Sterile Injectable Manufacturing: SOP for Sterilization of Manufacturing Equipment – V 2.0

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Sterile Injectable Manufacturing: SOP for Sterilization of Manufacturing Equipment – V 2.0

Standard Operating Procedure for Sterilization of Manufacturing Equipment


Department Sterile Injectable Manufacturing
SOP No. SOP/SIM/032/2025
Supersedes SOP/SIM/032/2022
Page No. Page 1 of 14
Issue Date 18/06/2025
Effective Date 20/06/2025
Review Date 18/06/2026

1. Purpose

To lay down a standardized procedure for sterilization of manufacturing equipment used in sterile injectable product manufacturing, ensuring compliance with cGMP, WHO, and ICH guidelines and prevention of microbial contamination.

2. Scope

This SOP applies to all major and minor equipment including

vessels, pipelines, transfer containers, and filter assemblies used in sterile injectable manufacturing at [Insert Facility Name].

3. Responsibilities

  • Manufacturing Operator: Perform sterilization procedures as per SOP and batch record instructions.
  • Production Supervisor: Ensure execution, documentation, and verification of sterilization activities.
  • QA Executive: Verify equipment readiness and perform pre- and post-sterilization checks.

4. Accountability

The Head – Production is accountable for effective implementation and compliance with this SOP.

5. Procedure

5.1 Preparation for Sterilization

  1. Ensure equipment is cleaned as per relevant SOPs and verified by QA.
  2. Affix “To Be Sterilized” status label on the equipment.
  3. Check and record equipment cleaning status in Annexure-1: Equipment Cleaning Checklist.
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5.2 Assembly of Components

  1. Assemble the equipment under LAF using sterile gloves and garments.
  2. Ensure connections are leak-tight and clamped appropriately.
  3. Seal open ends of transfer pipes and accessories using sterile end caps.

5.3 Sterilization Methods

Select the sterilization method based on equipment type:

  • Autoclaving: For stainless steel vessels, filters, tubing, etc.
  • Dry Heat Sterilization: For glass components and metal tools not compatible with moist heat.
  • SIP (Steam In Place): For fixed transfer lines, manufacturing tanks, and bioreactors.

5.4 Autoclaving Procedure

  1. Load equipment into the autoclave ensuring separation for steam circulation.
  2. Use a validated sterilization cycle (e.g., 121°C for 30 minutes at 15 psi).
  3. Place chemical/biological indicators inside to verify sterilization.
  4. Record cycle details in Annexure-2: Autoclave Run Log.

5.5 Steam In Place (SIP)

  1. Connect steam inlet and outlet lines securely to the equipment.
  2. Start SIP cycle and monitor critical parameters like temperature, pressure, and time.
  3. Maintain temperature above 121°C for a minimum of 30 minutes.
  4. Record SIP data in Annexure-3: SIP Monitoring Log.
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5.6 Dry Heat Sterilization

  1. Place glassware or metal parts inside a depyrogenation tunnel or dry heat oven.
  2. Operate at validated conditions (e.g., 250°C for 30 minutes).
  3. Use thermocouples to confirm uniform temperature distribution.

5.7 Post-Sterilization Activities

  1. Affix “Sterilized” status label with sterilization date and expiry date (if applicable).
  2. Transfer sterilized items to sterile area using validated pass-throughs or trolleys.
  3. Maintain equipment in covered, sterile conditions until use.

5.8 Filter Integrity Testing

  1. Conduct pre- and post-use filter integrity tests for sterilized filter assemblies.
  2. Document results in Annexure-4: Filter Integrity Test Log.

5.9 Documentation

  1. Ensure all logs and annexures are completely filled, reviewed, and archived.
  2. QA to perform a line clearance check before equipment use.

6. Abbreviations

  • SOP: Standard Operating Procedure
  • SIP: Steam In Place
  • QA: Quality Assurance
  • cGMP: current Good Manufacturing Practice

7. Documents

  1. Equipment Cleaning Checklist – Annexure-1
  2. Autoclave Run Log – Annexure-2
  3. SIP Monitoring Log – Annexure-3
  4. Filter Integrity Test Log – Annexure-4

8. References

  • WHO TRS 961 – Annex 6: Good Manufacturing Practices for Sterile Products
  • ICH Q9 – Quality Risk Management
  • ISO 17665 – Sterilization of Healthcare Products
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9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation Manufacturing Executive QA Executive Head QA
Department Production Quality Assurance Quality Assurance

11. Annexures

Annexure-1: Equipment Cleaning Checklist

Equipment Name ID Cleaning Done On Done By Checked By
Preparation Vessel VSL-101 17/06/2025 Vikas Sharma QA – Ritu Malhotra

Annexure-2: Autoclave Run Log

Date Batch No. Cycle Time Temperature Pressure Status
18/06/2025 ST-0425 30 min 121°C 15 psi Pass

Annexure-3: SIP Monitoring Log

Equipment Start Time End Time Max Temp Hold Time Status
Tank-201 09:00 10:00 124°C 32 min Pass

Annexure-4: Filter Integrity Test Log

Date Filter ID Pre-Test Result Post-Test Result Status
18/06/2025 F-8971 Pass Pass Compliant

Revision History

Revision Date Revision No. Details Reason Approved By
01/04/2022 1.0 Initial SOP creation New process documentation QA Head
18/06/2025 2.0 Included SIP and updated annexures Annual Review QA Head
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