SOP Guide for Pharma

Sterile Injectable Manufacturing: SOP for Filling and Sealing of Injectable Products – V 2.0

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Sterile Injectable Manufacturing: SOP for Filling and Sealing of Injectable Products – V 2.0

Standard Operating Procedure for Filling and Sealing of Injectable Products


Department Sterile Injectable Manufacturing
SOP No. SOP/SIM/033/2025
Supersedes SOP/SIM/033/2022
Page No. Page 1 of 15
Issue Date 18/06/2025
Effective Date 20/06/2025
Review Date 18/06/2026

1. Purpose

To define a standardized procedure for the aseptic filling and sealing of injectable pharmaceutical products to ensure product sterility, container integrity, and compliance with cGMP, WHO, and ICH guidelines.

2. Scope

This SOP applies to the filling and sealing of sterile injectable products (liquid and lyophilized) into glass vials, ampoules, and prefilled syringes at [Insert Facility Name].

3. Responsibilities

  • Machine Operator: Perform equipment setup, operation, and initial checks.
  • Line Supervisor: Ensure compliance, supervise operations, document activities.
  • QA Officer: Perform in-process checks and line clearance.
  • Engineering: Support troubleshooting and maintenance of filling/sealing machines.

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4. Accountability

Production Head is accountable for implementation and adherence to this SOP.

5. Procedure

5.1 Pre-Filling Checks

  1. Verify line clearance as per BMR and previous product status tags are removed.
  2. Ensure HEPA filters, LAF units, and environmental conditions meet required standards.
  3. Confirm sterilization status of components, filters, and containers.
  4. Ensure availability of required labels, BMRs, and logbooks.

5.2 Filling Process

  1. Assemble filling machine parts in LAF area using sterile gloves and gowns.
  2. Attach sterilized solution transfer lines and connect to bulk holding tank.
  3. Prime the filling system using sterile product to remove air bubbles.
  4. Set the fill volume, accuracy tolerance, and run calibration check.
  5. Start filling process after QA approval. Monitor the filling speed, volume accuracy, and reject rate continuously.

5.3 In-Process Controls During Filling

  1. Conduct weight variation checks at intervals of 30 minutes (Annexure-1).
  2. Inspect containers for particulate matter, filling accuracy, and container integrity.
  3. Document all in-process results in the In-Process Inspection Log (Annexure-2).
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5.4 Sealing Process

  1. For vials, immediately place pre-sterilized rubber stoppers on filled vials under LAF.
  2. Transfer vials to sealing machine to apply aluminum seals or flip-off caps.
  3. For ampoules, use flame sealing to close necks after filling under flame station.
  4. Prefilled syringes are sealed using plungers and tamper-evident caps in aseptic chamber.

5.5 Post-Operation Activities

  1. Label the filled and sealed containers as per the batch label record.
  2. Segregate rejected units and log in the Rejection Log (Annexure-3).
  3. Disassemble and clean the filling machine per SOP for cleaning.
  4. QA to verify and release the line after batch completion.

5.6 Documentation

  1. Ensure all logbooks, annexures, and BMR entries are completed in real-time.
  2. Double-check documentation for volume filled, machine settings, rejects, and observations.

6. Abbreviations

  • SOP: Standard Operating Procedure
  • BMR: Batch Manufacturing Record
  • QA: Quality Assurance
  • LAF: Laminar Air Flow
  • HEPA: High-Efficiency Particulate Air

7. Documents

  1. Weight Variation Log – Annexure-1
  2. In-Process Inspection Log – Annexure-2
  3. Rejection Log – Annexure-3
See also  Sterile Injectable Manufacturing: SOP for Dispensing Materials for Intravenous Injections - V 2.0

8. References

  • WHO GMP for Sterile Pharmaceutical Products
  • EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
  • ICH Q8 (R2) – Pharmaceutical Development

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: Weight Variation Log

Date Time Sample Size Average Weight (mg) Deviation Checked By
18/06/2025 10:30 10 502.3 Within Limit Anjali Mehta

Annexure-2: In-Process Inspection Log

Time Observation Result Action Taken Inspector
11:00 Particulate check Pass None Rohit Pawar

Annexure-3: Rejection Log

Date Batch No. Container Type Reason Qty Disposition
18/06/2025 INJ-112 Vial Underfill 6 Discarded

Revision History

Revision Date Revision No. Details Reason Approved By
01/03/2022 1.0 Initial version New SOP QA Head
18/06/2025 2.0 Updated annexures, added weight variation and rejection log Annual Review QA Head
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