Quality Tolerance Limits

Project Scope

Define role of QTLs in QbD, in particular the relationship to CTQs (Critical to Quality Factors), Estimands and continuous quality improvement (CQI)
Discuss the use of QTLs in Early Development/small studies, bio equivalence and complex designs
Discuss examples of how to define QTLs, different methodologies and different parameters in use across the industry
Discuss difficulties and challenges of implementation of QTLs
Examine role of QTLs as part of the of the lessons learned (RCA) feedback loop

Project Leads	Email
Chris Wells, Roche	chris.wells.cw1@roche.com
Mireille Lovejoy, GE Healthcare	mireille.lovejoy@gehealthcare.com
Alex Pearce, PHUSE Project Assistant	alexandra@phuse.global

CURRENT STATUS Q4 2023
Continuing to work on their White Paper

Objectives & Deliverables	Timelines
Release of draft White Paper	Q3 2022
Publish White Paper	Q3 2023

Deliverables
Assessing the Use of Quality Tolerance Limits in the Pharmaceutical Industry.

Problem Statement

QTLs - the role they play in defining quality within the QbD framework, their relationship to Critical to Quality factors, associated methodologies and the interpretation of them have not been fully defined in clinical development, in particular where early development/small studies, bio equivalence studies and complex designs are concerned.

Problem Impact

This will impact the whole clinical development process and allow the move away from perfection to a defined and achievable quality, from which continuous quality improvement can begin.

Terminology Example:

Target Product Profile (TPP)
- Patient wants extended dosing from current BD product on market
Critical Quality Attribute (CQA)
- Once a day dosing
Critical to Quality Factor (CTQ)
- In early stage trials drug levels shown at 24 hours
- In Phase 2-3 demonstrate efficacy
Quality Tolerance Limit
- Pre-define what will be acceptable limits for acceptance
  - These QTL's will change at different stages