ICH adopts S11 guideline on nonclinical safety testing for pediatric drugs

The International Council for Harmonisation (ICH) on Tuesday adopted its S11 guideline on nonclinical safety testing to support the development of pediatric drugs following consultations by its regulatory members last year. This guidance is also for products with prior adult use, as well as products being considered for initial human use in paediatrics

ICH says the guideline will encourage “streamlined drug development and higher scientific rigor while minimizing the unnecessary use of animals,” and notes that additional nonclinical investigations should only proceed when there is insufficient previous nonclinical and human data to support the conduct of pediatric studies.

ICH emphasizes that pediatric patients represent a distinct population and face unique safety challenges compared to adults. Immaturity of organ systems and maturation of systems during drug treatment can affect drug pharmacokinetics (PK), pharmacodynamics (DP) and/or off-target effects of pharmaceuticals, potentially leading to differences in safety and/or efficacy profiles.

ICH says that “an understanding of the overall clinical development plan is needed to design an appropriate, efficient nonclinical plan” and weight of evidence (WoE) approach to determine the extent of nonclinical investigations required to support the clinical development of drugs for pediatric population.

“The paediatric clinical development plan for a pharmaceutical is discussed in the ICH E11 guideline and needs to be understood before an appropriate nonclinical plan can be designed” ICH writes.

Under the WoE approach, ICH says sponsors should consider the available clinical data for a treatment, its pharmacological properties, pharmacokinetic data and existing nonclinical safety data. ICH says sponsors should consider the feasibility of additional animal studies, noting that “some endpoints might not be practical in some species.”

The guideline also includes recommendations for the design of nonclinical JAS, pediatric-first/only development and considerations for assessing the safety of excipients and combination drugs for pediatric patients.

Reference: ICH S11 Guideline https://database.ich.org/sites/default/files/S11_Step4_FinalGuideline_2020_0310.pdf