Utility of Comparative Efficacy Studies in Biosimilar Development

During the ICH Assembly Meeting on 18 and 19 November, the Management Committee approved a number of final documents as well as a concept paper entitled ‘Considerations for the Use of Real-World Evidence (RWE) to Inform Regulatory Decision Making with a focus on Effectiveness of Medicines' and  M18, ‘Framework for Determining the Utility of Comparative Efficacy Studies in Biosimilar Development Programs’, which was also published on the ICH website on 19 November. The content is summarised briefly below.

Type of harmonisation planned

The planned new multidisciplinary guideline M18 is intended to establish criteria and framework conditions for deciding whether comparative efficacy studies (CES) are still necessary in the development of biosimilars. It will also explain the conditions under which such studies can be waived without compromising the assessment of efficacy, safety and immunogenicity. The aim is to create consistent expectations worldwide early in the development planning stage.

Background and problem

Traditionally, CES were routinely expected for the approval of biosimilars. However, growing experience shows that modern analytical methods can detect differences between biosimilars and reference products much more sensitively than clinical efficacy studies. CES therefore often do not provide any additional insights, but require considerable resources and unnecessarily tie up study participants. Numerous studies and new guidelines from various authorities now support the position that CES are generally not necessary. However, differing regulatory requirements in different regions continue to lead to inconsistent approaches.

Objective and content of the guideline

The guideline aims to

• define relevant factors for assessing the scientific benefit of CES within biosimilar development programmes
• create a risk-based framework that describes when CES are necessary and when they are not
• explain how efficacy, safety and immunogenicity can be reliably assessed even without CES
• build on existing ICH Q5E concepts for the comparability of manufacturing changes, but adapt them to the specific context of biosimilar development

Expected outcome

The guideline aims to establish a harmonised, scientifically sound approach to clearly determine the need for CES. This should make the development of biosimilars more efficient, create regulatory planning security and avoid unnecessary studies.

Organisation and timetable

An Expert Working Group (EWG) with experts from the fields of quality, analytics, clinical evaluation and pharmacology will carry out the project. A draft version is expected within 18 months, with the complete guideline to be completed within three years.