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Clean Room Design and Classification

Clean room design and classification in the pharmaceutical and medical device industry involve creating controlled environments with specific cleanliness levels to prevent contamination and maintain product quality. Here are the key aspects of clean room design and classification:

Clean Room Design:

  1. Environmental Controls: Clean rooms require precise control over temperature, humidity, air pressure differentials, and air filtration to minimize particulate and microbial contamination. HVAC systems play a crucial role in maintaining the desired environmental conditions.
  2. Airflow and Filtration: Clean room design includes strategically designed airflow patterns to control the movement of particles and ensure proper air exchange. High-efficiency particulate air (HEPA) filters and/or ultra-low particulate air (ULPA) filters are used to remove particles of specified sizes.
  3. Materials and Surfaces: Clean room construction materials and surfaces should be smooth, non-shedding, and easy to clean to minimize the generation and accumulation of contaminants. Flooring, walls, ceilings, and fixtures are typically made of materials that meet cleanliness and compatibility requirements.
  4. Pressure Differentials: Differential air pressure is used to prevent the entry of contaminants from adjacent areas. Clean rooms may have positive pressure (higher pressure inside) or negative pressure (lower pressure inside) depending on the application and required contamination control.

Clean Room Classification:

Clean rooms are classified based on the maximum allowable number of particles per cubic meter of air. The classification is determined by the International Organization for Standardization (ISO) standard 14644-1. The classification system is represented by an ISO class number, with ISO class 5 being the cleanest and ISO class 9 being the least clean.

EU GMP Annex 1: The EU GMP (Good Manufacturing Practice) Annex 1 is a guideline that provides specific requirements for the manufacture of sterile medicinal products. It includes requirements for clean room design and operation. The EU GMP Annex 1 refers to the ISO classification system as a means of assessing the cleanliness level of clean rooms.

Alignment of Clean Room Classifications: The EU GMP Annex 1 and ISO classifications are closely aligned, but there may be slight differences in terminology and specific requirements. The EU GMP Annex 1 generally adopts the ISO classification system for clean rooms used in the pharmaceutical industry.

The EU GMP Annex 1 and ISO classifications are harmonized to ensure consistency and regulatory compliance. The EU GMP Annex 1 provides additional requirements and guidance specific to the manufacture of sterile medicinal products, while the ISO classifications serve as a broader international standard applicable to various industries.

It's important to note that the EU member states may have additional regulations and guidelines specific to clean room classifications, which may be based on both the EU GMP Annex 1 and ISO standards. Therefore, it is essential for pharmaceutical companies operating in the EU to comply with both the EU GMP requirements and relevant ISO standards for clean room design and classification.

The classification of a clean room is determined by the particle size range being considered, such as 0.5 microns or larger, 0.3 microns or larger, or 5 microns or larger. The number of particles in each size range is measured using particle counting equipment.

EU Classification vs ISO Equivalent1 2
EU Classification ISO Equivalent (Static) ISO Equivalent (Dynamic)
Class A EU Annex 1 - 3,520 ISO 4.8 - 3,520
Class B ISO 5 - 3,520 ISO 7 - 352,000
Class C ISO 7 - 352,000 ISO 8 - 3,520,000
Class D ISO 8 - 3,520,000 Not Defined
1 ISO 14644-1:2015 – Table 1 – ISO Classes of air Cleanliness by particle concentration.
2 EudraLex Vol.4 – Annex 1. - Manufacture of Sterile Medicinal Product

It is important to note that the design and classification of clean rooms should align with regulatory requirements, industry guidelines, and specific product requirements. Compliance with good manufacturing practices (GMP) and regular monitoring and maintenance of clean room conditions are essential to ensure product quality and patient safety.