RAPS is closely monitoring developments in the Coronavirus (COVID-19) outbreak. See our public safety page for the latest updates.

The RAPS store will be under maintenance Saturday, 13 June between 6 AM and 12 PM EST. Store functionality may be unavailable at times during this window.
We apologize for any inconvenience caused during this time.

Regulatory Focus™ > News Articles > 2019 > 4 > Industry Groups Call for Changes to ICH S11 Guideline

Industry Groups Call for Changes to ICH S11 Guideline

Posted 23 April 2019 | By Michael Mezher 

Industry Groups Call for Changes to ICH S11 Guideline

Industry groups are calling for changes to a recently released International Council for Harmonisation (ICH) S11 draft guideline on nonclinical safety testing to support the development of pediatric drugs in response to the European Medicines Agency’s (EMA) public consultation on the guideline.
The goal of the guideline is to create a harmonized approach to nonclinical pediatric safety testing across ICH regions and reduce the need for juvenile animal studies (JAS) according to the 3R (replace, reduce and refine) principles.
In comments submitted to EMA, the International Council on Animal Protection in Pharmaceutical Programs (ICAPPP) takes issue with the guideline for not providing enough examples and guidance on nonclinical testing methods besides JAS.
“We urge against JAS studies being performed as a ‘tick-box’ exercise or default option for addressing safety concerns,” ICAPPP writes. Instead, the group argues that a new section should be added discussing in vitro and ex vivo test methods that could be done in lieu of JAS.
ICAPPP also points to research calling into question how reliable or applicable data from JAS are for predicting safety issues in the pediatric population.
“If data from human adults is not enough to predict safety in human children, it is difficult to see how extrapolation of data from young animals to young humans can be meaningful, especially considering the vast species differences that must be accounted for,” ICAPPP writes.
In its comments, the European Federation of Pharmaceutical Industries and Associations (EFPIA) calls for a more tailored approach to JAS when such studies are needed.
“This draft guideline recommends a core set of endpoints for all JAS, even if those endpoints are not focused on the concerns raised in the [weight of evidence] WOE assessment,” EFPIA writes.
While EFPIA agrees that this approach makes sense in situations where there is a lack of understanding of a drug’s pharmacology, the group argues that in situations where a JAS is needed to address specific concerns that all the core endpoints are not needed.
EFPIA also points out that the guideline focuses on whether JAS are needed to support pediatric trials but does not address situations where JAS are conducted concurrently with or after clinical trials.
Members of the European Paediatric Translational Research Infrastructure (EPTRI) commented that they would like to see more harmonization around the data elements used in preclinical studies, which the organization argues would make meta-analyses more feasible and reduce the need for redundant testing.
“In our opinion, in order to optimize future efficacy and safety testing according to the 3R principles, and to increase the effectiveness of developmental studies, common data elements (CDEs) must be set and provided. The use of both core CDEs forms, and forms for CDEs specifically tailored for developmental studies might help to standardize study design and make studies more transparent and cost/time-effective,” EPTRI says.
EPTRI also recommends a change to the figure presenting WOE factors that appears in the guideline, which is intended to help sponsors determine whether further nonclinical studies are warranted.
According to the guideline, the youngest intended patient age for a therapy is one of the most important factors in determining whether further studies are required. However, EPTRI says the guideline’s approach is flawed, as it depicts a scale showing that further studies are less likely to be needed if the youngest intended patient age is 12 or older.
“Numerous experimental studies on behavioral toxicity in developing animals identify indeed the adolescence as another critical developmental period, with increased risk for adverse drug effects,” EPTRI writes, recommending instead that the scale range from neonates all the way to patients 18 years of age.
EMA, Comments

Regulatory Focus newsletters

All the biggest regulatory news and happenings.