Docket Management
Docket: 02N-0152 - Timely Pediatric Studies and Adequate Pediatric Labeling for Human Drugs and Biologics
Comment Number: EC -77

Accepted - Volume 3

Comment Record
Commentor Dr. Charles J. Coté Date/Time 2002-07-08 16:35:28
Organization Children's Memorial Hospital
Category Individual

Comments for FDA General
Questions
5. General Comments Charles J. Coté, M.D. Vice Chairman Director of Research 773/880-4414 (Phone) 773/880-3331 (fax) ccote@northwestern.edu July 8, 2002 Dockets Management Branch (HFA-305) Food and Drug Administration 5630 Fishers Lane – Room 1061 Rockville, MD 20652 http://www.fda.gov/dockets/ecomments Docket Number: 02N-0152 Dear Sir or Madam: As a pediatrician and anesthesiologist who cares for infants and children every day, and as a former member of the Committee on Drugs of the American Academy of Pediatrics, I welcome the opportunity to comment on the relationship between the 1998 Pediatric Rule and the Best Pharmaceuticals for Children Act (P.L. 107-109). The AAP has long pressed for the development of appropriately tested and labeled medications for infants, children and adolescents. There has been great progress but the job is not yet complete. A dual approach to obtaining essential pediatric data was instituted in the late 1990’s. This approach combines: 1) incentives for voluntary studies of drug safety and dosing by industry (extended in January 2002 in the Best Pharmaceuticals for Children Act [BPCA]); and 2) a regulation requiring pediatric studies of new drugs and some already marketed drugs, known as the Pediatric Rule. In March 2002 the FDA proposed to suspend the Pediatric Rule. While this proposal was reversed, this action indicates that children are at risk of losing the ground we have fought so hard to secure for them. Having published a number of papers regarding sedation accidents in children and having served as an expert witness in a number of medical malpractice cases, it is clear that we must continue the battle to assure drug safety in children. In particular the proper labeling of new drugs must go hand in hand with the proper labeling of the old drugs that are no longer patent protected. The Pediatric Rule ensures that children are no longer a therapeutic afterthought by the pharmaceutical industry. It is an essential and successful tool in ensuring that children have the quality and quantity of drugs they need. All new drugs must be studied for pediatric use at the time a drug comes to market unless the FDA grants a waiver. This makes medications for children a certainty, not an option and puts children on a level playing field with adults for the first time. I believe that all components of the 1998 Pediatric Rule must be preserved especially those components that fund research in off patent medications. It is a comprehensive approach to securing pediatric studies. FDA has not yet invoked all the provisions of the Pediatric Rule; however, together they weave a safety net for children. It is my belief that many medication related accidents could have been avoided had there been better labeling in the package insert. Pediatric formulations must be developed for all pediatric patients, particularly our very vulnerable neonates and toddlers. How can we expect infants to ingest pills when a liquid is the only option yet no liquid formulation with approved bioavailability bioequivalency is available? The following comments and recommendations respond to questions and issues raised in the Federal Register notice soliciting public comments: · Retiring or relaxing any authorities currently in the Pediatric Rule is inappropriate and would be to the detriment of children. It must always be kept in mind that BPCA is time-limited, voluntary and subject to continuation by the Congress. Those facts speak directly to the need to ensure that the Pediatric Rule remains in place in its entirety. · Noting again that the BPCA is subject to continuation by Congress and that future reauthorization is uncertain, the Pediatric Rule should mirror the scope of the BPCA and apply to all labeled and potential indications as well as new indications. If a company submits a supplemental indication to the FDA, it invokes the Pediatric Rule. It is important that appropriate pediatric studies be conducted for that new use; and if the current label lacks appropriate pediatric use information (e.g., for neonates) the FDA should also include in their requirement for pediatric studies of the new indication, any pediatric studies that may be needed for the currently labeled or potential indications. · In determining the process of when pediatric studies are conducted, the FDA should rely on the detailed process for requesting pediatric studies of already marketed drugs and securing labeling that is outlined in the BPCA. · It is essential that the Pediatric Rule remain in place because it is the only mechanism that ensures that biological products will be studied and available for children. No provision of BPCA applies specifically to biological products since the legislation focuses on drugs covered by the Food, Drug and Cosmetic Act (FDCA) and the vast majority of biologics are covered under the Public Health Service Act. Moreover, some of the most innovative new therapies now and in the future are biological products, which are not covered under BPCA. · Appropriate formulations are an essential component of providing medications for the pediatric population. It is a requisite for studies in infants and younger children to develop age appropriate formulations, if necessary. Failure to require needed formulations for specific age populations negates the intent of the BPCA and the Pediatric Rule. · BPCA limits its reference to “recommendation” for formulation changes only to studies completed under public contract. This provision was included to acknowledge that once a formulation is developed in the study phase, while it may be necessary to manufacture that formulation, it may not always be possible to scale up the formulation for distribution to the general public. Thank you for your consideration of these comments. I would be honored to deliver testimony in person at any time. Sincerely, Charles J. Coté, M.D. Vice Chairman Director of Research Department of Pediatric Anesthesiology Children’s Memorial Hospital Professor of Anesthesiology and Pediatrics Northwestern University Medical School




EC -77