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Cleanroom Classification in Pharmaceutical Industry – A Complete Guide


Cleanroom Classification in Pharmaceutical Industry – A Complete Guide

Introduction

In the pharmaceutical industry, cleanrooms are the backbone of contamination control. Whether manufacturing oral solid dosage forms (OSD) or sterile injectables, maintaining controlled environmental conditions is critical for ensuring product quality, safety, and regulatory compliance.

To achieve this, cleanrooms are classified based on the concentration of airborne particles and microbial contamination. International standards like ISO 14644, EU GMP Annex 1, and US FDA guidelines provide specific criteria for cleanroom classification.

What is a Cleanroom?

A cleanroom is a controlled environment where parameters such as airborne particle count, temperature, humidity, pressure differentials, and microbial levels are maintained within strict limits.

The HVAC system, HEPA/ULPA filters, and strict gowning procedures ensure the desired cleanliness is achieved and maintained.

Why Cleanroom Classification is Important

  1. Prevents contamination of pharmaceutical products.
  2. Ensures patient safety by maintaining sterile conditions.
  3. Helps in compliance with global regulatory guidelines (FDA, EU, WHO).
  4. Defines the environmental monitoring limits for viable and non-viable particles.
  5. Acts as a foundation for equipment qualification and process validation.

Cleanroom Classification Standards

1. ISO 14644-1 Standard

ISO standards classify cleanrooms based on maximum allowable particles per cubic meter of air.

ISO Class ≥0.5 μm particles (per m³) Typical Application
ISO 5 3,520 Sterile filling, aseptic areas
ISO 7 352,000 Cleanrooms for formulation
ISO 8 3,520,000 Oral solid dosage manufacturing

2. EU GMP Classification

The European Union GMP guideline (Annex 1) classifies cleanrooms into Grades A, B, C, and D.

Grade Cleanroom Type Example Application
Grade A Critical zone (laminar flow) Aseptic filling, open ampoules, vials
Grade B Background for Grade A Buffer for aseptic processing
Grade C Less critical areas Solution preparation, filtration
Grade D General clean area Handling raw materials

3. US FDA Classification

The FDA aligns with both ISO and GMP guidelines, focusing on risk-based cleanroom design and environmental monitoring.

Environmental Parameters in Cleanrooms

During qualification and validation, the following tests are performed:

  1. Airborne Particle Count – Measured using a particle counter as per ISO 14644.
  2. Air Changes per Hour (ACPH) – OSD: 20–25, Sterile: 40–60.
  3. HEPA Filter Integrity Test – PAO/DOP aerosol challenge.
  4. Air Pressure Differentials – Typically 10–15 Pa between rooms.
  5. Temperature & Humidity – Controlled within product-specific ranges.
  6. Airflow Visualization (Smoke Studies) – Confirms laminar/turbulent airflow patterns.
  7. Microbial Monitoring – Settle plates, contact plates, active air sampling.

Cleanroom Qualification Stages

Just like equipment, cleanrooms undergo a stepwise qualification process:

  • Design Qualification (DQ) – Verification of design vs. URS.
  • Installation Qualification (IQ) – Checking HVAC, HEPA, sensors, differential gauges.
  • Operational Qualification (OQ) – Particle count, airflow, recovery, smoke studies.
  • Performance Qualification (PQ) – Real-time monitoring during manufacturing.

Regulatory References

  • ISO 14644-1: Cleanroom Classification by Particle Count
  • EU GMP Annex 1: Manufacture of Sterile Medicinal Products
  • WHO TRS 961 Annex 5: HVAC systems for non-sterile dosage forms
  • US FDA Guidance: Sterile Drug Products Produced by Aseptic Processing (2004)
  • ISPE Baseline Guide: Volume 3 – Sterile Manufacturing Facilities

Conclusion

Cleanroom classification is the foundation of pharmaceutical manufacturing. Whether it’s ISO Class 5 aseptic filling areas or ISO Class 8 OSD rooms, maintaining controlled environments is essential to patient safety, product quality, and GMP compliance.

A validated cleanroom ensures regulatory approval, market credibility, and most importantly, trust in life-saving medicines.


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