In aseptic pharmaceutical manufacturing, positive and negative pressure isolators serve different purposes based on the type of product and contamination risks. Here’s a clear breakdown of where each is used and why:
✅ Positive Pressure Isolators (PPI)
Purpose:
To protect the product from contamination by maintaining a higher pressure inside the isolator than in the surrounding environment.
Where Used:
- Aseptic filling of sterile, non-hazardous products
- Parenteral formulations, ophthalmics, and biologics that are not cytotoxic or potent
- High-speed fill-finish lines in sterile facilities
How it works:
- Clean, HEPA-filtered air is supplied to the isolator.
- Positive pressure ensures that in case of any leak, air will flow outward, preventing ingress of contaminants.
Example Use Cases:
- Monoclonal antibody vials
- Sterile water for injection (WFI) ampoules
- Vaccine filling (non-live, non-hazardous)
❌ Negative Pressure Isolators (NPI)
Purpose:
To protect the operator and environment from potentially hazardous or toxic substances.
Where Used:
- Filling of cytotoxic, potent, or hazardous drugs
- Oncology products (e.g., chemotherapy agents)
- Hormonal or biologically active compounds with occupational exposure risks
How it works:
- The isolator is kept under negative pressure relative to the room.
- In case of leaks, air flows into the isolator, preventing escape of hazardous material.
Often combined with:
- Double HEPA filtration on exhaust
- Glove integrity testing
- Decontamination systems (H2O2)
Example Use Cases:
- Cytotoxic drug vial filling
- Hormonal injection ampoules
- Antibody-drug conjugates (ADCs)
🔄 Hybrid or Dual-Pressure Systems
Some modern isolators are dual-zone, using:
- Positive pressure in critical fill zones (for product protection)
- Negative pressure around transfer or decontamination chambers (for operator safety)
Summary Table
| Pressure Type | Goal | Used For | Protects |
| Positive | Product protection | Sterile, non-toxic formulations | Product |
| Negative | Operator/environment safety | Toxic/cytotoxic formulations | Operator + Env |