GMP Cleanroom Classifications: Understand Class A, B, C And D (2024)

Cleanrooms play a crucial role in the manufacturing of pharmaceutical and medical products by providing controlled environments that minimize the risk of contamination. To ensure the highest standards of cleanliness and safety, regulatory bodies around the world have established guidelines and standards for cleanroom classifications.

In this article, we will delve into the world of GMP cleanroom classifications, exploring the differences between grades, their ISO equivalents, applications, and monitoring requirements.

Introduction to GMP Cleanroom Classifications

The Good Manufacturing Practices (GMP) for cleanrooms were developed to ensure the safety, purity, and quality of pharmaceutical products. GMP standards aim to minimize the risk of contamination from particles, microorganisms, and pyrogens during the preparation and sterilization of medicines and medical devices.

These GxP standards cover various aspects of production, including quality control, packaging, personnel, and the cleanroom facility itself.

Cleanroom Grades and ISO Equivalents

According to Annex 1, GMP cleanrooms are categorized into four grades: Grade A, Grade B, Grade C, and Grade D. Each grade corresponds to specific cleanliness requirements and is associated with ISO classifications. Let’s explore the key characteristics of each grade and their ISO equivalents:

Grade A Cleanroom

Grade A cleanrooms are designated for high-risk operations that require the highest level of environmental control. They are equivalent to ISO Class 5 cleanrooms, both at rest and in operation. Grade A cleanrooms must maintain a low level of airborne particles, with a maximum permitted concentration of 3,520 particles ≥ 0.5 µm per cubic meter.

Grade B Cleanroom

Grade B cleanrooms are used for aseptic preparation, filling, and compounding processes. They are equivalent to ISO Class 5 cleanrooms at rest and ISO Class 7 cleanrooms in operation. The maximum permitted concentration of airborne particles in Grade B cleanrooms is 3,520 particles ≥ 0.5 µm per cubic meter at rest and 352,000 particles ≥ 0.5 µm per cubic meter in operation.

Grade C Cleanroom

Grade C cleanrooms are suitable for less critical stages in the manufacturing process. They are equivalent to ISO Class 7 cleanrooms at rest and ISO Class 8 cleanrooms in operation. The maximum permitted concentration of airborne particles in Grade C cleanrooms is 352,000 particles ≥ 0.5 µm per cubic meter at rest and in operation.

Grade D Cleanroom

Grade D cleanrooms are designated for less critical stages in the manufacturing process. They are equivalent to ISO Class 8 cleanrooms, both at rest and in operation. The maximum permitted concentration of airborne particles in Grade D cleanrooms is 3,520,000 particles ≥ 0.5 µm per cubic meter.

If you want to read more about Annex 1 requirements, read out article SwissMedicines Inspectorate: Interpretation of GMP Annex 1 [2022].

Cleanroom Classification States and Considerations

“At Rest” State: This is when all utilities are installed, including functioning HVAC, and equipment is installed but not operating. No personnel are present in the room.

“In Operation” State: This is when the cleanroom is fully operational, with HVAC functioning, equipment operating in the defined mode, and the maximum number of personnel present for routine work.

“At Rest” State: Establishing Baseline Cleanliness

The “At Rest” state signifies a moment of readiness without active manufacturing operations. In this phase, all utilities, including the vital Heating, Ventilation, and Air Conditioning (HVAC) system, are installed and operational.

Equipment is meticulously arranged but not yet set into motion, and notably, no personnel inhabit the room. The purpose of this state is to establish a baseline for cleanliness, offering insights into the inherent purity of the environment without the influence of human activities or equipment operation.

Total Particle Limits for “At Rest” State:

(a) Classification including 5µm particles may be considered where indicated by the CCS or

historical trends.

“In Operation” State: Real-world Cleanroom Dynamics

Contrasting with the quiescence of the “At Rest” state, the “In Operation” state encapsulates the full spectrum of cleanroom functionality. HVAC is not merely operational but fully engaged, equipment hums in its defined mode, and the cleanroom is bustling with the maximum number of personnel immersed in routine work.

This state serves as a reflection of real-world manufacturing conditions, considering the dynamic factors introduced by human activities and equipment operations.

Total Particle Limits for “In Operation” State:

(a) Classification including 5µm particles may be considered where indicated by the CCS or historical trends.

(b) For grade D, in-operation limits are not predetermined; the manufacturer should establish in-operation limits based on a risk assessment and routine data where applicable.