FDA issues final guidance on pediatric anti-infective development
The US Food and Drug Administration (FDA) on Thursday issued a final guidance to assist sponsors in developing anti-infective drugs for the pediatric population. The guidance revises the draft version by providing more information on safety data collection and juvenile toxicity studies.
The guidance provides recommendations for developing anti-infective drugs, including antibacterials, antifungals, and antiparasitic products, for pediatric populations.
A draft guidance was issued in June 2020. (RELATED: Pediatric anti-infective development addressed by FDA, Regulatory Focus, 29 June 2020).
The guidance notes some of the challenges in pediatric drug development, including development changes in neonates and young children which can affect drug absorption and distribution. In addition, there is limited ability to collect samples for testingfrom sources such as blood and cerebrospinal fluid from this population.
The guidance discusses methods for extrapolating efficacy data from adult studies, how to collect and analyze safety data, and criteria for conducting juvenile toxicology studies for pediatric populations.
The agency also encourages sponsors to meet with them early on to discuss initial pediatric study plans (iPSPs), generally no later than 60 days after the end-of-phase 2 meetings.
The guidance also refers sponsors to International Council on Harmonization (ICH) guidelines covering nonclinical safety testing to support the development of pediatric pharmaceuticals, including the S11 guideline on Nonclinical Safety Testing in Support of Development of Pediatric Pharmaceuticals, the M3(R2) guideline Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorizations for Pharmaceuticalsand FDA’s guidance Nonclinical Safety Evaluation of Pediatric Drug Products.
For cell and gene therapy products, the agency recommends sponsors consult its guidance titled Preclinical Assessment of Investigational Cellular and Gene Therapy Products.
More development considerations
The guidance offers additional considerations for safety data needed to support the development of anti-infectives for this population.
Developers can use safety data from non-clinical studiesand the adult population to aid in identifying adverse events of interest in pediatric patients, it adds that “certain toxicities may affect developmentally immature organ system and tissues that are unique to the pediatric population, with increasing risk likely with decreasing age. These situations may merit additional safety assessments.”
The finalized version also offers more examples of when FDA may recommend juvenile toxicology studies, such as when “there are insufficient data from prior clinical experience, or safety concerns cannot be adequately addressed in other nonclinical studies” and the drug is primarily intended for the pediatric population.
FDA incorporates comments
FDA incorporated a comment from the Biotechnology Industry Organization (BIO) to specify that the scope of the guidance to include antibacterial, antifungals and antivirals. The original guidance did not include this clarification.
The Global Antibiotics Research and Development Partnership (GARDP) had asked FDA to include more information on how to address the use of anti-infectives in neonates, since these medicines are “an important class of drugs in this population.”
The guidance, in wording carried forward from the draft, says that more detailed information on clinical pharmacology considerations for neonates, such as sample sizes, pharmacokinetic sampling and data analysis, can be found in several other FDA guidances, including General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products and its General Considerations for Pediatric Studies for Drugs and Biological Products.
Final guidance
Comments on draft guidance
The guidance provides recommendations for developing anti-infective drugs, including antibacterials, antifungals, and antiparasitic products, for pediatric populations.
A draft guidance was issued in June 2020. (RELATED: Pediatric anti-infective development addressed by FDA, Regulatory Focus, 29 June 2020).
The guidance notes some of the challenges in pediatric drug development, including development changes in neonates and young children which can affect drug absorption and distribution. In addition, there is limited ability to collect samples for testingfrom sources such as blood and cerebrospinal fluid from this population.
The guidance discusses methods for extrapolating efficacy data from adult studies, how to collect and analyze safety data, and criteria for conducting juvenile toxicology studies for pediatric populations.
The agency also encourages sponsors to meet with them early on to discuss initial pediatric study plans (iPSPs), generally no later than 60 days after the end-of-phase 2 meetings.
The guidance also refers sponsors to International Council on Harmonization (ICH) guidelines covering nonclinical safety testing to support the development of pediatric pharmaceuticals, including the S11 guideline on Nonclinical Safety Testing in Support of Development of Pediatric Pharmaceuticals, the M3(R2) guideline Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorizations for Pharmaceuticalsand FDA’s guidance Nonclinical Safety Evaluation of Pediatric Drug Products.
For cell and gene therapy products, the agency recommends sponsors consult its guidance titled Preclinical Assessment of Investigational Cellular and Gene Therapy Products.
More development considerations
The guidance offers additional considerations for safety data needed to support the development of anti-infectives for this population.
Developers can use safety data from non-clinical studiesand the adult population to aid in identifying adverse events of interest in pediatric patients, it adds that “certain toxicities may affect developmentally immature organ system and tissues that are unique to the pediatric population, with increasing risk likely with decreasing age. These situations may merit additional safety assessments.”
The finalized version also offers more examples of when FDA may recommend juvenile toxicology studies, such as when “there are insufficient data from prior clinical experience, or safety concerns cannot be adequately addressed in other nonclinical studies” and the drug is primarily intended for the pediatric population.
FDA incorporates comments
FDA incorporated a comment from the Biotechnology Industry Organization (BIO) to specify that the scope of the guidance to include antibacterial, antifungals and antivirals. The original guidance did not include this clarification.
The Global Antibiotics Research and Development Partnership (GARDP) had asked FDA to include more information on how to address the use of anti-infectives in neonates, since these medicines are “an important class of drugs in this population.”
The guidance, in wording carried forward from the draft, says that more detailed information on clinical pharmacology considerations for neonates, such as sample sizes, pharmacokinetic sampling and data analysis, can be found in several other FDA guidances, including General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products and its General Considerations for Pediatric Studies for Drugs and Biological Products.
Final guidance
Comments on draft guidance
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