Cleanrooms in Plasma & Pharma Manufacturing
 
1.   Cleanroom Grades (A, B, C, D)
 
🔹 Grade A – Critical Zone

The highest level of cleanliness, where the product is directly exposed during aseptic operations.
Examples:
 

• Aseptic filling of vials and syringes
   

• Ampoule sealing
   

• Sterile connections
   

• Open sterile equipment handling
  
   

Requirements:
 

• Unidirectional airflow (laminar flow) with HEPA filters
   

• Air velocity: ~0.36–0.54 m/s to sweep away particles
   

• Pressure differentials to protect from less clean areas
   

 
Particulate Limits (per m³):
 

• At rest: 3,520 particles ≥0.5µm; 0 particles ≥5µm
   

• In operation: 3,520 particles ≥0.5µm; 0 particles ≥5µm
   

 
Simple Term: 👉 The “surgical zone” of pharmaceutical manufacturing.
 
🔹 Grade B – Background for Grade A

The supporting clean area surrounding Grade A zones.
Examples:
 

• Background for filling machines
   

• Personnel gowning area before entering Grade A
   

 
Requirements:
 

• Works in tandem with Grade A
   

• HEPA-filtered air supply
   

• Maintained pressure differential vs. Grade C/D
   

 
Particulate Limits (per m³):
 

• At rest: 3,520 particles ≥0.5µm; 29 particles ≥5µm
   

• In operation: 352,000 particles ≥0.5µm; 2,900 particles ≥5µm
   

 
Simple Term: 👉 The “buffer zone” around aseptic filling.
 
🔹 Grade C – Clean Area

Used for less critical stages of sterile product manufacturing.
Examples:
 

• Preparation of solutions before sterile filtration
   

• Staging of equipment and materials
   

 
Requirements:
 

• HEPA-filtered air
   

• Not aseptic-critical, but controlled environment
   

 
Particulate Limits (per m³):
 

• At rest: 352,000 particles ≥0.5µm; 2,900 particles ≥5µm
   

• In operation: 3,520,000 particles ≥0.5µm; 29,000 particles ≥5µm
   

 
Simple Term: 👉 The “preparation area” before entry into aseptic zones.
 
🔹 Grade D – Controlled Area

The lowest cleanroom grade, used for non-critical stages.
Examples:
 

• Raw material preparation
   

• Bulk powder weighing (before sterilization)
   

• Washing/cleaning of equipment (before sterilization)
   

 
Requirements:
 

• General clean air supply (not as strict as A–C)
   

 
Particulate Limits (per m³):
 

• At rest: 3,520,000 particles ≥0.5µm; 29,000 particles ≥5µm
   

• In operation: Not defined (depends on process risk assessment)
   

 
Simple Term: 👉 A “controlled but not sterile” support area.
 
2. Types of Cleanrooms
 

• Conventional Cleanroom → Entire room is controlled with HVAC + HEPA.
   

• Laminar Airflow (LAF) Cleanroom → Controlled airflow in a single direction (used in Grade A).
   

• Modular Cleanroom → Flexible, pre-fabricated panels for fast setup & expansion.
   

• Hard wall Cleanroom → Permanent, rigid wall panels (common in pharma).
   

• Soft wall Cleanroom → Flexible curtain walls, used for temporary or less critical operations.
   

• Isolators / RABS → Closed barrier systems providing Grade A protection with minimal human intervention.
   

 
3. Key Equipment in Pharma/Plasma Cleanrooms
Air & Environmental Control:
 

• AHUs (Air Handling Units) – maintain temperature, humidity, pressure differentials.
   

• HEPA / ULPA Filters – for particle control.
   

• LAF Units (Laminar Airflow workbenches) – aseptic manipulations.
   

• Pass Boxes / Pass-Through Chambers – for material transfer.
   

• Airlocks (Personnel & Material) – contamination control.
   

 
Processing Equipment:
 

• Fractionation tanks – for plasma separation.
   

• Chromatography systems – for protein purification.
   

• Filtration units (sterile / ultrafiltration) – virus removal, purification.
   

• Aseptic filling & stoppering machines – vials, ampoules, syringes.
   

• Lyophilizes (Freeze-dryers) – for plasma proteins & injectables.
   

 
Utility & Support Systems:
 

• WFI (Water for Injection) Systems – critical clean utility.
   

• CIP/SIP Systems (Clean/Steam-in-place) – automated cleaning & sterilization.
   

• Compressed Air, Nitrogen, CO₂ Systems – process gases.
   

• Cold Rooms & Freezers – plasma storage.
   

 
Monitoring & Safety:
 

• Particle counters – for environmental monitoring.
   

• Bio-decontamination units (H₂O₂ fumigation) – sterilization.
   

• Differential pressure gauges – air pressure monitoring between zones.
   

 
4. Cleanroom Personnel & Flow Control
 

• Personnel Flow: Gowning sequence → Grade D → Grade C → Grade B → Grade A.
   

• Material Flow: Raw → staged in Grade D/C → sterilized transfer → final aseptic use in Grade A.
   

• Barriers: Airlocks, pass boxes, pressure cascades.