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ICH E6(R3) proactive quality
Last updated September 2026

Quality by Design (QbD) Training

Learn how ICH E6(R3) advances proactive quality by design: identify Critical to Quality factors, assess meaningful risks, and build proportionate controls into the trial plan.
See the planning framework

Working definition

Quality by Design (QbD) is a proactive approach to trial design that identifies Critical to Quality (CtQ) factors during protocol development and builds protective systems before problems can occur. This approach is supported by ICH E6(R3).

Quality built in
Design
Factor focused
CtQ
Verifiable record
Free

Foundation

What is quality by design?

Quality by Design (QbD) is a proactive approach that emphasizes designing quality into clinical trials from the beginning, rather than attempting to test for it at the end. ICH E6(R3) advances this approach through its quality-by-design and proportionality principles.

The QbD philosophy

“Quality should be built into the scientific and operational design and conduct of clinical trials.”

ICH E6(R3) Good Clinical Practice, Principle 6

Core QbD principles

01

Purpose-Driven

Predefined quality objectives

Before starting any trial, clearly define what 'quality' means in your specific context. What outcomes are essential for participant safety? What data must be reliable? These objectives guide all downstream decisions.

02

Prevention-First

A prospective approach

QbD is fundamentally forward-looking. Rather than reacting to problems after they occur, you anticipate risks during design and build preventive measures into processes from the start.

03

CtQ-Centered

Critical to quality focus

Not everything is equally important. QbD starts by identifying Critical to Quality (CtQ) factors: the trial attributes fundamental to participant protection, reliable and interpretable results, and decisions based on those results.

04

Tailored

Fit-for-purpose design

Every element of the trial, from CRF design to monitoring intensity, should be designed on purpose to support the quality objectives. There is no one-size-fits-all approach.

05

Methodical

Systematic planning

QbD involves structured, documented planning processes. Risk assessments, quality plans, and design decisions should follow a systematic methodology, not ad hoc choices.

06

Inherent Quality

Quality built in, not added

Quality cannot be 'inspected in' after the fact. It must be designed into the trial from conception. Retrofitting quality controls is expensive and often ineffective.

Approach comparison

QbD compared with traditional quality approaches

AspectTraditional approachQuality by design
TimingQuality checked at the endQuality designed at the start
FocusAll data treated equallyCritical to Quality factors prioritized
ApproachReactive problem-solvingProactive risk prevention
MonitoringBroad, routine retrospective verificationRisk-proportionate, targeted oversight
EfficiencyResource-intensive across all areasResources focused where they matter
How RBQM complements QbD

Implementation

A practical QbD planning framework

This Academy framework translates E6(R3)'s quality-by-design principles into five planning activities. It is a teaching aid, not a regulator-prescribed sequence or a substitute for your organization's quality system.

  1. 01

    Define quality objectives

    Begin by clearly defining what 'quality' means for your specific trial. What outcomes are essential for participant safety? What data is critical for regulatory decision-making?

    Key activities

    • Identify trial-specific quality goals
    • Define success criteria for participant protection
    • Establish data reliability requirements
    • Document quality objectives in planning documents

    Deliverable

    Quality objectives document

  2. 02

    Identify critical to quality factors

    Determine the specific processes, activities, and data that are essential to achieving your quality objectives. These Critical to Quality (CtQ) factors will receive the most attention.

    Key activities

    • Map trial processes to quality objectives
    • Identify data critical for primary endpoints
    • Determine safety-critical processes
    • Prioritize factors by importance and risk

    Deliverable

    CtQ factor list with rationale

  3. 03

    Assess risks to CtQ factors

    For each Critical to Quality factor, prospectively assess what could go wrong. Consider likelihood, impact, and detectability to prioritize your focus areas.

    Key activities

    • Conduct prospective risk assessments
    • Evaluate risks to each CtQ factor
    • Score and prioritize identified risks
    • Document risk assessment methodology

    Deliverable

    Risk assessment documentation

  4. 04

    Design protective controls

    Build quality controls directly into trial design. This includes protocol procedures, CRF design, monitoring strategies, and operational processes, all tailored to protect CtQ factors.

    Key activities

    • Design protocol procedures to protect CtQ factors
    • Create fit-for-purpose data collection tools
    • Plan risk-proportionate monitoring
    • Select vendors with appropriate capabilities

    Deliverable

    Quality-integrated trial design

  5. 05

    Implement and monitor

    Execute the designed quality systems and monitor their effectiveness. Use Key Risk Indicators to detect issues early and adapt controls as needed throughout the trial.

    Key activities

    • Train staff on quality-critical procedures
    • Implement centralized monitoring for KRIs
    • Conduct periodic effectiveness reviews
    • Adapt controls based on emerging data

    Deliverable

    Ongoing quality management

Trial-specific examples

Illustrative critical to quality (CtQ) factors

CtQ factors vary by trial, but typically fall into these categories. Your trial should identify specific factors based on protocol complexity, population, and endpoints.

01

Participant safety

  • Informed consent process integrity
  • Eligibility verification procedures
  • Serious adverse event detection and reporting
  • Investigational product accountability
02

Data reliability

  • Primary endpoint data collection
  • Source document accuracy
  • Data entry and verification processes
  • Laboratory sample handling
03

Regulatory compliance

  • Protocol adherence for critical procedures
  • Essential document maintenance
  • GCP training documentation
  • IRB/EC approval processes
How to identify CtQ factors

QbD FAQs

Common questions about quality by design

The fundamentals, and how they play out in practice.

What is Quality by Design (QbD) in clinical trials?
Quality by Design (QbD) is a proactive approach that builds quality into the scientific and operational design of a clinical trial. It starts by identifying trial-specific Critical to Quality (CtQ) factors, then designing proportionate processes and controls around the risks that could meaningfully affect those factors.
How does Quality by Design relate to ICH E6(R3)?
ICH E6(R3) Principle 6 says quality should be built into the scientific and operational design and conduct of trials, with Critical to Quality factors identified prospectively. Section 3.10 recommends that sponsors adopt a proportionate, risk-based quality approach that incorporates quality into trial design. FDA publishes E6(R3) as nonbinding guidance; applicable statutes and regulations supply legally enforceable duties.
What is the relationship between QbD and RBQM?
Quality by Design (QbD) and Risk-Based Quality Management (RBQM) are complementary approaches that work together. QbD focuses on the planning phase: designing quality into the trial before it starts by identifying Critical to Quality factors and building protective processes. RBQM is the ongoing framework for managing risks to those CtQ factors for the rest of the trial. QbD is prevention by design; RBQM is the continuous management that follows.
What are the key elements of Quality by Design?
Key elements of QbD include: (1) predefined quality objectives, a clear definition of what quality means for your trial; (2) Critical to Quality factor identification, determining which processes and data are essential; (3) prospective risk assessment, anticipating problems before they occur; (4) quality-focused protocol design, building protective measures into procedures; (5) fit-for-purpose data collection, designing CRFs and systems around the quality needs; (6) systematic planning documentation.
When should Quality by Design activities occur?
QbD begins during trial planning and protocol development, before conduct starts, and continues as emerging information changes the risk picture. Early decisions include identifying trial-specific CtQ factors, designing fit-for-purpose data collection, and planning controls and monitoring proportionate to identified risks.
What are Critical to Quality (CtQ) factors?
Critical to Quality (CtQ) factors are the processes, data points, and activities that are essential to participant protection and reliable trial results. Examples include informed consent processes, eligibility verification, primary endpoint data collection, serious adverse event reporting, and investigational product accountability. CtQ factors vary by trial based on design complexity, patient population, therapeutic area, and primary endpoints. Identifying CtQ factors is the foundation of both QbD and RBQM.
How does QbD differ from traditional quality approaches?
QbD shifts attention upstream from broad retrospective checking to prospective design. Teams identify what is critical, anticipate risks to those factors, and build proportionate controls into the protocol, data flow, and operating plan. Verification and monitoring remain important, but their scope is informed by the trial's risks rather than a universal percentage.
What should QbD documentation make clear?
Documentation should make the trial's quality reasoning traceable: which factors are critical to quality, which risks could affect them, which controls were selected, how monitoring is tailored, and how emerging information changes the approach. The exact documents and approvals depend on applicable law, the protocol, contracts, and the organization's quality system.
Is QbD training included in MyTrial Academy's free course?
Yes, Quality by Design training is included in our free ICH E6(R3) GCP course. Module 4 covers Quality by Design, Critical to Quality factors, proportionality, protocol requirements, and a practical RBQM framework. You'll receive a free verifiable completion record; the printable PDF certificate is a separate, optional purchase.
How do I implement QbD in my organization?
Make sure the team understands the principles first, then: (1) Begin identifying CtQ factors early in protocol development; (2) Document quality objectives before finalizing the protocol; (3) Conduct prospective risk assessments tied to CtQ factors; (4) Design protocol procedures to protect CtQ factors; (5) Create fit-for-purpose data collection tools; (6) Plan monitoring strategy based on identified risks; (7) Review and adapt throughout the trial lifecycle.

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