Standard Operating Procedure for Jet Milling Operation in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/067/2025
Supersedes	SOP/API/067/2022
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 standard procedure for jet milling operations in the API manufacturing area to ensure consistent particle size reduction, safety, and regulatory compliance.

2. Scope

This SOP is applicable to all jet milling equipment used for micronization or particle size reduction of APIs in the production area. It includes equipment setup, operation, cleaning, and documentation.

3. Responsibilities

• Production Operator: Operate the jet mill as per defined parameters and record observations.
• Production Supervisor: Verify setup and final yield, and review documentation.
• QA Department: Review batch records and ensure compliance.
• Engineering Department: Maintain and calibrate jet mill system and accessories.

4. Accountability

The Production Head is accountable for executing jet milling as per protocol. QA Head is responsible for batch review and final clearance.

5. Procedure

5.1 Pre-Operation Checklist

1. Verify the jet mill equipment is cleaned and labeled as “Cleaned”.
2. Ensure compressed air supply is functional and meets quality parameters.
3. Check calibration status of pressure gauges and flow meters.
4. Ensure all components are properly assembled and tight.
5. Review the Batch Manufacturing Record (BMR) for material to be milled and target particle size.

5.2 Loading and System Setup

1. Transfer material into the feeder hopper using a closed loop or glove box system if applicable.
2. Set inlet air pressure (e.g., 5.0–6.5 bar) and classifier speed (e.g., 3000–5000 rpm) as per BMR.
3. Ensure collection container is properly attached and labeled.
4. Record batch details in the “Jet Milling Log” (Annexure-1).

5.3 Jet Milling Operation

1. Start the air compressor, then gradually feed material using screw or vibratory feeder.
2. Monitor:
   • Feed rate
   • Classifier wheel RPM
   • Air pressure
   • Temperature near outlet (if applicable)
3. Check product periodically for flowability and particle size distribution (PSD) as per in-process controls.
4. Continue milling until all material is processed. Document time, pressure, and observations.

5.4 Post-Milling and Unloading

1. Shut off feeder first, followed by air supply and classifier wheel.
2. Collect milled API into a labeled container using clean tools.
3. Record final yield and reconcile with input weight.
4. Submit sample for QC analysis (e.g., PSD, bulk density).

5.5 Cleaning and Maintenance

1. Disassemble and clean all product contact parts as per equipment cleaning SOP.
2. Visually inspect surfaces for any residue or damage.
3. Record cleaning activity in equipment cleaning log.
4. Inform Engineering for preventive maintenance as per schedule.

6. Abbreviations

• SOP: Standard Operating Procedure
• PSD: Particle Size Distribution
• BMR: Batch Manufacturing Record
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. Jet Milling Log (Annexure-1)
2. Equipment Cleaning Log
3. Batch Manufacturing Record

8. References

• ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• US FDA Guidance on Particle Size Analysis
• Internal Equipment Qualification Protocol

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Jet Milling Log

Date	Batch No.	Input Qty (kg)	Output Qty (kg)	Air Pressure (bar)	RPM	Remarks
13/04/2025	API-MILL-20250413	10.0	9.8	6.0	4500	Uniform PSD

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Release	New Equipment Commissioning	QA Head
13/04/2025	2.0	Added Air Quality and Classifier Controls	Process Enhancement	QA Head