microorganisms (critical in sterile facilities)

Validation Lifecycle: DQ → IQ → OQ → PQ

Design Qualification (DQ)

• Define intended use: Direct contact, indirect, or utility
• Specify filtration: 0.01 µm point-of-use filters, sterilizing-grade membrane if required
• Materials of construction: Stainless steel vs polymer piping
• Distribution loop with sloping lines and drain points
• Monitoring points for dew point, pressure, and flow

Installation Qualification (IQ)

• Confirm pipe layout per design drawings
• Ensure proper installation of regulators, dryers, and filters
• Document filter integrity test certificates
• Verify installation of sample ports at defined locations
• Check for proper labeling and flow direction indicators

Operational Qualification (OQ)

Test system functionality under standard conditions:

• Flow and pressure testing at usage points
• Verify dew point monitoring (should be ≤ -40°C for sterile use)
• Filter efficiency and bypass valves functional check
• Alarms and interlocks for pressure drops or dew point excursions

Performance Qualification (PQ)

PQ focuses on the air quality at the point of use. The following tests should be performed as per ISO 8573 recommendations:

1. Particulate Count Test

• Use laser particle counters connected via isokinetic probes
• Test for 0.5 µm and 5.0 µm particles
• ISO 8573-1 Class 1: < 20,000 particles/m³ @ 0.5 µm

2. Oil Mist and Vapor Test

• Test using gravimetric oil vapor collectors
• Limit: Class 1 = ≤ 0.01 mg/m³
• Consider both compressor oil and maintenance residue

3. Microbial (Viable) Testing

• Impaction method using air samplers onto TSA or SDA plates
• 1000 liters sampled per point
• Incubate at 30–35°C for 3–5 days
• Limit for sterile manufacturing: ≤1 CFU/m³

4. Dew Point Measurement

• Measure at lowest usage point using hygrometer
• Acceptable dew point: -40°C or lower for sterile areas

Sample Test Matrix

Test	Frequency	Acceptance Criteria
Particulate Count	Annual	Class 1 (ISO 8573)
Oil Vapor Test	Annual	≤ 0.01 mg/m³
Microbial Count	Quarterly	≤ 1 CFU/m³
Dew Point	Monthly	≤ -40°C

Documentation and Protocols

• Compressed Air Validation Protocol (includes sampling plan)
• IQ/OQ/PQ reports with raw data and test results
• Filter installation and replacement records
• Microbial test data, CFU count sheets, plate images (optional)
• CAPA and deviation reports

Common Deviation Examples

• Oil mist exceeding 0.01 mg/m³ → Check compressor seals
• Microbial contamination detected → Replace point-of-use filters
• Dew point excursion → Verify dryer efficiency and perform maintenance

Requalification Strategy

• Annual requalification recommended
• Earlier if system modifications, contamination, or critical deviations occur
• Filters replaced after defined usage cycle (e.g., 6 months or 1000 hours)

Conclusion

Compressed air and gas validation is a GMP-critical activity, particularly in sterile manufacturing areas. Contaminants such as particulates, microbes, oil vapors, and moisture must be controlled through engineering design, filtration, monitoring, and periodic validation. Adhering to ISO 8573 standards and regulatory expectations ensures safe use of compressed gases throughout pharmaceutical processes.

For ready-to-use compressed air validation protocols, sampling SOPs, and filter testing templates, visit PharmaSOP.in. To integrate utility validation into your sitewide VMP, explore our complete solutions at PharmaValidation.in.

Additional Resources

• ISO 8573-1:2010 Standard
• FDA Guidance on Process Validation
• EMA GMP Annex 1
• ICH Q9 – Quality Risk Management