How to implement ICH Q8–Q9–Q10–Q12: operational guide

Introduction

Applying ICH Q8–Q12 isn't just about theory: it's about transforming decisions, processes, and controls on a daily basis. This guide takes GMP teams on a practical, step-by-step journey from product design to lifecycle change management.

Step 1: Set up QTPP (Q8)

Operational activities:

1. Define the intended use of the product
2. Identify critical parameters (stability, dissolution, purity)
3. Link each parameter to patient risks
   Output: Complete QTPP approved by the cross-function team.

Step 2: Identify CQAs and critical variables

Using QRM tools:

• Ishikawa to map potential sources of variability
• FMEA to classify impact on safety/efficacy
• DOE screening to analyze variable–CQA relationships
  Output: CQAs table + criticality ranking.

Step 3: Create the Design Space

Technical activities:

• Perform DOE
• Modeling process parameters
• Define acceptable multidimensional ranges
• Documenting scientific knowledge
  Output: design space ready for the dossier.

Step 4: Risk-based control strategy

Comprehends:

• IPC and PAT
• Continuous process monitoring
• Real Time Release Testing where applicable
• Trend analysis
  Output: Control Strategy integrated into the PQS.

Step 5: Integrate QRM into PQS (Q9 + Q10)

To be implemented in:

• Deviation & CAPA
• Change Control
• Suppliers
• Validations
• PQR
  Goal: Every decision must have a documented risk rationale.

Step 6: Lifecycle Management (Q12)

Operationally:

• Define Established Conditions (ECs)
• Compile PLCM Document
• Creating PACMPs for complex changes
• Align RA–QA–Manufacturing
  Output: more predictable and faster change process.

❗ Be careful of…

• Underestimating the importance of QTPP
• Making FMEAs too generic
• Lack of connection between development and commercial
• Presenting design space without solid data
• Change control without QRM attached

🛠️ How to handle a non-conformity

1. Identify event and potential impact on CQA
2. Apply proportionate QRM tool
3. Determine residual risk
4. Choose corrective + preventive CAPA
5. Verify the effectiveness of CAPA
6. Update QRM document if necessary

🧩 GMP Best Practices

• Document every intake
• Preferring real data to just expert opinion
• Involving QA early on
• Use PAT and continuous analysis to reduce final testing
• Creating a single repository of knowledge Q8–Q9–Q10

✔️ Brief operational checklist

• QTPP defined
• Mapped CQAs
• FMEA completed
• DOE conducted
• Documented Design Space
• Control Strategy approved
• QRM integrated into PQS
• PLCM compiled

Realistic use case

A company introduces a new API provider.
Without QRM → frequent deviations, slow variations.
With QRM + Q12 → risk assessed, API parameters compared with CQAs, additional control introduced, change managed quickly via PACMP.

Conclusion

Implementing Q8–Q12 operationally means bringing robustness, speed, and quality to every phase of the lifecycle. Learn more with the complete guide on GuideGxP.com