Sterile Injectable Manufacturing: SOP for Reconciliation of Materials Used in Manufacturing – V 2.0

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Sterile Injectable Manufacturing: SOP for Reconciliation of Materials Used in Manufacturing – V 2.0

Standard Operating Procedure for Reconciliation of Materials Used in Manufacturing


Department Sterile Injectable Manufacturing
SOP No. SOP/SIM/039/2025
Supersedes SOP/SIM/039/2022
Page No. Page 1 of 14
Issue Date 18/06/2025
Effective Date 20/06/2025
Review Date 18/06/2026

1. Purpose

To define a standardized procedure for reconciling all materials used in the sterile injectable manufacturing process, including active ingredients, excipients, primary and secondary packaging components, ensuring complete traceability and compliance with cGMP requirements.

2. Scope

This SOP applies to all sterile injectable manufacturing batches processed within the facility, covering raw materials, consumables, primary packaging, and secondary packaging used from dispensing through final batch completion.

3. Responsibilities

  • Manufacturing Executive: Performs reconciliation during and after batch operations and records details in BMR.
  • QA Executive: Verifies and cross-checks reconciliation data and ensures compliance with acceptable variance limits.
  • Warehouse Personnel: Supports material issuance and returns with traceable documentation.
  • Production Supervisor: Ensures physical verification and accuracy of reconciled materials.
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4. Accountability

The Head of Production is accountable for the accuracy, completeness, and verification of all material reconciliation activities in the sterile injectable manufacturing area.

5. Procedure

5.1 Material Reconciliation Types

  1. Raw Material Reconciliation: Reconciliation of active pharmaceutical ingredients (API) and excipients used during formulation.
  2. Packaging Material Reconciliation: Reconciliation of vials, stoppers, seals, labels, cartons, etc.

5.2 During Batch Processing

  1. Verify that the correct quantities of all materials are issued and recorded in the BMR.
  2. Update real-time usage of each component at respective processing stages (e.g., solution preparation, filtration, filling, sealing).
  3. Record any spillage, breakages, line clearance wastage, and overages under appropriate loss categories in the BMR.
  4. Perform intermediate reconciliation at major stages (e.g., post-filling, post-sealing).

5.3 Post-Batch Completion

  1. Calculate the theoretical quantity of materials based on the approved batch size and yield.
  2. Compare with actual used quantities and returned excess materials.
  3. Account for yield losses under defined categories: process loss, handling loss, line loss, etc.
  4. Document in the Material Reconciliation Sheet (Annexure-1).
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5.4 Acceptable Variance Limits

  1. For APIs: ±2%
  2. For Excipients: ±3%
  3. For Packaging Materials: ±5%
  4. Deviation beyond limits must be investigated and deviation form raised (Annexure-2).

5.5 Final Reconciliation Review

  1. QA reviews reconciled data and signs off reconciliation report.
  2. Materials with confirmed reconciliation can be closed in inventory records.
  3. Retain completed reconciliation reports with BMR for a minimum of 5 years.

6. Abbreviations

  • API: Active Pharmaceutical Ingredient
  • BMR: Batch Manufacturing Record
  • QA: Quality Assurance
  • SOP: Standard Operating Procedure

7. Documents

  1. Material Reconciliation Sheet – Annexure-1
  2. Deviation Form – Annexure-2
  3. Batch Yield Summary – Annexure-3

8. References

  • WHO TRS 986 Annex 2 – GMP for Pharmaceutical Products
  • EU GMP Volume 4, Part 1: Chapter 5 – Production
  • 21 CFR Part 211.103 – Calculation of yield
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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: Material Reconciliation Sheet

Material Issued Qty Used Qty Returned Loss Qty Remarks
Sodium Chloride 25 kg 24.2 kg 0.5 kg 0.3 kg Line loss recorded

Annexure-2: Deviation Form

Date Batch No. Material Variance (%) Deviation No. Action Taken
18/06/2025 IV-1025 API 2.8% DEV-093 Investigated and justified

Annexure-3: Batch Yield Summary

Batch No. Theoretical Yield Actual Yield Variance (%) Remarks
IV-1025 5000 vials 4875 vials 2.5% Acceptable range

Revision History

Revision Date Revision No. Details Reason Approved By
10/04/2022 1.0 Initial version New SOP QA Head
18/06/2025 2.0 Updated reconciliation categories and annexures Annual SOP Review QA Head
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