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EMA opens public consultation on ICH E11(R1) Guideline

On 13 October 2016, the European Medicines Agency (“EMA”) opened for public consultation the Guideline concerning clinical investigation of medicinal products in the paediatric population, which has been revised to include a new addendum (“R1”). The public consultation opened following the approval of this draft guideline by the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (“ICH”) in September 2016. The consultation deadline for the draft Guideline is 13 April 2017.


The new addendum to the Guideline substantially updates the ICH E11 Guideline which was initially published in 2000. It does not however alter the scope of the original guideline.

With the revision, EMA seeks to update the document to reflect current advances in paediatric drug development, taking into account the regulatory and scientific developments relevant to pediatric populations over the past 16 years. The addendum R1 to the ICH E11 Guideline also aims to harmonize the substantial differences that exist among regions in relation to the acceptance of data generated in paediatric global drug development programs. It recommends the adoption of a common scientific approach to ensure efficient drug development and timely access to medicines for children.

Different approaches to optimise paediatric drug development are set out in the Guideline. In its addendum to the ICH E11 the use of existing knowledge, such as extrapolation and quantitative modelling and simulation techniques is recommended.

ICH E11(R1) is not intended to be comprehensive. Additional details are provided by other ICH guidelines and documents of the World Health Organisation (“WHO”) and paediatric societies.

Ethical considerations

The fundamental principles of paediatric drug development continue to apply. Children should not be enrolled in a clinical study unless necessary to achieve an important paediatric public health need. Experimental interventions or procedures that present greater than low risk must offer sufficient prospects of clinical benefit to justify the exposure of a paediatric population to such risk.

Principles laid down in ICH E11 regarding the parental or legal guardian consent and child assent continue to apply as well. During clinical studies there could be a requirement for obtaining adequate informed consent from paediatric participants once a child reaches the age of legal consent.

Objective and unbiased clinical study results must be publicly available to enhance clinical research, to avoid unnecessary clinical trials especially in children, and to inform clinical decisions in pediatric practice.

Pediatric subgroups and age classification

The EMA provides in its addendum to the ICH E11 Guidance for a rationale to be adopted for the selection of the paediatric population participating in clinical studies.

In addition to chronologic age, factors to be considered in determining the subgroups in paediatric studies should include the following:

  • the physiological development and maturity of organs;
  • the pathophysiology of disease or condition;
  • and the pharmacology of the investigational product.

The EMA also recommends the implementation of a rationale for selection of a neonatal population in clinical studies.

Paediatric formulations

The Guideline emphasises that safety risks may arise where adult dosage forms are used in the paediatric population. To optimise efficacy and reduce the risk for medication and dosing errors, paediatric formulations should include age-appropriate dosage forms, ease of preparations and instructions for use for caregivers, acceptability (e.g., palatability, tablet size), choice and amount of excipients, delivery systems, and appropriate packaging.

ICH E11(R1) provides that planning for development of age-appropriate dosage forms for paediatric populations should be incorporated into the earliest stages of product development. It adds that measures to minimize the impact on dose accuracy, stability and bioavailability must be addressed where manipulations of the available form are unavoidable

For further information visit: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/10/WC500214185.pdf