Industry asks FDA to harmonize pediatric study pharmacology guidance with ICH

Regulatory NewsRegulatory News | 12 December 2022 |  By 

Industry groups have asked the US Food and Drug Administration (FDA) to align its recently re-drafted guidance on pediatric clinical pharmacology studies with international guidance, as well as other FDA guidances. The groups also asked for more clarity on several aspects of the guidance.
In September, FDA published a revised draft guidance on pediatric studies that drug and biologic sponsors can use to support their products. Several stakeholders, including the drug industry group PhRMA and Biotechnology Innovation Organization (BIO), wrote to the agency with their recommendations. (RELATED: FDA drafts guidance on pediatric clinical pharmacology studies, Regulatory Focus 8 September 2022)
Both BIO and PhRMA asked FDA to align its guidance with international guidance, including ICH’s E11A guideline on pediatric extrapolation, which reached Step 2 of the ICH process earlier this year.
“PhRMA is supportive of a global regulatory environment that encourages and accelerates the development and review of innovative medicines for pediatric populations,” the group wrote. “To that end, PhRMA notes the importance of FDA’s efforts to facilitate harmonized approaches to pediatric drug development and recommends referencing International Council for Harmonisation (ICH) guidance where appropriate.”
BIO noted that the revised draft guidance doesn’t reference the agency’s draft guidance published earlier this year to improve trial enrollment of participants from underrepresented racial and ethnic backgrounds. The group said it would like to see language in a final guidance that encourages representation of children from underrepresented populations.
“Clinical trials designed to include pediatric participants should also consider adequate representation of children from diverse racial and ethnic backgrounds,” said BIO. “Diverse populations as defined by race and ethnicity are relevant to the evaluation of medical products and there have been some observed correlations between self-reported race, ancestry, genetic variations or ethnicity, and response.”
BIO also said it would like to see a reference to FDA’s 2020 draft guidance on pharmacokinetics and patients with impaired renal function.
While the revised pediatric clinical pharmacology guidance recommends that sponsors use physiologically based pharmacokinetic (PBPK) modeling to evaluate drug-drug interactions, PhRMA and BIO asked for more detail on how to use such methods, including when PBPK modeling can be used beyond exploratory analysis, such as to support clinical study waivers depending on the pediatric age group.
“If a disease is expected to occur in certain segments of the pediatric population as well as adults, it would be helpful if the agency can offer guidance on circumstances where pediatric-inclusive efficacy trials could be initiated with doses selected from PBPK models without a staged approach of conducting pediatric PK studies to establish the dose,” said PhRMA. “This could be incorporated as a safety/PK lead-in with definitive pediatric PK characterization coming from an integrated adult and pediatric population PK analysis based on the totality of data collected across the adult and pediatric population in the efficacy trial.”
Though the draft guidance also includes clinical pharmacology considerations for biologics, PhRMA and BIO noted that there is a lack of information on the pharmacokinetic (PK) characteristics of biologics the agency is looking for. They recommended that FDA update the guidance to include such information.
“Many of the paragraphs describing absorption, distribution, metabolism, and excretion (ADME) processes appear to focus on small molecules,” added PhRMA. “It would be helpful for the draft guidance to address additional factors that can impact distribution/metabolism for large molecules, considering their size and more complex nature.”
PhRMA added that it would like to see a change to the title of the draft guidance to not just address industry but also include other stakeholders, such as clinical investigators and institutional review boards (IRB), who play key roles in furthering pediatric clinical trials.
Several drug companies including Pfizer, Regeneron and Certara also submitted comments to the draft guidance docket, requesting clarifications and recommended changes on topics such as pediatric dose selection, gestational age and risk.


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