Statistical methodology for the comparative assessment of quality attributes in drug development - Scientific guideline

The reflection paper provides current regulatory considerations regarding statistical aspects for the comparative assessment of quality attributes in the settings of pre- and post-manufacturing change, biosimilar development as well as generics development. It raises open issues from a methodological perspective addressing questions related to comparison objectives, sampling strategies, sources of variability, acceptance ranges and statistical analysis approaches to conclude on the similarity of two drug products based on quality attribute data. A main objective of the reflection paper is to establish a framework and a common language to facilitate future discussion among stakeholders and to invite comments in relation to the issues raised.

Keywords: Statistical methodology, comparative assessment, quality attributes, drug development, manufacturing changes, biosimilars, generics, dissolution, inferential statistical methods, similarity assessment

Current version

Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development

AdoptedReference Number: EMA/CHMP/138502/2017

Document history

Implementation of comments received on 'Draft reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development'

Reference Number: EMA/CHMP/310801/2021

Draft reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development

Consultation dates: 01/04/2017 to 31/03/2018Draft: consultation closedReference Number: EMA/CHMP/138502/2017Summary:

The reflection paper provides current regulatory considerations regarding statistical aspects for the comparative assessment of quality attributes in the settings of pre- and post-manufacturing change, biosimilar development as well as generics development. It raises open issues from a methodological perspective addressing questions related to comparison objectives, sampling strategies, sources of variability, acceptance ranges and statistical analysis approaches to conclude on the similarity of two drug products based on quality attribute data. A main objective of the reflection paper is to establish a framework and a common language to facilitate future discussion among stakeholders and to invite comments in relation to the issues raised.

Draft concept paper on the need for a reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development

Consultation dates: 28/06/2013 to 30/09/2013Draft: consultation closedReference Number: EMA/CHMP/297149/2013 Rev. 1Summary:

In the recent past, several requests submitted for scientific advice contained questions concerning the adequacy of planned inferential statistical approaches to compare quality attributes of a (candidate) biosimilar product to that of a reference medicinal product, or of a particular biological drug compound in versions pre- and post-manufacturing changes. For comparative purposes, several different methodological approaches had been proposed to define comparability (‘acceptance’) ranges as well as ‘similarity’ criteria, mostly based on information on batch-to-batch variability. The reflection paper to be prepared will try to reflect on (the limitations of) comparison techniques proposed in the past, but will also try to come up with alternative approaches for the evaluation of ‘similarity/equivalence’ in quality attributes.