1. Introduction
Pharmaceutical cleanrooms are critical environments where temperature, humidity, air quality, and particulate control are tightly regulated to prevent contamination during healthcare treatment, drug manufacturing and research. Thermal comfort is essential in these spaces for operators working in stringent conditions, often under sterile suits and personal protective equipment (PPE). This article explores the role of thermal comfort indices, such as Predicted Mean Vote (PMV) and Predicted Percentage Dissatisfied (PPD), and discusses the key standards—ISO classifications, ASHRAE guidelines, and Biosafety Levels (BSLs)—that govern pharmaceutical cleanroom design and operation.
Figure 1. Computational domain of a representative cleanroom. The domain was meshed with 17.2 million poly-hexcore elements.
Figure 2. Velocity magnitude in the pharmacy cleanroom.
Inlet mass flow rate at each swirl diffuser is at 0.0677 kg s-1, corresponds to ACH of 10 h-1. At the outlet faces, zero gauge pressure is imposed.
Figure 3. Velocity vector in the pharmacy cleanroom.
2. Thermal Comfort Indices in Cleanrooms
Thermal comfort in cleanrooms must be carefully managed due to the unique environment and attire of personnel. PMV (Predicted Mean Vote) and PPD (Predicted Percentage Dissatisfied) are two critical indices used to assess thermal comfort.
2.1. PMV Index
PMV quantifies the thermal sensation of occupants on a scale from -3 (cold) to +3 (hot). The ideal comfort range lies between -0.5 and +0.5. In cleanrooms, PMV calculations must account for factors such as air temperature, air velocity, mean radiant temperature, humidity, metabolic rate, and clothing insulation. Operators in sterile suits with high clothing insulation often experience discomfort due to heat build-up. Therefore, HVAC systems in cleanrooms must be optimized to maintain a neutral PMV to ensure operator comfort and productivity.
2.2. PPD Index
The PPD index predicts the percentage of people likely to feel dissatisfied with the thermal conditions in the environment. PPD values are directly related to PMV; a PMV of 0 corresponds to a PPD of 5%, which is considered optimal. For cleanrooms, the aim is to maintain a PPD below 10%, ensuring that at least 90% of the workforce experiences adequate thermal comfort despite the demands of sterile clothing and PPE.
Figure 4. Temperature map inside the cleanroom. Surface heat flux on upper body of human at 83.33 W m-2, yielding a total of 80 W per person.
Figure 5. Particle track of contaminants. The particle emitter operating at 0.30 m s-1, emitting particles of size 0.3-5 μm.
3. Cleanroom Classification and Standards
Maintaining cleanliness, air quality, and sterility in pharmaceutical cleanrooms is achieved through adherence to stringent standards that govern air change rates, particle limits, and containment protocols.
3.1. ISO Cleanroom Standards
The ISO 14644-1 standard defines cleanroom classifications based on airborne particulate levels. Cleanrooms are categorized into classes according to the concentration of particles ≥0.5 microns per cubic meter.
ISO Class 1: Less than 10 particles.
ISO Class 5: Common in pharmaceutical manufacturing, allowing up to 3,520 particles.
ISO Class 8: Typically used for less critical processes, allowing up to 3,520,000 particles.
In pharmaceutical environments, ISO Class 5 is often the standard for sterile product manufacturing, where stringent particle control is critical to avoid contamination. The design and operation of the HVAC system must ensure the correct number of air changes per hour (ACH) to maintain this classification.
3.2. ASHRAE Standards
The ASHRAE 55 standard governs thermal environmental conditions for human occupancy, providing guidelines for temperature, humidity, and air velocity to achieve thermal comfort. For cleanrooms, the HVAC system must be designed to balance particulate control with thermal comfort, often challenging due to the high air exchange rates and cooling loads associated with particle filtration and the protective clothing worn by personnel.
ASHRAE 62.1 outlines ventilation standards that ensure indoor air quality in cleanroom environments. It specifies the minimum ventilation rates needed to remove contaminants, which is critical in preventing contamination of pharmaceutical products. The system must integrate both fresh and recirculated air to meet the required ventilation effectiveness while maintaining thermal comfort.
3.3. Biosafety Levels (BSL)
Pharmaceutical cleanrooms that handle biological agents must adhere to Biosafety Levels (BSLs), particularly when working with hazardous materials such as viral vectors or genetically modified organisms. Each level outlines specific requirements for containment, ventilation, and sterilization.
BSL-1: Suitable for low-risk biological agents (non-pathogenic organisms like E. coli K-12 strain).
BSL-2: Involves moderate-risk agents (e.g., Staphylococcus aureus, Salmonella, hepatitis, HIV), requiring biosafety cabinets for procedures likely to produce aerosols.
BSL-3: Used for work with airborne pathogens that may cause serious disease (e.g., Mycobacterium tuberculosis, SARS-CoV-2, Yellow Fever Virus), requiring more stringent containment, negative pressure rooms, and HEPA filtration.
BSL-4: Highest level, designed for work with highly dangerous pathogens like Ebola virus, Marburg virus, where personnel wear fully encapsulated suits and air is HEPA-filtered twice.
For cleanrooms adhering to BSL-3, thermal comfort can become challenging due to the need for negative pressure to prevent pathogen escape and the use of full-body protective equipment. PMV and PPD calculations for these environments must factor in higher metabolic rates due to the physical effort of working in pressurized suits, as well as the impact of localized cooling strategies.
4. HVAC System Design for Pharmaceutical Cleanrooms
Incorporating thermal comfort while meeting strict cleanliness and biosafety standards requires a carefully designed HVAC system. Key design considerations include-
Airflow patterns: Unidirectional or laminar airflow is used in cleanrooms to minimize particle movement, reducing contamination risk. This airflow pattern can affect thermal comfort, so proper air velocity control is critical.
Temperature and humidity Control: Maintaining a narrow range of temperature (typically 18-22°C) and relative humidity (30-60%) is essential for both product stability and operator comfort.
Filtration: HEPA (High-Efficiency Particulate Air) filters, capable of trapping 99.97% of particles ≥0.3 microns, are essential for achieving the particle concentrations required by ISO standards.
Energy recovery: Cleanroom HVAC systems are energy-intensive due to high air change rates and filtration requirements. Heat recovery systems can be used to reduce energy consumption while maintaining precise temperature control.
5. Conclusion
Thermal comfort indices like PMV and PPD are integral to ensuring that pharmaceutical cleanrooms not only meet stringent air cleanliness and safety requirements but also provide a comfortable working environment for operators. Compliance with standards such as ISO 14644, ASHRAE guidelines, and BSL classifications ensures that pharmaceutical products are manufactured under optimal conditions, minimizing contamination risks while balancing thermal comfort challenges. Careful HVAC system design is key to achieving these goals, integrating advanced air filtration, airflow control, and energy management strategies tailored to the specific needs of pharmaceutical cleanroom environments.
