Table 1.
QbD implementation workflow: from Quality Target Product Profile (QTPP) to control strategy.
| Stage | Description | Key Outputs | Applications/Notes |
|---|---|---|---|
| 1. Define QTPP | Establish a prospectively defined summary of the drug product’s quality characteristics. | QTPP document listing target attributes (e.g., dosage form, pharmacokinetics, stability). | Serves as the foundation for all subsequent QbD steps (ICH Q8). |
| 2. Identify CQAs | Link product quality attributes to safety/efficacy using risk assessment and prior knowledge. | Prioritized CQAs list (e.g., assay potency, impurity levels, dissolution rate). | CQAs vary by product type (e.g., glycosylation for biologics vs. polymorphism for small molecules). |
| 3. Risk Assessment | Systematic evaluation of material attributes and process parameters impacting CQAs. | Risk assessment report, identification of CPPs and CMAs. | Tools: Ishikawa diagrams, FMEA. Focus on high-risk factors (e.g., raw material variability). |
| 4. Design of Experiments (DoE) | Statistically optimize process parameters and material attributes through multivariate studies. | Predictive models, optimized ranges for CPPs and CMAs. | Enables identification of interactions between variables (e.g., mixing speed vs. temperature). |
| 5. Establish Design Space | Define the multidimensional combination of input variables ensuring product quality. | Validated design space model with proven acceptable ranges (PARs). | Regulatory flexibility: Changes within design space do not require re-approval (ICH Q8). |
| 6. Develop Control Strategy | Implement monitoring and control systems to ensure process robustness and quality. | Control strategy document (e.g., in-process controls, real-time release testing, PAT). | Combines procedural controls (e.g., SOPs) and analytical tools (e.g., NIR spectroscopy). |
| 7. Continuous Improvement | Monitor process performance and update strategies using lifecycle data. | Updated design space, refined control plans, reduced variability. | Tools: Statistical process control (SPC), Six Sigma, PDCA cycles. |
Abbreviations: QbD (Quality by Design), QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes), CPPs (Critical Process Parameters), CMAs (Critical Material Attributes), PAT (Process Analytical Technology), ICH (International Council for Harmonisation), FMEA (Failure Mode and Effects Analysis), PDCA (Plan-Do-Check-Act). Regulatory alignment: stages align with ICH Q8 (Pharmaceutical Development). Workflow logic: QbD emphasizes proactive quality assurance, transitioning from empirical batch testing to science-based, data-driven decision-making.