Docket Management
Docket: 02N-0152 - Timely Pediatric Studies and Adequate Pediatric Labeling for Human Drugs and Biologics
Comment Number: EC -61

Accepted - Volume 3

Comment Record
Commentor Dr. Paula Botstein Date/Time 2002-07-05 16:31:46
Organization Botstein Associates
Category Health Professional

Comments for FDA General
1. What changes to the pediatric rule, if any, would be necessary to integrate the BPCA and the pediatric rule more effectively? see below
2. How would the criteria used by NIH and FDA under section 3 of the BPCA to request studies of already approved drugs relate to the standards promulgated in the pediatric rule and described in 21 CFR 201.23, 314.55, and 601.27 for requiring pediatric labeling for certain drugs and biological products? Which criteria are more appropriate for determining when studies are conducted? see below
3. What provisions, if any, of the BPCA could apply to biological products regulated under section 351 of the PHSA? see below
4. How does the provision in section 3 of the BPCA providing for a recommendation for a formulation change relate to the pediatric rule provision stating that in certain cases a sponsor may be required to develop a pediatric formulation? Should pediatric formulations be required in certain cases? see below
5. General Comments Paula Botstein M.D. Phone 718-499-9729 Botstein Associates 718-832-0992 544 Fourth Street Fax 718-832-1473 Brooklyn, NY 11215 qqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqqq July 5, 2002 Docket No. 02N-0152 21 CFR Parts 201, 312, 314, and 601 ANPR Obtaining timely pediatric studies of and adequate labeling for human drugs and biologics Dockets Management Branch (HFA 305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Submitted electronically to Dear FDA people: FDA’s 1998 pediatric rule is a strong mechanism for ensuring that medicines are studied for children. This rule provides the long-term solution to drugs’ not having adequate instructions for use in children. This pediatric rule should not be weakened nor its scope reduced. The pediatric rule calls for medicines to be studied in children. Children get sick and need medicines, just as adults do. Although most disorders and diseases of children respond to the same medicines effective in adults, doses appropriate for children can only be determined through pediatric studies. Inappropriate dosing leads to lack of effectiveness or to toxicity. Figuring out suitable doses for the pediatric population may be simple or difficult, depending on the drug, but cannot be adequately done by an individual doctor using guesswork when faced with a sick patient. Clinical trials, which may consist of pharmacokinetic studies, are the answer. In addition, safety problems need to be evaluated or basic studies of the effectiveness of some uses of drugs need to be conducted for some drugs in children. The pediatric rule and the Best Pharmaceuticals for Children Act (BPCA) are complementary and are both needed. This rule should not be changed because of the subsequent passage of the 2002 BPCA. Congress passed the BPCA in 2002 while leaving unaffected the 1998 FDA regulations known as the pediatric rule. Congress did not intend that FDA weaken the pediatric rule. Benefits of the pediatric rule A major benefit of the rule is that it kicks in early during a drug’s development. The pediatric rule positions discussion and planning for studying a drug in children into early drug development by requiring that a sponsor’s plans for pediatric study be discussed at routine drug development meetings with the FDA. Consideration of pediatric data and needs thus has become an intrinsic part of drug development. The pediatric rule is obligatory on the part of manufacturers, although FDA can waive or delay its provisions when scientifically appropriate for a particular drug. Under the pediatric rule, FDA may require a manufacturer to develop a pediatric formulation; this provision means that formulations usable in children, such as liquids for toddlers, will thus be available. This provision of the regulation is essential. Results from the rule occur when a drug is approved or soon thereafter: around the time a drug is available for use by pediatric patients and labeling for sensible pediatric use is wanted. Provisions of the pediatric rule applying to already-marketed drugs will be important particularly in those rare cases where pediatric use of an inadequately labeled drug presents potential or demonstrated serious problems of safety or inadequate effectiveness. Limitations of the BPCA The BPCA and its precursor FDAMA create a financial incentive, a period of additional marketing exclusivity in return for a manufacturer’s obtaining pediatric data. This financial incentive is valuable and has resulted in pediatric studies by those companies wishing to avail themselves of the opportunity. However, the BPCA is voluntary and sponsors will not use it for many drugs, as was the case with the FDAMA. The BPCA will preferentially be used for drugs with enormous profits from adult use. These drugs may not include those most needed for use in children. Manufacturers may wait to obtain the marketing exclusivity offered by the BPCA until near the end of a drug’s existing marketing exclusivity; as a result, a sponsor may delay pediatric studies until the drug has been marketed and used in children without labeling information for fifteen years or more. Support for pediatric rule I had a hand in the creation of the pediatric rule and in the implementation of FDAMA, while I worked in FDA’s Center for Drug Evaluation and Research. The proposed pediatric rule generated unusually widespread and enthusiastic comment from many medical groups, patient groups, and others. In addition, many people outside the FDA or outside of CDER and CBER at the FDA expressed surprise that medicines were not already routinely assessed in children. Parents, aunts, uncles, grandparents and those who for other reasons care about the welfare of children viewed requiring pediatric studies of drugs as a real contribution to the health of children. FDA should now fully implement and support its pediatric rule: the rule offers the long-term promise of drugs adequately labeled for use in millions of children. Paula Botstein M.D.

EC -61