evaluate drugs entering the United States to ensure their quality.
Our generic drug program illustrates the dramatic changes during the last 10-15 years. Since 1992, we witnessed a 400 percent increase in the number of foreign establishments named in generic drug marketing applications. Today, in India alone, there are nearly 25 times as many drug establishments as there were eight years ago (867 compared to 37). Growth in FDA’s capacity to inspect generic drug manufacturing facilities has not been commensurate with this global expansion. FDA’s FY 2009 budget proposal for Generic Drug User Fees will assist FDA to respond to some of these challenges. Yet FDA must be able to determine that facilities named in drug applications will meet FDA standards for marketed drug safety, effectiveness, and quality, no matter where they are located.
Another trend we face is the geographical dispersion of clinical trials. Traditionally, industry-sponsored clinical trials were conducted in North America and Western Europe. Today, however, clinical trials in foreign countries are much more common. Clinicaltrials.gov contains data on a recent set of 36,000 clinical trial descriptions where studies were conducted (in whole or in part) in more than 140 countries.
Recent Activities in Drug Safety
Increased attention to safety issues within FDA and growing concern from consumer advocates, health professionals, academic researchers, the media, and Congress prompted FDA to reassess its efforts to ensure that its drug safety program is the best possible.
During the past decade, CDER launched a number of important steps to modernize the drug regulatory system. These steps include:
- Drug Quality for the 21st Century, a quality systems approach to assure Current Good Manufacturing Practices (cGMPs) and other aspects of drug quality
- the Unapproved Drugs Initiative, to make sure that marketed prescription and over-the-counter drugs have been shown to be safe and effective
- the Generic Initiative for Value and Efficiency, to help FDA modernize and streamline the generic drug approval process.
Also during the past decade, perhaps the most notable shift in drug regulation resulted from PDUFA, which brought unprecedented accountability to the new drug review. PDUFA also institutionalized project management, prioritization, and tracking for drug review.
CDER is also transforming its post-market drug safety program. CDER is accomplishing this transformation with extensive input from our many stakeholders and with advice from many drug experts – including the 2006 study on drug safety by the Institute of Medicine (IOM) sponsored by this subcommittee. CDER is also drawing on lessons learned from previous regulatory modernization initiatives to transform drug safety.
In response to the 2006 IOM report, CDER entered into a contract with the Center for Professional Development to foster a truly collaborative, multidisciplinary, team-based approach to drug safety within the center. CDER is committed to improving workplace leadership, empowering staff, and establishing more effective business practices. The goal is to create a sustainable environment of open and transparent communication, collaborative decision-making, and improved morale and staff retention.
I want to highlight other recent FDA initiatives to improve drug safety through new science, product quality, and institutional change.
FDAAA Drug Safety Improvements: The Food and Drug Amendments Act (FDAAA), a sweeping new act of Congress signed by the President in September 2007, acknowledges FDA’s critical role in assuring the safe and appropriate use of drugs after they are marketed. FDAAA gives FDA substantial new resources for medical product safety and new regulatory tools and authorities to ensure the safe and appropriate use of drugs.
FDAAA directs FDA to shift its regulatory paradigm. With the goal of maintaining a systematic and scientific approach to evaluating benefit versus risk throughout the drug life-cycle, FDA must build the scientific and administrative capacity as an active and collaborative player in the delivery of safe and effective drugs to patients.
Strengthening Science: FDA is working to strengthen the science that supports drug safety at every stage of the drug life-cycle, from pre-market drug testing and development through post-market surveillance and risk management. With the evolution of science underpinning drug development, the focus on empiric data derived from randomized clinical trials has expanded to include, for example, biomarkers and pharmacogenomics, which help maximize the safe and effective use of drugs in individual patients. New scientific methods and tools are emerging to target a specific drug to specific patients where the benefits relative to risks are maximized. A primary objective is to prevent adverse events by predicting drug safety problems before they can cause injury. The goal is to combine new understandings of disease and its origins at the molecular level (including adverse events resulting from treatment) with emerging knowledge about the unique genetic and biologic features of an individual patient that determines how the patient will respond to treatment. If successful, these innovative, efficient, and risk-based drug development processes will improve FDA’s ability to detect safety-related problems earlier. In addition, FDA is currently exploring, testing, and developing new methods of signal detection, data mining, and analysis of patient-level electronic health care data. These new methods will complement our existing passive post-market surveillance system by generating hypotheses about and confirming the existence and cause of safety problems. FDA operates strong safeguards to ensure the security of safety data and to protect the privacy of patients.
International Quality: During the past decade, FDA has been keenly aware of the globalization trend. To respond proactively to this global challenge, FDA developed a variety of solutions. FDA requires facilities that manufacture drugs for the U.S. market to meet FDA’s current good manufacturing practice (cGMP) requirements. FDA conducted 498 foreign pre-approval, cGMP, and bioresearch monitoring inspections during FY 2007, an increase of 45 percent from the previous year. We will soon begin implementing an electronic system for accepting and processing drug establishment registration and listing. Electronic registration and listing will provide FDA with a more accurate and thorough accounting of drug manufacturing firms and locations. FDA entered into a number of cooperative relationships with foreign regulators, ranging from cooperation under a Free Trade Agreement, to agency-to-agency Memoranda of Understanding, to more informal arrangements to advance drug quality.
Improving Communications: FDA is continuing work to encourage greater transparency and to ensure that patients and healthcare providers have access to emerging new safety information and the most up-to-date and complete information necessary to inform their treatment decisions. In September, 2007, FDA released the first issue of a new Drug Safety newsletter. The newsletter, to be published online quarterly, provides information for healthcare professionals about the findings of selected post-marketing drug safety reviews, important emerging drug safety issues, and recently approved new drugs.
On November 5, 2007, FDA announced the selection of 15 voting members to serve on its Risk Communication Advisory Committee. The Committee will advise FDA about how best to communicate to the public about the risks and benefits of all FDA-regulated products to promote their optimal use. The first meeting of the Risk Communication Advisory Committee is scheduled for February 28, 2008.
Strengthening Drug Safety Operations and Management: CDER is taking steps to rebalance the Center’s efforts and resources devoted to drug development and post-market drug safety. The goal is to recalibrate the focus on pre-market review and post-market safety and align our policies and processes to ensure that the most appropriate and best-qualified experts lead or have a strong voice in regulatory decisions. CDER is establishing positions in each review division in the Office of New Drugs (OND) devoted to managing pre- and post-market drug safety issues, including a Deputy Director for Safety and a Safety Regulatory Project Manager. We are establishing new roles and responsibilities for staff in the OSE, including delegating authority to OSE for certain regulatory actions, such as review of proprietary names, medication errors, and observational epidemiologic studies. In addition, CDER is also taking steps to provide a focus, intensity of tracking, deadlines, and accountability for post-market safety activities that equals our focus and performance on pre-market safety, efficacy, and quality review.
FDA has a strong safety record and remains the world’s gold standard for drug approval and safety. No drug is absolutely safe. FDA approves drugs only after the drug sponsor demonstrates that a drug’s benefits outweigh its risks for a specific population and a specific use, and that the drug meets the statutory standard for safety and efficacy.
When we talk about drug safety, we are really talking about working to ensure a favorable benefit-to-risk balance and ensuring that health care providers and patients have access to up-to-date information about the benefits and risks of drugs so that they can make the best individual treatment decisions. Recent FDA initiatives to balance FDA pre-market review and post-market safety efforts and maintain a systematic and scientific approach to a drug’s benefit-to-risk balance throughout the drug life-cycle are evidence of our commitment to the health and safety of patients who use FDA-approved drugs.
Thank you for allowing me to testify. I am happy to respond to your questions.
Last revised: June 18, 2013