Grade B aseptic environments used in sterile injectable manufacturing operations including filling, stoppering, lyophilization, and related processes.

3. Responsibilities

• Production Personnel: Follow aseptic practices and gowning procedures strictly.
• QA Officer: Perform routine particulate monitoring and review results.
• Engineering Team: Maintain HVAC systems and ensure HEPA filter integrity.
• Microbiology Analyst: Conduct environmental particulate monitoring using calibrated particle counters.

4. Accountability

The Head of Manufacturing is accountable for the implementation and enforcement of contamination control strategies in aseptic areas, and ensuring all deviations are addressed and investigated.

5. Procedure

5.1 Cleanroom Gowning Practices

1. Personnel shall be trained and qualified in aseptic gowning before entry into cleanrooms.
2. Gowning shall be done in a stepwise fashion through classified change rooms (Grade D to Grade B).
3. Cleanroom garments must be sterile, non-linting, and free from damage. Gloves must be powder-free and sterile.
4. Any breach in gown integrity must be reported immediately and rectified.

5.2 Housekeeping and Cleaning Controls

1. Use only approved lint-free wipes and mops in the aseptic area.
2. Follow predefined cleaning schedules for walls, floors, equipment surfaces, and ceilings.
3. Clean Grade A surfaces at the beginning, during, and after operations using approved disinfectants.
4. Replace mop heads and wipes frequently to prevent shedding or particle dispersal.

5.3 Environmental Monitoring for Non-Viable Particles

1. Use calibrated laser particle counters to monitor 0.5 µm and 5.0 µm particle sizes.
2. Perform monitoring at:
   • Start and end of each filling session
   • During critical operations
   • After any maintenance activity
3. Record and evaluate results using alert and action limits defined per ISO 14644-1 standard.
4. Document monitoring data in Annexure-1.

5.4 Equipment and Material Transfer

1. Ensure materials and components entering aseptic zones are sterile or sterilized by validated methods.
2. Use airlocks with interlocking doors and material pass-boxes for transfer.
3. Perform particle decontamination by wiping with sterile 70% IPA prior to entry.

5.5 Maintenance of HVAC and HEPA Filters

1. Maintain air change rates as per classified area requirements (e.g., >240 ACH in Grade A).
2. Ensure unidirectional airflow is maintained over critical zones at ≥0.45 m/s ± 20%.
3. HEPA filters must be integrity tested semi-annually using PAO or DOP test methods.
4. Record and report test results in Annexure-2.

5.6 Identification and Investigation of Particle Sources

1. If particle counts exceed action limits:
   • Stop aseptic operations and notify QA immediately.
   • Initiate deviation report and conduct root cause analysis.
   • Possible sources include: garment damage, glove shedding, equipment malfunction, or filter leak.
2. Document findings in Annexure-3.

5.7 Training and Qualification

1. All personnel shall undergo initial and periodic refresher training in:
   • Aseptic behavior and movements
   • Gowning procedures
   • Contamination risk reduction
2. Maintain training records in Annexure-4.

6. Abbreviations

• SOP: Standard Operating Procedure
• HEPA: High Efficiency Particulate Air
• ACH: Air Changes per Hour
• IPA: Isopropyl Alcohol
• QA: Quality Assurance
• HVAC: Heating, Ventilation and Air Conditioning

7. Documents

1. Non-Viable Particle Monitoring Log – Annexure-1
2. HEPA Filter Integrity Test Report – Annexure-2
3. Particle Source Investigation Log – Annexure-3
4. Aseptic Area Training Log – Annexure-4

8. References

• EU GMP Annex 1: Manufacture of Sterile Medicinal Products
• ISO 14644-1: Classification of air cleanliness
• WHO TRS 961 Annex 6

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: Non-Viable Particle Monitoring Log

Date	Area	0.5µm Count	5.0µm Count	Operator
24/06/2025	Filling Line A	215	1	Rajesh Kumar

Annexure-2: HEPA Filter Integrity Test Report

Filter ID	Location	Test Date	Result	Tested By
HEPA-07	Grade A Zone	22/06/2025	Pass	Sunita Reddy

Annexure-3: Particle Source Investigation Log

Date	Deviation	Probable Source	Corrective Action	Approved By
20/06/2025	Particle >5µm Detected	Garment Fiber	Re-trained operator and replaced gown	QA Manager

Annexure-4: Aseptic Area Training Log

Employee Name	Training Date	Trainer	Topics Covered	Status
Ajay Verma	10/06/2025	QA Officer	Aseptic Practices	Completed

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial issue	New SOP	QA Head
24/06/2025	2.0	Updated monitoring points and HEPA test section	Annual review	QA Head