API Manufacturing: SOP for Stage-Wise Approval of API Manufacturing – V 2.0

Standard Operating Procedure for Stage-Wise Approval of API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/112/2025
Supersedes	SOP/API/112/2022
Page No.	Page 1 of 10
Issue Date	13/04/2025
Effective Date	15/04/2025
Review Date	13/04/2026

1. Purpose

To define the procedure for obtaining stage-wise approvals during the manufacturing of Active Pharmaceutical Ingredients (APIs), ensuring product quality, process consistency, and regulatory compliance at each critical process step.

2. Scope

This SOP applies to all manufacturing batches of APIs produced at the facility and covers approval checkpoints including raw material charging, reaction monitoring, filtration, drying, milling, blending, and final product release stages.

3. Responsibilities

Production Chemist: Notify QA at each critical manufacturing stage, provide necessary records, and await approval before proceeding.
QA Officer: Review IPC results, perform visual inspections, verify logbook entries, and grant written stage-wise clearance.
QC Analyst: Perform and release IPC test results required for each stage approval.

4. Accountability

The Production Head is accountable for implementing stage-wise controls. The QA Head is responsible for verifying process compliance before approving any manufacturing progression.

5. Procedure

5.1 Identified Manufacturing Stages for Approval

Pre-Reaction: Raw material verification and charging
Reaction Completion: pH, temperature, TLC results
Post-Reaction Work-up: Phase separation confirmation
Filtration: Filtrate clarity and wet cake inspection
Drying: Moisture content (LOD)
Milling and Sieving: Particle size distribution check
Final Blending: Uniformity and identification

5.2 Stage-Wise Approval Process

At each critical stage, Production shall inform QA in writing using the Stage Clearance Request Form (Annexure-1).
QA shall:
- Verify compliance with BMR entries
- Review IPC results from QC
- Check equipment cleanliness and line clearance
- Confirm environmental conditions (if applicable)
Once verified, QA shall record the decision in the Stage Approval Log (Annexure-2) and sign off the BMR page.
Only after written clearance, the next step in manufacturing shall be initiated.

5.3 Documentation

Each stage approval must include:
- Stage description
- Date and Time
- Batch No.
- Verification criteria
- Signature of QA reviewer
In case of hold or rejection at any stage, deviation must be recorded, and batch must not proceed until resolution.

5.4 Re-Approval (If Required)

If a process deviation or batch hold is resolved:
- QA shall reassess the stage parameters, IPC, and process justification.
- Once acceptable, re-approval will be documented with revised date and remarks.

6. Abbreviations

API: Active Pharmaceutical Ingredient
SOP: Standard Operating Procedure
QA: Quality Assurance
QC: Quality Control
BMR: Batch Manufacturing Record
IPC: In-Process Control

7. Documents

Stage Clearance Request Form (Annexure-1)
Stage Approval Logbook (Annexure-2)
Batch Manufacturing Record (BMR)

8. References

ICH Q7 – GMP for Active Pharmaceutical Ingredients
WHO TRS 986 – GMP Guidelines
21 CFR Part 211 – US FDA cGMP Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Stage Clearance Request Form

Stage	Batch No.	Date & Time	Requested By	QA Approval	Remarks
Filtration	API-20250413	13/04/2025 – 11:30	Ravi Kumar		Approved

Annexure-2: Stage Approval Logbook

Date	Stage	Batch No.	QA Review Done	Remarks	Signature
13/04/2025	Drying	API-20250413	Yes	LOD within range

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Release	Compliance Requirement	QA Head
13/04/2025	2.0	Added re-approval clause and annexures for traceability	Audit Recommendation	QA Head