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FDA Draft Guidance Clarifies Pediatric Labeling Requirements for Drugs and Biologics

Posted 28 February 2013 | By

The US Food and Drug Administration (FDA) has released a new draft guidance document pertaining to the pediatric information that sponsors and applicants must place within the approved product labeling for human drug and biological products, the second labeling guidance to be released in as many weeks.


In 2006, FDA released a final rule requiring that all pharmaceutical and biological products intended for use in humans be labeled with the pediatric-specific information in accordance with specified formatting.

Those requirements, contained within the Physician Labeling Rule (PLR), were a byproduct of the Pediatric Research Equity Act (PREA) of 2003, which was enacted partly to make sure medicines had (when possible or practical) clear prescribing information for children.

"Specifically, PREA requires applications (or supplements to applications) under section 505 of the FD&C Act or section 351 of the Public Health Service Act (PHSA), respectively, for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration to contain a pediatric assessment, unless the applicant has obtained a waiver or deferral (section 505B(a) of the Federal Food, Drug and Cosmetic Act)," FDA explained.

For the purposes of the PLR, children were defined as those under the age of 17, including neonates, infants, children and some adolescents.

But the 2006 regulation is lengthy and at times confusing, and FDA's 28 February 2013 draft guidance notes that its explicit intent to "help ensure that all useful information on the use of drugs and biological products in the pediatric population (whether positive, negative or inconclusive) is consistently placed in the proper sections within labeling so that the information is clear and accessible to health care providers."

Three Paths: Known Safe/Effective, Unknown and Known Unsafe/Ineffective

While some of the data may be extrapolated from adult studies if the effects of the drug are "sufficiently similar in adults and pediatric patients," this is generally limited only to efficacy data, and not safety or dosing, both of which much be calculated separately. "Because pediatric patients may be more or less prone to drug toxicities based on immaturity or developmental changes, the safety of a drug generally should be studied in pediatric patients directly," the guidance explains.

In addition, data generated regarding the safety or efficacy may be sufficient for all populations, or only sufficient to support safe and effective prescribing in limited pediatric subpopulations. The guidance contains a decision matrix that explains which data would be sufficient to support certain claims, and which would not.

The bulk of the guidance, however, deals with the placement of that data within the product labeling. Per the aforementioned decision matrix, sponsors are required to indicate whether the pediatric findings about their product are positive, negative or inconclusive, and place those findings within the "Pediatric Use" subsection of the labeling.

Limited Off-Label Labeling

That information must be "clear and accessible to health care providers and should describe what is known and unknown about use of the drug in the pediatric population and must highlight any differences in effectiveness or safety in the pediatric population versus the adult population," FDA explained.

For example, if a pediatric indication is not supported by the collected data, sponsors must include a statement on the label that safety and effectiveness have not been established. In those cases, sponsors can include information regarding the clinical trials, dosing and pharmacokinetic information to promote safer prescribing, but must take care to note that this information is only for use in specific subpopulations "to avoid the impression that the drug has an approved pediatric use," FDA said. Otherwise, it risks being misbranded due to marketing for an unapproved use.

Any waived studies, either due to efficacy or safety concerns, must also be noted on the label.

For data that does show safe and effective prescribing, however, the sponsor much include that data on the labeling, including indications and usage, dosage and administration, contraindications, warnings and precautions, adverse reactions, use in specific pediatric subpopulations (and associated limitations), clinical pharmacology, pediatric clinical studies and patient counseling information.

All of that information must be specifically tailored to pediatric subpopulations, and is not simply a recitation of the adult information contained elsewhere on the label.

Comments on the draft guidance are due by 29 April 2013.

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