Regulatory update: Critical to Quality Factors

Critical to Quality Factors refers to a basic set of factors relevant to ensuring clinical study quality. This new term is found in the International Council for Harmonisation (ICH) revised harmonised guideline: General Considerations for Clinical Studies, know more commonly as E8(R1). It is anticipated that E8(R1) will be approved by the ICH early in 2021.

The revised guideline E8(R1) focuses on designing quality into clinical studies, considering the diversity of clinical study designs and data sources used to support regulatory and other health policy decisions. The principles and approaches set out in this guideline, including those of quality by design, should inform the approach taken to the design, conduct, and reporting of clinical studies and the proportionality of control measures (risk mitigation) employed to ensure the integrity of the critical to quality factors.

The Critical to Quality Factors should be identified for each and every study in the planning stages with close attention to those factors that stand out as serious or potentially threatening to study quality. These critical to quality factors are traits of a study whose integrity is fundamental to:

• the protection of study subjects,
• the reliability and interpretability of the study results,
• the decisions made based on the study results.

These quality factors are considered to be ‘critical’ because, if their integrity were to be undermined by errors of design or conduct at the site level, the reliability or ethics of decision-making would also be undermined.

Many of the critical to quality factors may be identified as elements in the Sponsor level and/or Site level Risk Management and Quality Plans.

Annex 3 of the E8(R1) document, provides excellent examples of the key critical to quality factors and matches them with the ICH Guidance that applies.  This helpful table is considered a working document and will be updated as new guidance are added. Annex 3 can be found at the end of the E8R1 document.

References and Links

The new ICH guidelines database and directory is located at https://www.ich.org/page/search-index-ich-guidelines

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH harmonised guideline: General Considerations for Clinical Studies E8(R1). Draft version. Endorsed on 8 May 2019 (expected to be approved early in 2021).

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH harmonised guideline: General Considerations for Clinical Studies E8(R1). Draft version. Annex 3: Selected Examples Of Critical To Quality Factors. Endorsed on 8 May 2019 for updates as new guidances are added.