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

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

5.2 Stage-Wise Approval Process

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

5.3 Documentation

1. Each stage approval must include:
   • Stage description
   • Date and Time
   • Batch No.
   • Verification criteria
   • Signature of QA reviewer
2. 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)

1. 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

1. Stage Clearance Request Form (Annexure-1)
2. Stage Approval Logbook (Annexure-2)
3. 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