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. 2021 Mar;55(2):251-261.
doi: 10.1007/s43441-020-00209-0. Epub 2020 Sep 3.

Quality Tolerance Limits: Framework for Successful Implementation in Clinical Development

Ruma Bhagat  1 , Lukasz Bojarski  2 , Soazig Chevalier  3 , Dagmar R Görtz  4 , Stéphanie Le Meignen  5 , Marcin Makowski  6 , Patrick Nadolny  7 , Marion Pillwein  8 , Melissa Suprin  9 , Sabine Turri  10
Affiliations

Quality Tolerance Limits: Framework for Successful Implementation in Clinical Development

Ruma Bhagat et al. Ther Innov Regul Sci. 2021 Mar.

Abstract

The International Council for Harmonisation (ICH) E6(R2) (International Council for Harmonisation (ICH). ICH harmonised guideline: integrated addendum to ICH E6(R1): guideline for good clinical practice E6(R2). 2016. https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf . Accessed 5 Dec 2019) introduced Quality Tolerance Limits (QTLs) to the industry, and in doing so, modernized quality control for clinical trials. QTLs provide measured feedback on clinical trial parameters previously only used by statistical and clinical functions to track trial progress toward endpoints. Elevating these measures as part of the Quality Management System (QMS) provides greater visibility across clinical trial functions and the enterprise as well as to measures that are important indicators of the state of participant protection and reliability of trial results. In support of this new requirement, TransCelerate developed a framework to guide industry sponsors and their agents in implementing QTLs. This QTL Framework is intended to aid industry's ability to improve the quality of clinical research through the implementation of QTLs in a way that helps protect trial participants and reliability of trial results while meeting Health Authority (HA) expectations. The framework is intended to maximize efficiency and minimize confusion in the implementation of QTLs. The framework includes proposed approaches for implementation of QTLs for a clinical trial as defined in Section 5.0.4 and 5.0.7 of ICH E6(R2) (International Council for Harmonisation (ICH). ICH harmonised guideline: integrated addendum to ICH E6(R1): guideline for good clinical practice E6(R2). 2016. https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf . Accessed 5 Dec 2019) and considerations for setting thresholds.

Keywords: KRI; Key risk indicators; QMS; QTL; Quality management system; Quality tolerance limits.

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Conflict of interest statement

The authors declare that they have no conflicts of interest. However, all authors are employees and/or stockholders of the companies with which they are affiliated.

Figures

Fig. 1
Fig. 1
Risk-Based Quality Management Components. CSR Clinical Study Report; QTL Quality Tolerance Limit
Fig. 2
Fig. 2
Quality Tolerance Limit (QTL) Framework—Process Overview.
Fig. 3
Fig. 3
Define QTLs Process Map.
Fig. 4
Fig. 4
Monitor QTLs Process Map.
Fig. 5
Fig. 5
Report on QTL Process Map.
See this image and copyright information in PMC

References

    1. International Council for Harmonisation (ICH). ICH harmonised guideline: integrated addendum to ICH E6(R1): guideline for good clinical practice E6(R2). 2016. https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf. Accessed 5 Dec 2019.
    1. Risk-based quality management: quality tolerance limits and risk reporting. TransCelerate website. https://www.transceleratebiopharmainc.com/wp-content/uploads/2017/09/Ris.... Published 2017. Accessed 5 Dec 2019.
    1. International Council for Harmonisation (ICH). ICH harmonised guideline: general considerations for clinical studies E8(R1). Draft version endorsed on May 8, 2019. https://database.ich.org/sites/default/files/E8-R1_EWG_Draft_Guideline.pdf. Accessed 5 Dec 2019.
    1. Suprin M, Chow A, Pillwein M, et al. Quality risk management framework: guidance for successful implementation of risk management in clinical development. Ther Innov Regul Sci. 2019;53:36–44. doi: 10.1177/2168479018817752. - DOI - PubMed
    1. https://www.ctti-clinicaltrials.org/files/principles_document_finaldraft...