TESTIMONY BY MYRON GENEL, MD, FAAP FOR THE BEFORE THE SENATE HEALTH, EDUCATION, LABOR AND PENSIONS COMMITTEE IMPLEMENTATION OF THE FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT OF 1997 OCTOBER 21, 1999 Endorsed by: Ambulatory Pediatric
Association Good morning. I am Myron Genel, MD, a pediatrician and professor of pediatrics at Yale University School of Medicine where I direct the medical school’s Office of Government and Community Affairs. Formerly, I served for 16 years as Program Director of Yale’s Children’s Clinical Research Center and as Chief of the Section of Pediatric Endocrinology. I am pleased to be here this morning representing the American Academy of Pediatrics and its 55,000 pediatricians and pediatric subspecialists who have committed themselves to helping improve the health of children. In addition, I am representing the Pediatric Academic Societies, comprised of the American Pediatric Society, the Ambulatory Pediatric Association, the Association of Medical School Pediatric Department Chairs, and the Society for Pediatric Research. These organizations consist of pediatric researchers, full time academic and clinical faculty responsible for the training of pediatricians, and the leadership of medical school pediatric departments. I begin with warm praise and gratitude for the important work that the Congress undertook when they passed the pediatric studies provision within the Food and Drug Administration Modernization Act of 1997 (FDAMA) (P.L. 105-115). Your efforts to increase the number of pediatric studies conducted with drugs used in infants, children, and adolescents has resulted in a rapid increase in the number of studies which pharmaceutical companies are undertaking. In the 16 months since the issuance of guidance to the industry for the pediatric studies provision of FDAMA there have been over 220 requests made by the Food and Drug Administration (FDA) for studies on important drugs that need additional pediatric information. Previous attempts by FDA to secure more pediatric use information resulted in only 65 submissions of adequate pediatric information over a 2 ½ year period. The increase in the number of drugs studied for children is unprecedented. This increase begins to address the deficit in the study of drugs in children that developed during the 37 years following the Kefauver-Harris Amendment of 1962. That amendment to the Food Drug and Cosmetic Act began the requirement that drugs be studied and labeled for the disorder they are intended to treat, and children were left out of most of those studies until the passage of FDAMA. Rarely is it possible to witness such dramatic advances in such a short period of time. This story could not be possible without the leadership of the Congress, the guidance of the FDA, the interest of the pharmaceutical industry, and yes, the prodding of pediatricians like myself. We have been caring for children throughout our professional careers without sufficient information about the therapeutic medicines with which we must treat our young patients. Congress and the FDA have heard our pleas and have acted in a responsible and reasonable way. The FDA deserves the thanks of health professionals, parents and pediatric patients for the many long hours and the perseverance with which they have developed guidance and implemented the pediatric studies provisions of FDAMA. Many of the staff at the FDA have been working 60 hour weeks to see that the pediatric studies provisions have the best chance possible to meet the needs of children. They deserve recognition and help through additional personnel to maintain this progress. THE STARS ARE ALIGNING FOR CHILDREN’S THERAPEUTICS It may have taken longer than we had hoped, but the stars are beginning to align for children’s therapeutics. The AAP and the Pediatric Academic Societies have been enthusiastic supporters and a staunch defenders of the independent and complementary efforts both Congress and FDA took on behalf of the pediatric population. And we watch and wait for evidence that the ultimate goal of this legislation is being reached – that the number of new and already marketed drugs are not only studied in infants, children and adolescents, but are also labeled for treatment of pediatric patients to provide lasting guidance for all physicians who prescribe medications for young patients. In 1997, Congress lead the way by establishing a five-year demonstration program intended to improve the information available to health professionals who care for infants, children and adolescents. The six-month extension of the market exclusivity of new and already marketed drugs for which pediatric studies are completed has proven to be a very effective incentive that pharmaceutical companies are pleased to embrace. The hope is that incentives provided by the FDAMA legislation will yield sufficient information to lead to pediatric drug labeling; but the reality is that incentives alone will not complete this critical process for children. Not all drugs for which pediatric information is needed will be captured by the FDAMA legislation. There is a need for other mechanisms to move toward getting adequate drugs studied and labeled for pediatric use. So in 1998, the FDA released regulations that would complement the new pediatric studies law. Recognizing that there would be gaps in the type and scope of drugs captured by the law, FDA put in place regulations that would require pharmaceutical companies to study new and already-marketed drugs for pediatric populations in certain circumstances. One of the most significant components of the regulations is the requirement that new drugs and biological products contain adequate pediatric labeling for the approved indications at the time of, or soon after, approval of the drug. The importance of this component of the regulation can not be overstated. These regulations would catch drugs whose patents will expire too soon to take advantage of the incentive. Another example is that a drug may not be deemed as necessary for pediatric study by the pharmaceutical industry, though pediatricians and other health professionals may view it as an important drug for children. It is in these, and other circumstances, that the FDA has the ability to requires that studies be conducted for pediatric populations. It should be noted that FDA believes that with FDAMA provisions in place it may diminish the need to exercise the agency’s authority to require studies. Even with the important advances we have just highlighted, there remains an outstanding therapeutic issue for children. Off-patent drugs need to be labeled for pediatric populations. This is a large and very important group of drugs with limited pediatric labeling. Neither FDAMA’s pediatric exclusivity provision nor the 1998 FDA regulations capture drugs whose market exclusivity has expired (the so-called "off-patent" drugs.) Currently, there is little incentive for companies to conduct pediatric studies. AAP would like to explore avenues for getting these off-patent drugs studied in pediatric populations. HIGHLIGHTS OF FDA PEDIATRIC DRUG STUDY EFFORTS: The last two years have been a whirlwind of activity for pediatric therapeutics at FDA. Remarkable progress has been made, thanks to the long hours logged by FDA staff. With limited staff resources, the FDA has managed to adhere to congressionally mandated timelines, finalize regulations and even field some unexpected challenges related to the implementation of FDAMA. The AAP and Pediatric Academic Societies are pleased to have been an active part of the discussions and to provide formal comments throughout the implementation of the pediatric studies provision of FDAMA and in the final regulations. Several key provisions should be highlighted: "The List": A component of the FDAMA law is the issuance by FDA of a list of drugs for which additional pediatric information is necessary (commonly referred to as "The List"). The List is to be updated at least annually. In May 1998, the FDA issued the first list, which included 500 drugs. The AAP strongly advocated for a comprehensive list of drugs, noting that the number of FDA-approved drugs used in the pediatric population numbers in the thousands. To suggest that a few hundred drugs need to be studied in the pediatric population is a reasonable and appropriate use of resources. An updated List was issued in May 1999. Guidance for the Industry: Qualifying for Pediatric Exclusivity Under FDAMA: The FDA issued guidance that the AAP believes outlines necessary and appropriate parameters for submissions of certain pediatric studies by the industry while maintaining the flexibility to design pediatric studies on a case-by-case basis. The FDA requirement that reports of pediatric studies be submitted in accordance with requirements for filing of a supplement or new drug application is a critical component in moving toward the goal of getting more drugs labeled for pediatric populations. Pediatric Advisory Subcommittee: As part of the 1998 regulations, FDA called for convening a panel of pediatric experts to seek advice on a range of issues related to the implementation of the regulations. AAP had long advocated for this kind of formal dialog between FDA and members of the pediatric community. The first meeting was held in April 1999. Generic Drug Industry Opposition: The FDA faced a court challenge from members of the generic drug industry to halt the implementation of the FDAMA pediatric studies provision. Opposition centered on accusations that FDA did not honor statutory requirements related to the development of "The List" and that the public interest would be served by granting an injunction to immediately halt the implementation of the pediatric provision within FDAMA. The case was filed in U.S. District Court for the District of Columbia on February 19, 1999 and led to an April 9, 1999 hearing by Judge James Robertson. In a April 20 decision, Judge Robertson denied the preliminary injunction and on May 14, 1999 the Generic Drug Industry withdrew from the case and it was dismissed. CHALLENGES AHEAD Evaluation is a critical component of the pediatric studies provision within FDAMA. Congress will rightfully judge this important demonstration project to assess its effectiveness. As pediatricians, we will also be assessing it to determine whether the studies that have been undertaken ultimately yield the kinds of label changes and additional information that will provide information that makes prescription drug therapy for children safer. The AAP and Pediatric Academic Societies have strongly urged FDA to develop a tracking system of drugs on "The List". A key element of such a system is identifying the scope, nature and type of labeling changes for various pediatric populations that were accomplished as a result of FDAMA. Information collected would be of great interest and use to pediatricians and other health professionals who prescribe medication to pediatric populations. This information would also be essential in preparing FDA’s January 1, 2001 report to Congress on the effectiveness of the pediatric studies section of FDAMA. Congress must evaluate the importance and effectiveness of the information generated by the exclusivity program about important pediatric uses for approved drugs, as well as the adequacy of the incentive provided under this section. We are eager to assist FDA in designing an appropriate tracking system. New challenges arise related to the rapid increase in the number of pediatric studies underway as the implementation of FDAMA continues. While the AAP and Pediatric Academic Societies are very pleased with the enthusiastic response by the pharmaceutical industry to the written requests being made the by FDA for pediatric studies, a note of caution must be sounded. It is incumbent upon all parties to maintain the highest research standards for children who participate in study protocols related to this provision. Even while moving expeditiously to address an important need for additional pediatric drug information, we must be ever mindful and extremely diligent that protections for children are adhered to in the spirit and letter of the law. Children comprise an especially vulnerable population and must be provided added protection against violation of their individual rights and exposure to unnecessary risk. Unlike adult volunteers, children involved in most studies are receiving drug treatment for their underlying disorders. In this situation, some risk will accompany their participation along with benefits of improved treatment. The federal government has developed guidelines and regulations that provide important standards for the involvement of infants, children and adolescents in pediatric trials. These guidelines serve to establish acceptable and workable approaches to protect children and serve as the foundation from which academic and private Institutional Review Boards (IRBs) base their reviews of clinical trials. The number of pediatricians who are being asked by the pharmaceutical industry to participate in clinical trials is growing almost as rapidly as the number of studies. The AAP is developing workshops to educate pediatricians about the responsibility and the appropriate role they play in research protocols that involve pediatric patients. AAP policies such as Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations are an important tool in training and educating pediatricians and other health professionals. CONCLUSION The AAP and Pediatric Academic Societies are pleased with the progress FDA has demonstrated in the first two years of the implementation of the pediatric studies provision of FDAMA. Much progress has been made -- much progress remains. In summary, the AAP and Pediatric Academic Societies would recommend the following:
The American Academy of Pediatrics and the Pediatric Academic Societies offers our expertise to the Congress and the Food and Drug Administration as we all partner together to develop more and better ways to care for the health needs of infants, children and adolescents. Thank you for the opportunity to be here today. I would be happy to take any questions you may have. |