Solid Dosage Cleanroom -- Enabling Efficient, Intelligent and Green Pharmaceutical Production

 In the modern pharmaceutical industry, solid dosage clean room plays a pivotal role. It is the core place to ensure the quality, safety and effectiveness of drugs, safeguarding the health of countless patients.

1. What is a solid dosage cleanroom?
Solid dosage clean room is a specially constructed space for the production of tablets, capsules, granules and other solid dosage. It is fundamentally different from ordinary production environments, through a series of precise purification technology and strict control measures. The indoor dust particles, microorganisms, temperature and humidity, differential pressure and other environmental factors are controlled within the prescribed standards. For example, in accordance with China's Good Manufacturing Practice (GMP) requirements, different class of clean room areas have strict limits on the number of dust particles, generally divided into Class A, B, C, D:
● Class A: It is the highest class of clean area, where the number of dust particles larger than or equal to 0.5 microns per cubic meter of air shall not exceed 3520. This area is often used for critical operations such as sterile drug filling and freeze-drying and other key operation, which requires high sterility requirements for the environment. Laminar airflow technology is required to maintain unidirectional airflow, ensuring continuous purification of air and minimizing the risk of microbial contamination.
● Class B: The cleanliness is slightly inferior to that of Class A, where the number of dust particles larger than or equal to 0.5 micron in each cubic meter of air does not exceed 35,200, typically serving as the background environment for Class A areas, providing assurance for operations that require higher sterility but are not the most critical steps, such as the preparation and filtration of sterile drugs. It is adjacent to Class A area to prevent contamination from entering to Class A areas through reasonable airflow organization and pressure differential control.
● Class C: The number of dust particles larger than or equal to 0.5 microns per cubic meter of air does not exceed 352,000, which is applicable to some routine processes in the production process of solid dosage, such as weighing and mixing of materials, etc. Although the restriction on dust particles is relatively loose, the number of microorganisms should be strictly controlled to ensure that the quality of drugs is not affected.
● Class D: It’s the basic class of clean room, where the number of dust particles greater than or equal to 0.5 micron per cubic meter of air is not more than 3,520,000, mainly used in auxiliary areas of drug production, such as packaging workshop, etc., where the flow of personnel and materials is relatively frequent. But through appropriate purification measures, it can effectively isolate most outdoor contamination, ensuring the basic cleanliness of the pharmaceutical production environment.

2. Key design elements
A. Space layout
  Reasonable space layout is the foundation. It is generally divided into production areas, auxiliary areas, personnel flow channels, and materials channels and so on. Production areas are arranged with equipment in an orderly manner according to the production process to ensure smooth material flow and prevent cross-contamination; Personnel and material flow channels are strictly separated. Normally, personnel enters the clean area from changing room through air shower, while materials enter after being disinfected through dedicated dynamic pass box or other types of material channels to avoid mixing of contaminants carried by personnel and materials.

B. Air filtration system
  This is the "heart" of the clean room. The multi-class filtration system is composed of primary, medium and high efficiency filters. The fresh air is filtered layer by layer and sent into the room to continuously dilute and replace the indoor air.
▶ Air supply requirements: The air supply volume needs be accurately calculated based on the volume of the clean room, the number of personnel, the heat generation of equipment, and the desired cleanliness cleanliness. Typically, Class A clean areas should adopt unidirectional airflow (horizontal/vertical) design, while B to D areas can use non-unidirectional airflow (top supply bottom return/side supply bottom return) design; The average cross-sectional air speed in Class A laminar flow clean areas should be controlled at 0.36~0.54m/s, while B to D non-laminar flow clean areas can design air supply volumes according to the air change rate. The higher the cleanliness class, the more air changes are required. For example, Class B clean areas generally require 40-60 times air changes per hour to ensure rapid air renewal and purification of indoor air. The arrangement of air supply outlets should be evenly distributed to avoid dead zones and ensure that the entire clean area is effectively covered by fresh air. Moreover, the air supply temperature and humidity should be appropriate, meeting the comfort needs of personnel while also contributing to the physical and chemical stability of pharmaceutical production processes.
▶ Differential pressure control: Maintain a stable differential pressure gradient in each area by adjusting the air supply volume, return air volume and exhaust air volume. High-cleanliness areas are kept at positive pressure relative to lower-cleanliness areas to prevent contaminated air from flowing back and affecting drug quality; However, the operation area with large amount of dust production should maintain negative pressure relative to the surrounding clean area to prevent cross contamination. For example, in a tablet pressing workshop, in order to prevent dust dispersion, a negative pressure of 10-15 Pa can be maintained relative to adjacent corridors; And for critical sterile operation areas, such as under Class A laminar airflow booth, positive pressure of no less than 10 Pa should be maintained relative to surrounding Class B areas to ensure environmental purity in key zones. Differential pressure between different class of clean areas, and between clean areas and non-clean areas have to be monitored in real-time and accurately. If any abnormal fluctuations in pressure are detected, immediate alarms should be triggered to identify the cause, which can include issues such as ventilation system failures or poor sealing of doors and windows.
▶ Temperature and humidity control: Temperature and humidity have a significant impact on the drugs quality and production processes. Generally, if there is no special requirement for the production process, the temperature in the clean area of class A/B should be 20~24℃ and the relative humidity should be 45%~60%, while the temperature in Class C/D clean rooms should be 18~26℃ and the relative humidity should be 45%~65%. In the production process of solid preparations such as tablets, capsules, granulation, compression, packaging or filling, etc., the relative humidity has more stringent requirements. If the relative humidity is too high, the hygroscopic effect of the drug will increase significantly, the fluidity of the drug will be reduced, affecting the dose and product quality. In processes sensitive to static electricity, such as powder mixing, excessively low humidity can easily lead to static electricity accumulation, causing dust dispersion or even explosion risks. Therefore, the clean room is equipped with specialized temperature and humidity control equipment, such as air conditioning units, humidifiers, and dehumidifiers, etc., through the sensor real-time monitoring of temperature and humidity data, feedback to the control system, automatic adjustment of the operating state of the equipment in order to maintain a stable environmental temperature and humidity.

3.Wall panels, flooring and ceiling panels
  Selection of non-dust-producing, easy-to-clean, and corrosion-resistant materials. The most commonly used wall panels are sandwich panel with a smooth and flat surface that does not allow dirt to hide in the seams; Flooring usually adopts epoxy self-leveling or rubber PVC flooring, with excellent wear resistance and anti-static properties; Ceiling panels adopt sealed suspended ceilings to prevent dust accumulation and facilitate the installation and maintenance of facilities such as lighting fixtures and ventilation outlets.

4.Process characteristics, purification and dust removal measures in solid dosage workshops
▶ In the production process of solid dosage forms, apart from the strict requirements for temperature and humidity, dust dispersion is most likely to occur in the weighing, mixing, sieving, granulation, tablet pressing, capsule filling, powder filling, and other procedures, especially through the mixing of drugs or cross-contamination caused by the purification of air conditioning system. The problem is even more serious for the dust with strength, irritation and allergy. Therefore, dust control and removal have become important issues to be solved in the production of solid dosage.
▶To prevent dust from flying and spreading to pollute the entire workshop environment, it is necessary to first isolate the dust sources according to the characteristics of dust-producing equipment. A buffer room should be set up at the entrance of the isolation area, maintaining the same cleanliness class as the isolation area while keeping its pressure higher than that of the isolation area and the outside workshop, so as to avoid cross contamination due to the dispersion of the dust in the isolation area to the outside workshop. At the same time, a ventilation system should be installed in the isolation area to discharge the generated dust pollution nearby, preventing the dust from entering the purification air conditioning system, which could affect the lifespan of the purification filters and cause drug mixing and cross-contamination.
▶The dust contaminated air in the isolation area can be filtered by the exhaust dust removal system and then discharged outdoors, but the overall environment of the workshop is a clean area, maintaining positive pressure relative to the outdoor area. The exhaust air from the isolation area will be supplemented with air from surrounding workshops, increasing the overall fresh air volume of the workshop, while the heat and humidity load of the air conditioning system increases, significantly raising the energy consumption of the workshop operation. Therefore, from the perspective of energy saving and environmental protection, the exhaust air from the isolation area can also be filtered by dust removal and then returned to the isolation area again, forming a self-circulation. Alternatively, part of the filtered air can be discharged outdoor area to maintain the negative pressure relative to surrounding workshops in the isolation area, while the remaining part is returned to the isolation area to complete the purification air circulation. This ensures that the workshop environment in each area is not affected by dust while allowing the purification air conditioning system to operate efficiently and energy-saving.

3. Application and advantages of modular solid dosage clean room
  In recent years, modular solid dosage clean room has gradually emerged and been widely used in the field of pharmaceutical production.
▶ Rapid Construction and Flexible Layout: Modular clean room adopts prefabricated modules which are standardized in production at the factory and then transported to the site for rapid assembly. Compared with the traditional on-site construction method of clean rooms, the modular cleanroom significantly shortens the construction period and meets the needs of pharmaceutical enterprises for rapid production. Moreover, module units can be flexibly combined and laid out according to different process flows and site spaces of pharmaceutical enterprises, allowing for personalized customization and improving space utilization whether it is a small R&D laboratory or a large production workshop.
▶ Quality Control and High Stability: Due to the centralized production of modules in a factory environment with stable production conditions, the raw materials and manufacturing processes are easy to manage which ensures good quality consistency of the modules. The assembled clean room structure has excellent sealing performance and is not prone to problems such as gap leakage, which can effectively maintain stable environmental parameters within the clean room and minimize the impact of environmental fluctuations on the quality of pharmaceuticals.
▶ Easy to Upgrade and Retrofit: With the development of pharmaceutical technology and changes in production processes, the requirements of pharmaceutical enterprises for clean rooms may change. Modular clean rooms facilitate partial module replacement, upgrades, or functional expansion without the need for large-scale dismantling and reconstruction, reducing downtime and renovation costs, thus providing strong support for the continuous development of pharmaceutical enterprises.
▶ Cost-effectiveness Advantage: On the one hand, the rapid construction of modular clean rooms reduces on-site construction time, lowering labor costs and time costs; On the other hand, its stable quality reduces the post maintenance costs. Overall, it offers significant cost-effectiveness throughout the entire life cycle, making it highly attractive for small and medium-sized pharmaceutical enterprises as well as cost-sensitive projects.

4. Details of intelligent solid dosage cleanroom
  With the rapid development of science and technology, intelligent technology is deeply integrated into the field of solid dosage clean room, opening a new management mode.
▶ Environmental Intelligent Monitoring and Control: Utilizing high-precision sensor networks to conduct 24-hour uninterrupted real-time monitoring of parameters such as dust particle count, microbial content, temperature and humidity, and differential pressure in the clean room. These sensors are not only highly accurate, but also have a self-calibration function to ensure the accuracy of the data. Once there are abnormal fluctuations in the data, the intelligent control system will immediately start to automatically adjust the operating parameters of the air-conditioning unit, humidifier, dehumidifier, supply and exhaust fans and other equipment to restore environmental stability at the fastest speed. For example, when the temperature in a certain area rises above the set point by 26℃, the system will automatically increase the cooling capacity of the air conditioning units while adjusting the supply air volume to ensure that the temperature quickly returns to an appropriate range.
▶ Equipment Intelligent Operation and Maintenance: By installing intelligent sensors on production equipment and air purification equipment, comprehensive monitoring of equipment operation status can be achieved. It allows for real-time tracking of key parameters such as rotational speed, vibration, temperature, and pressure, utilizing big data analysis technology to predict equipment failures in advance. For example, based on historical data models, when the resistance of high-efficiency filters increases abnormally in a short period, the system will issue early warnings, prompting maintenance personnel to replace them in time, avoiding environmental loss of control and production interruptions caused by equipment failures. At the same time, the intelligent system can also automatically generate equipment maintenance schedules, reasonably arranging maintenance cycles according to the actual usage conditions of the equipment, significantly improving equipment operation and maintenance efficiency.
▶ Personnel Intelligent Management: In the process of personnel entering and exiting clean rooms, biometric recognition technologies such as facial recognition and fingerprint recognition are adopted to quickly and accurately identify personnel identities, automatically record entry and exit times, achieving precise control over personnel entry and exit. After entering the clean room, intelligent wristbands or badge devices worn by personnel can monitor their movement trajectories and dwell times in real-time, preventing personnel from mistakenly entering restricted areas or staying too long in sensitive zones. Once an violation is detected, the system will immediately issue an alarm to remind personnel to correct their actions, while recording and archiving the violation information for subsequent traceability and analysis. Additionally, these wearable devices can be integrated with environmental monitoring systems, notifying nearby personnel to evacuate or take appropriate measures when environmental abnormalities occur in a specific area.
▶ Material Intelligent Traceability and Control: Assigning unique electronic tags to every batch of materials entering the clean room from reception storage requisition processing to finished product packaging. The entire process is tracked and recorded using IoT technology. By scanning the electronic tags production managers can query detailed information about the source batch quality inspection reports, processing procedures etc. at any time ensuring the traceability of material quality. During the material flow process the intelligent logistics system automatically plans the delivery routes and times based on production progress and equipment status avoiding material accumulation and cross-contamination improving material delivery efficiency.

5. Strict operation management
▶ Personnel control
  Personnel entering the clean room must undergo systematic training and be familiar with the operating procedures of the clean room. They should wear complete clean room workwear, including a hat, mask, full-body suit, gloves, and shoe covers, to minimize the emission of human skin flakes, hair, microorganisms, etc. Before each entry, strict hand washing and disinfection must be performed, and they should follow the specified routes within the clean room, strictly prohibiting random touching of equipment, walls, and other surfaces.
▶ Equipment maintenance
  Regular maintenance and upkeep of production equipment and air purification equipment are required. For instance, high-efficiency filters should be checked for resistance regularly, and they should be replaced promptly when the resistance reaches a certain value to ensure filtration efficiency; pharmaceutical equipment must undergo cleaning validation to ensure that the surface is free of drug residues and microbial growth, preventing contamination of subsequent batches of drugs.
▶ Environmental monitoring
  Continuous real-time monitoring of parameters such as dust particle counts, microbial limits, temperature and humidity, and pressure differences in clean rooms is required. Once any abnormalities are detected, an immediate investigation and corrective action procedure should be initiated. For example, regular inspections using dust particle counters should be conducted, and if the dust particle count in a specific area exceeds the standard, promptly investigate whether the filters are damaged or if material transfer procedures are being followed correctly, and make timely corrections.

6. Challenges and future development
  With the continuous advancement of pharmaceutical technology, solid dosage clean rooms are also facing new challenges. On one hand, new drug formulations are more sensitive to the environment, requiring continuous improvement in the precision control of clean rooms; on the other hand, reducing energy consumption and improving operational efficiency are also key focuses of the industry. In the future, intelligent technologies will deeply empower clean room management, achieving precise environmental parameter control, equipment failure warning, and personnel behavior analysis through the Internet of Things, big data, and artificial intelligence, creating more efficient, intelligent, and green solid dosage form clean rooms to lay a solid foundation for the thriving global pharmaceutical industry.
In short, the clean room of solid dosage forms, with its precise design and strict management, guards the pure birth of every piece of medicine and every capsule, and writes a solid guarantee for human health and well-being.