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June 10, 2020 Regulatory Affairs

Pediatric Labeling Best Practices


A large percentage of drugs are used off-label in pediatric patients. Unfortunately, when a patient uses a drug off-label, the drug is being used without FDA approval, which might result in inadequate therapeutic effect or actual harm. The patient potentially could be under or overdosed, which raises both efficacy and safety issues.

For this reason, the FDA has established two pediatric drug development laws. The first law is the Best Pharmaceuticals for Children Act (BPCA). It provides an incentive for Sponsors to conduct FDA-requested pediatric studies by granting an additional six months of marketing exclusivity.

The second law is the Pediatric Research Equity Act (PREA), which requires Sponsors to study investigational drugs in children under certain circumstances. Both the BPCA and PREA were made permanent in 2012 with the passage of the Food and Drug Administration Safety and Innovation Act (FDASIA).

To help Sponsors navigate these two laws during the pediatric drug development process, the FDA issued an updated guidance in March of 2019 entitled Pediatric Information Incorporated Into Human Prescription Drug and Biological Product Labeling.

The goal of this guidance document is to ensure that Sponsors consistently place information on the use of prescription drugs in pediatric populations in the proper sections and subsections within the labeling, whether that information is positive, negative, or inconclusive. The intent is that the information is clear and accessible to health care providers.

According to the guidance, pediatric information should be discussed in the Pediatric Use subsection and included in other sections of labeling as appropriate. The document presents four scenarios and gives direction as to the suggested content of the pediatric use information.

In the first scenario, there is evidence that supports safety and effectiveness of a drug for an indication in pediatric patients. Consequently, all approved pediatric indications should be included in the Indications and Usage section. The language should read, “Drug X is indicated for the treatment of Indication Y in adult and pediatric patients” or “Drug X is indicated for the treatment of Indication Y in adults and pediatric patients aged A and older.”

The Dosage and Administration section must include the recommended dosage in pediatric patients for all approved pediatric indications. This section must also include preparation and administration instructions relating to pediatric use as well as information regarding the storage conditions for stability of the prepared drug.

The Adverse Reactions section must include details of pediatric adverse reaction data from clinical studies or post-marketing data. Sponsors should highlight adverse reactions that are novel or unique in pediatric patients or take place at a greater or lesser frequency or severity than in adults.

The Pediatric Use subsection must include a pediatric use statement when a drug is approved in pediatric patients for an indication that is the same as an approved indication in adults. Generally, this statement should be the first sentence in the section. The statement might read, “The safety and effectiveness of DRUG X (for Indication Y) have been established in pediatric patients aged A years and older.”

The Clinical Pharmacology section must provide detailed descriptions of pediatric pharmacokinetic, pharmacodynamic, and/or pharmacogenomic study data, relevant data obtained from modeling, simulation, or bridging studies, and dose-response information.

The Clinical Studies section must contain a detailed description of studies that provide substantial evidence of effectiveness for use in pediatric patients or populations.

In the second scenario, evidence does not support safety and effectiveness of a dose for an indication in pediatric patients. When this is the case, relevant information related to the unapproved use that is included in labeling should be placed only in the Pediatric Use subsection.

The language might read, “The safety and effectiveness of DRUG X have not been established in pediatric patients (for Indication Y). Effectiveness was not demonstrated in two adequate and well-controlled studies conducted in 120 DRUG X-treated pediatric patients, aged A to younger than B years for Indication Y.”

In the third scenario, there is no evidence to support safety and effectiveness of a drug for an indication in pediatric patients. The reason could be that studies have not been conducted or are ongoing. In this scenario, an appropriate pediatric use statement must be placed in the Pediatric Use subsection. The language might read, “The safety and effectiveness of DRUG X have not been established in pediatric patients younger than A years old.”

In the fourth scenario, the drug is contraindicated for use in pediatric patients. Under this scenario, the contraindication and the reason for the contraindication should be stated first in the Pediatric Use subsection as well as in the Contraindications section. The language might read, “Drug X is contraindicated in pediatric patients because of deaths observed in a juvenile animal study with administration of the drug to juvenile rats at clinically relevant doses.”

Although the guidance document gives excellent explanations and detailed language examples, it helps to have a consultant on your team that understands the guidance and the underlying laws and situations to which it applies. You can count on ProPharma Group for assistance with applying best practices to the labeling of your pediatric drug products.  To learn more about our services and how we can help you, contact us today.


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