Manufacturing Validation: SOP for Validation of Sterilization Cycle in Manufacturing – V 2.0

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Manufacturing Validation: SOP for Validation of Sterilization Cycle in Manufacturing – V 2.0

Standard Operating Procedure for Validation of Sterilization Cycle in Manufacturing


Department Manufacturing Validation
SOP No. SOP/MV/121/2025
Supersedes SOP/MV/121/2022
Page No. Page 1 of 14
Issue Date 24/06/2025
Effective Date 26/06/2025
Review Date 24/06/2026

1. Purpose

To establish a standard methodology for the validation of sterilization cycles used in the manufacturing of sterile injectable products. This includes moist heat, dry heat, and gaseous sterilization procedures. The validation confirms cycle efficacy, equipment consistency, and compliance with cGMP,

WHO, and ICH guidelines.

2. Scope

This SOP applies to autoclaves, dry heat sterilizers, ethylene oxide (EtO) chambers, and vapor hydrogen peroxide (VHP) units used for sterilizing product contact equipment, garments, and components in the sterile manufacturing facility.

3. Responsibilities

  • Validation Team: Designs protocol, executes cycles, and evaluates results.
  • Engineering: Supports instrumentation calibration and cycle setup.
  • Microbiology: Prepares biological indicators (BIs) and performs microbial analysis.
  • Quality Assurance: Reviews and approves protocols, reports, and deviations.
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4. Accountability

The Head of Manufacturing Validation is accountable for executing and maintaining sterilization cycle validation. QA Head is accountable for compliance and final approval of validation documentation.

5. Procedure

5.1 Preparation for Validation

  1. Identify equipment requiring validation (e.g., Autoclave-01, Dry Heat Sterilizer-02).
  2. Ensure all relevant instruments (thermocouples, pressure gauges, timers) are calibrated and documented.
  3. Draft validation protocol including:
    • Objective
    • Scope
    • Acceptance Criteria
    • Cycle Parameters
    • Equipment Details
    • BI Placement Map
  4. Use protocol template (Annexure-1) for consistency.

5.2 Installation Qualification (IQ)

  1. Verify installation of all components (e.g., steam inlet, drain, chamber integrity, gasket fitting).
  2. Check availability of operation and maintenance manuals.

5.3 Operational Qualification (OQ)

  1. Run three empty cycles under defined load configurations.
  2. Place thermocouples at multiple locations (corners, center, near the drain) to monitor uniformity.
  3. Check for alarm systems, safety interlocks, and chart recorders.

5.4 Performance Qualification (PQ)

  1. Conduct three consecutive successful loaded cycles using dummy loads or actual items.
  2. Incorporate biological indicators (Geobacillus stearothermophilus for moist heat) at cold spots.
  3. Ensure sterility assurance level (SAL) of 10⁻⁶.
  4. Confirm thermal mapping (F₀ ≥ 12 minutes) using thermocouples.
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5.5 Biological Indicator (BI) Analysis

  1. Retrieve BI post-cycle and incubate at 55-60°C for 7 days.
  2. Include positive and negative controls.
  3. Log results in BI Test Log Sheet (Annexure-2).

5.6 Acceptance Criteria

  • All BIs show no growth post incubation.
  • All thermocouples record within ±2°C of setpoint.
  • Chart recorder and SCADA show consistent data.

5.7 Documentation

  1. Record all findings in Validation Report Template (Annexure-3).
  2. Summarize deviations, corrective actions, and revalidation, if applicable.

5.8 Revalidation

  1. Conduct revalidation every 12 months or in the event of:
    • Major maintenance/repairs
    • Cycle parameter changes
    • Component replacement (e.g., heating coil, vacuum pump)

6. Abbreviations

  • SOP: Standard Operating Procedure
  • IQ: Installation Qualification
  • OQ: Operational Qualification
  • PQ: Performance Qualification
  • BI: Biological Indicator
  • SAL: Sterility Assurance Level
  • SCADA: Supervisory Control and Data Acquisition
  • F₀: Equivalent Lethal Time at 121°C

7. Documents

  1. Validation Protocol Template – Annexure-1
  2. BI Test Log Sheet – Annexure-2
  3. Validation Report Template – Annexure-3
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8. References

  • ICH Q9 – Quality Risk Management
  • USP <1211> – Sterilization and Sterility Assurance
  • WHO TRS 961 Annex 6 – GMP for Sterile Products

9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation Validation Engineer QA Executive Head QA
Department Validation Quality Assurance Quality Assurance

11. Annexures

Annexure-1: Validation Protocol Template

Protocol ID Equipment Cycle Type Prepared By Date
VP-STER-2025-05 Autoclave-01 Moist Heat Sunita Reddy 01/06/2025

Annexure-2: BI Test Log Sheet

Date Cycle ID BI Lot Location Growth Tested By
05/06/2025 AC-MH-092 BI2025G Drain Point No Growth Rajesh Kumar

Annexure-3: Validation Report Template

Report ID Equipment Date of Completion Summary Approved By
VR-2025-013 Dry Heat Sterilizer 15/06/2025 All criteria met Dr. Meera Joshi

Revision History

Revision Date Revision No. Details Reason Approved By
10/05/2022 1.0 Initial Release New SOP QA Head
24/06/2025 2.0 Updated acceptance criteria and BI testing Annual Review QA Head
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