Requirements of fermentation system for sterile air

The fermentation system has very strict requirements for sterile air. It is necessary to ensure that the compressed air does not contain microorganisms, particles and other pollutants to ensure the stability of the fermentation process and product safety. The following is a step-by-step description of the key requirements and corresponding measures:

1. Microbiological control

• standard:
  • total number of colonies (CFU/m³): Usually ≤ 1 CFU/m³ (such as pharmaceutical production), food grade may be relaxed to ≤ 10 CFU/m³.
  • Target microorganism: Bacteria, molds, yeasts and viruses (e. g. bacteriophages) need to be excluded.
• Measures:
  • efficient filtration: Adopt sterile filter of 0.2 μm grade(such as PTFE membrane), or dual filtration system (pre-filtration + main filtration).
  • Sterilization Validation: through medium challenge test(e. g. Brevundimonas diminuta) Verify filtration efficiency.
  • Regular monitoring use the contact dish method or settling bacteria to detect airborne microbial content.

2. Particulate matter control

• standard:
  • cleanliness grade: To be reached ISO Class 8(corresponding to GMP grade d), I .e. particles ≥ 0.5 μm ≤ 3520 pc/m.
• Measures:
  • multistage filtration: Air compressor outlet configuration pre-filter (5-10 μm)+ precision filter (1 μm)+ sterile filter (0.2 μm).
  • Piping Design: Avoid dead ends, use electro-polished stainless steel pipe reduce particulate matter shedding.

3. Oil and moisture control

• standard:
  • oil residue: ≤ 0.01 mg/m (not detectable in some scenarios).
  • Relative humidity: usually controlled 40%-60% to prevent the breeding of microorganisms in condensed water.
• Measures:
  • oil-free air compressor: Oil-free lubrication or water lubrication is preferred.
  • oil-water separation: Add after air compressor three-stage oil-water separator(mechanical + freezing + activated carbon adsorption).
  • Drying system: Configuration freeze dryer or adsorption dryer(Dew point ≤ -40 ℃).

4. Pressure and flow stability

• standard:
  • pressure: Maintaining the inside of the fermentation tank positive pressure (e. g. 10-50 Pa) prevent external pollution.
  • Flow: Need to match the fermentation process requirements (e. g. aeration volume, stirring rate).
• Measures:
  • buffer tank: Set sterile air storage tank to balance pressure fluctuations.
  • frequency conversion control: Adjust the output of the air compressor through the inverter to ensure stable air supply.

5. Verification and monitoring

• periodic verification:
  • filter Integrity Test: through bubble point test or diffusion flow test confirm that there is no leakage.
  • Periodic replacement: Replace the filter after its life expires (e. g. every 1-2 years).
• online monitoring:
  • dew point sensor: Real-time monitoring of drying effect.
  • Microbial sampling port: The reserved sampling valve is convenient for daily inspection.

6. Other special requirements

• gas composition: Certain strains need to be controlled O₂/CO₂ ratio(such as micro aerobic fermentation), need to configure the gas mixing device.
• Sterilization method: High-risk scenarios can be used. Steam sterilization filtration system(SIP) or gamma ray pre-sterilization filter.

Application Scenario Differences

• biopharmaceuticals: Requires compliance FDA/EMA GMP Standard, emphasis on sterility assurance level (SAL≤ 10 ∩).
• food fermentation: Focused prevent contamination of bacteria, but a lower microbiological limit (e. g., ≤ 100 CFU/m³) is allowed.

These comprehensive measures ensure that the fermentation system receives high quality sterile air that meets the process requirements, avoiding batch failures or safety risks due to contamination.