GB/T 36036-2018 in English

This standard specifies the full life cycle management requirements for pharmaceutical machinery cleaning and sterilization validation, covering the entire process from validation plan formulation to document archiving. The key points include:

• Quadruple confirmation of verification purpose (Clause 4.1)
• Verification principles based on risk analysis (Clause 4.2)
• Method for determining the scope of verification (Clause 4.3)
• Phase-based verification procedure (Clause 4.4)

The standard requires the establishment of a four-level document system:

1. Validation Master Plan (VMP)
2. Validation Plan (VP)
3. Validation Report (VR)
4. Supporting records (including:
   • Equipment PID diagram
   • Sampling records
   • Inspection report
   )

Key parameters of cleaning validation

Selection of biological indicators for sterilization validation

• Steam sterilization: Bacillus stearothermophilus (ATCC 7953)
• Dry heat sterilization: Bacillus subtilis (ATCC 9372)
• EO sterilization: Bacillus subtilis (ATCC 9372)

Take the Plastic ampoule filling and sealing machine in Appendix C as an example:

1. Worst condition selection: Drug A with the lowest solubility (0.1g/100mL)
2. Sampling strategy:
   • Rinse water sampling: final discharge port
   • Wipe sampling: 5 key points such as filling needle and sealing mold
3. Acceptance criteria:
   • Microorganisms ≤1CFU/25cm²
   • Endotoxin≤0.25EU/mL

1. Pre-validation preparation:
   • Complete equipment 3Q validation (IQ/OQ/PQ)
   • Establish equipment material certification documents
2. Validation implementation:
   • Use the matrix method to reduce validation batches
   • Establish deviation handling SOP
3. Continuous validation:
   • Evaluate revalidation needs during the annual quality review
   • Perform supplementary validation after change control