All About Medical Cleanroom

Comprehensive Knowledge of Medical Cleanroom

  Medical cleanroom is a type of dust-free and sterile environment with high cleanliness, widely used in medical, pharmaceutical, biological engineering and other fields. The main function is to control air pollution by controlling air cleanliness, temperature, humidity, differential pressure, noise and other parameters to ensure that specific standards are met in a well-enclosed space. The application of medical cleanroom is not limited to manufacturing environments, but also includes medical sites such as operating rooms, aiming to reduce the risk of infection and improve the quality and safety of healthcare by controlling air quality and environmental parameters. To ensure the cleanliness and safety of medical cleanrooms, codes and standards have been developed in various countries and regions:

 1）Regulatory compliance
Compliance with international standards such as ISO 14644 cleanroom standards and Good Manufacturing Practices (GMP) is non-negotiable. These standards define the classifications of clean rooms and the level of cleanliness required.

2）Medical Cleanroom Classification
The ISO classes for medical cleanrooms are mainly based on the ISO 14644-1 standard, and these classes reflect the degree of control of particle contamination in the cleanroom. The following are common ISO classification and their characteristics for medical cleanroom
ISO1: This is the highest level of cleanliness for special applications that are very sensitive to particle contamination, with a maximum permissible particle concentration of no more than 10 particles at 0.1 micron per cubic meter.
ISO2: For applications that are very sensitive to particle contamination, the maximum permissible particle concentration is no more than 100 particles at 0.1 micron per cubic meter.‌
ISO3: For applications sensitive to particle contamination, the maximum permissible particle concentration is not more than 1,000 particles at 0.1 micron per cubic meter.‌
ISO4: For applications that are more sensitive to particle contamination, the maximum permissible particle concentration is not more than 10,0000 particles at 0.1 micron per cubic meter.‌
ISO5: This is the cleanliness level commonly used for clean operating rooms in the medical industry, with a maximum permissible particle concentration of no more than 100,000 particles at 0.1 micron per cubic meter.
ISO Class 6: For applications with high particle contamination requirements, the maximum permissible particle concentration is not more than 1,000,000 particles at 0.1 micron per cubic meter.‌
ISO7: For applications with average particle contamination requirements, the maximum permissible particle concentration is not more than 10,000,000 particles at 0.1 micron per cubic meter.‌
ISO8: For applications with low particle contamination requirements, the maximum permissible particle concentration is not more than 100,000,000 particles at 0.1 micron per cubic meter.
ISO9: The lowest level of cleanliness and the “dirtiest” level, normally not used in medical cleanrooms.
The ISO 14644-1 standard also specifies other particle populations in cleanroom air that are cumulatively distributed over a range of particle sizes, as shown in the table below:

  These levels are designed to ensure the quality and safety of products in the pharmaceutical process and to reduce the potential for contamination by controlling the number of particles in the air. Pharmaceutical companies need to strictly adhere to these standards when constructing and operating cleanrooms to ensure that the required levels of cleanliness are achieved, thus guaranteeing product quality and hygienic conditions in the production environment.

3）Air quality, temperature and humidity control
The cleanliness level of a medical cleanroom is usually classified according to the number of particles and microorganisms in the air. High Efficiency Particulate Air (HEPA) or Ultra Low Particulate Air (ULPA) filters are critical to maintaining air purity by trapping particles.
In order to meet the process requirements of pharmaceutical production, the temperature and humidity of the clean room should be able to meet the requirements and remain stable.

4）Material suitability
Surfaces within the clean room must be impervious and unobstructed to prevent contamination. Its construction materials mainly include wall, floor and ceiling materials, as well as some special finishing materials. Specifically:
·Walls and materials: Walls and ceilings should be made of smooth, seamless materials to facilitate cleaning and disinfection. Commonly used materials include sandwich panels and aluminum composite panels.
·Door and window design: Doors and windows should be made of airtight materials to reduce the entry of outside air and avoid pollution. At the same time, doors and windows should be designed for easy cleaning and maintenance.
·Floor materials: The floor should be made of wear-resistant, non-slip, easy-to-clean materials, such as epoxy resin flooring or PVC flooring. These materials can effectively prevent the accumulation of bacteria and dust, while providing good anti-slip performance.
In summary, the selection of materials for the construction of medical cleanrooms focuses on the corrosion resistance, ease of cleaning, antimicrobial and antistatic properties of the materials. Surfaces must be impermeable and unobstructed to prevent contamination to ensure the cleanliness and safety of the pharmaceutical environment.

5）Workflow design
To ensure the quality and safety of medicines, the layout of the cleanroom should promote the reasonable flow of materials and personnel to minimize the risk of cross-contamination, which mainly includes the following points:
·Access for people and materials should be set up separately, and normal (non-emergency) access to the cleanroom should be through the airlock for people and materials. Airlock entry and exit doors should be interlocked and cannot be opened at the same time. Transparent Windows can be installed at both ends for sight observation. It is considered to use electrical or mechanical interlocks with audible/visual indication.
·Clean area access control：Personnel entering and exiting the clean area shall strictly follow the procedures for cleanroom entry are and shall carry nothing while entering or exiting. Raw materials entering the clean area must be unpacked and then cleaned in the buffer room before entering, or undergo disinfection measures, and then sent to the pass box or buffer room. Personnel are strictly prohibited to go through the pass through or buffer room in and out of the clean area.
· Emergency exits shall be provided with means to indicate their opening.

6）Medical clean room classification
Medical cleanroom is mainly divided into clean operating room, clean nursing ward and  laboratory cleanroom:
2、Clean operating room:
The clean operating room takes indoor microorganisms as the main control goal to prevent patients from receiving infection after surgery and affecting life safety. The operating parameters, classification index and air cleanliness of clean operating room are the necessary guarantee conditions.
①According to the various types of surgery and different degrees of cleanliness, clean operating rooms are mainly divided into the following categories:
►Special clean operating room (Class I)：The cleanliness of the surgical area is ISO5, and the surrounding area is ISO6. Suitable for sterile procedures such as burns, joint conversion, organ transplantation, brain surgery, ophthalmology, plastic surgery and cardiac surgery;
►Standard Clean Operating Room (Class II)：The cleanliness of the surgical area is ISO6, and the surrounding area is ISO7. Suitable for aseptic surgery such as thoracic surgery, plastic surgery, urology, hepatobiliary and pancreatic surgery, orthopedic surgery and egg retrieval;
►General clean operating room (Class III)：The cleanliness of the surgical area is ISO7, and the surrounding area is ISO8. Suitable for general surgery, obstetrics and gynecology, dermatology and abdominal surgery;
►Quasi-clean operating room (Class IV)：The air cleanliness is ISO 8.5, suitable for obstetrics, anorectal surgery and other surgeries.

Notes：
1. The maximum average concentration of bacteria for the plankton method uses the values in parentheses. Bacterial concentrations are the result of direct measurements, not a conversion of the sedimentation and plankton methods.
2.The cleanliness level of the surrounding area of the ophthalmic operating room can be 2 levels lower than that of the surgical area.

②Requirements for differential pressure in each room of a clean operating department:
a.Between interconnected clean rooms of different cleanliness levels, the room of high cleanliness should maintain relative positive pressure to the room of low cleanliness. The minimum static pressure difference should be greater than or equal to 5 Pa and the maximum static pressure difference should be less than 20 Pa. There should be no whistling or influence on the opening of the door due to the pressure difference.
b.Interconnected clean rooms of the same cleanliness level should have appropriate pressure difference and maintain the required airflow direction.
c.Heavily contaminated rooms shall maintain a negative pressure to the connected adjacent rooms with a minimum static pressure difference of greater than or equal to 5 Pa. Operating rooms used for airborne infection control shall be negative pressure operating rooms, which shall maintain a negative pressure differential of slightly less than “0” to the technical mezzanine on their suspended ceilings.
d.The clean area should maintain positive pressure to the non-clean area connected to it, and the minimum static pressure difference should be greater than or equal to 5Pa.  

③Principles of clean operating room layout：
The floor plan of the clean surgical department must be divided into clean and non-clean areas. A buffer room or pass box must be provided for connection between clean and non-clean areas.
Operating rooms in clean areas should be relatively centralized. Class I and II clean operating rooms should be in the area with the least amount of interference.
Both negative pressure and infected operating rooms should have a preparation room as a buffer room at the entrance and exit. Negative pressure operating rooms should have separate entrances and exits.
Showers and toilets in the changing area are relatively enclosed and should not be located at the rear of the changing room.
When the elevator for human and material use is located in the clean area, and the elevator shaft is connected to the non-clean area, a buffer room must be set up at the back of the elevator.
Air shower room should not be provided in walkways.
Separate storage areas for non-clean and clean areas in the change room are desirable; the area where the clean cart is located shall be part of the clean zone and shall serve as a buffer room.
The buffer room should have an air cleanliness level and be of the same level on the high-level side, up to level 6. The direction of airflow with neighboring rooms should be designed. Buffer room size should not be less than 3 m² and can be used for other purposes at the same time.
A separate hand brushing room should be established for every 2 to 4 clean operating rooms.There should be no door to the hand brushing room; when the hand brushing pool is located in a clean corridor, it should not interfere with traffic and sanitation.

④Clean operating room airflow organization:
Class I ~III clean operating room should have centralized non-inductive air supply device arranged above the operating table to make the certain area including the operating table in the formation of uniform and clean laminar airflow. The air supply area of the air supply unit shall not be less than the values listed in the table below. When the ophthalmic operating room exceeds 30 square meters and the net area of other operating rooms exceeds 50 square meters, and the above air supply area needs to be increased, the proportion of the increase in the air outlet area shall not exceed the proportion of the increase in the net area of the operating room.

  When the centralized air supply surface of the clean operating room needs to be separated, the airflow should be lapped at a height of about 2m above the floor. When the width of the blind zone of air supply after separation is 0.1m~0.25m, the net height of the room is not less than 2.8m~3.2m accordingly.
In class Ⅱ, Ⅲ operating room, air supply surface below the 0.1m of centralized air supply device should have uniform air distribution and even air velocity, preferably between 0.1 m / s ~ 0.4m / s, there shall be no speed of the blind zone. 
Class IV operating rooms could have air supply vents scattered across the ceiling.
Clean operating rooms should adopt indoor return air, which can be returned in the adjacent room attached to it, but should not be organized through the corridor.
Clean operating rooms should use the lower return air from the double side walls parallel to the long side of the operating table; In addition to the front outdoor room, the adjacent room attached to and connected to the clean operating room could only use the return air from the operating room and there is no grade requirement; Rooms with frequent personnel activities and the demand of clean air supply should adopt bottom-return airflow pattern. When the distance between the side walls is greater than or equal to 3m, bottom-return airflow pattern on both sides can be adopted, but not in the four corners. Rooms that are frequently unoccupied and need clean air supply and clean area corridors or other clean channel can have top-return air pattern.
The height of the upper edge of the lower return air opening should not exceed 0.5m above the ground, and the lower edge of the opening should not be less than 0.1m above the ground. Class Ⅰ clean operating room on both sides of the air outlet should be arranged continuously, other levels of operating room on both sides of the return air outlet, each side should not be less than 2, and should be uniformly arranged.
The clean operating room should be equipped with an exhaust port on top, the location of which should be at the top of the patient's head side. The suction velocity of the air vent should not be greater than 2m/s.
Except centralized purification and air-conditioning, in Class Ⅰ ~ Ⅲ clean operating room and negative pressure operating room, extra air purifiers are not needed. Air purifiers with high or higher efficiency filters can be added to other clean rooms.

1. Several kinds of clean nursing wards in hospitals:
Clean nursing units are categorized into isolation and intensive care units. Isolation wards are categorized into P1, P2, P3, and P4 based on biological risk.
Ward P1 is basically the same as the general ward, with no special prohibitions against outsiders entering or leaving;
Ward P2 is a little stricter than ward P1 and is generally off limits to outsiders;
Ward P3 has a buffer room isolated from the outside with negative pressure inside the room;
The P4 ward is isolated from the outside world by a quarantine area, with a constant indoor negative pressure of 30 Pa, and healthcare workers wear protective clothing to prevent infection.
Intensive care units include ICU (intensive care Unit), CCU (coronary care unit), NICU (neonatal intensive care unit) and leukemia room. Leukemia room should have room temperature 24 ℃, wind speed 0.15 ~ 0.3m / s, relative humidity of 60% or less, ISO5 clean class. At the same time, the incoming clean air should firstly reach the head of the patient, so that the mouth and nose respiratory area in the side of the air supply. It is better to use horizontal flow in this regard.
Burns ward is recommended to use vertical laminar flow as bacterial concentration measurement proves that vertical laminar flow has better performance in this case. Burns ward should have laminar flow speed of 0.2m/s and a cleanliness level of ISO class 6.  

2. Laboratory Cleanroom :
  Laboratory Cleanroom are categorized into general laboratories cleanroom and biosafety laboratory. Experiments conducted in a general clean laboratory are not infectious, but require an environment that does not adversely affect the experiment itself. Therefore, there are no protective facilities in the laboratory, but the cleanliness must meet the requirements of the experiment. Biosafety laboratories are biological experiments with certain protective facilities that allow for secondary containment. Biosafety laboratory is required for all scientific experiments in the fields of microbiology, biomedicine, functional experiments and genetic recombination. The core of a biosafety laboratory is safety, which is categorized as P1, P2, P3 and P4 based on the degree of biological risk.
  P1 labs are suitable for very familiar sources of disease that do not regularly cause disease in healthy adults and pose little danger to laboratory personnel and environmental fagots. The door should be closed during the experiment and the operation should be carried out as in an ordinary microbiology experiment;
  P2 labs are suitable for sources of disease with a moderate potential risk to people and the environment.Access to experimental areas is restricted and experiments where aerosols may occur should be conducted in a Class II biological safety cabinet with an autoclave available;
  P3 laboratories are used in clinical, diagnostic, teaching, or manufacturing facilities where work is performed on endogenous and exogenous sources of pathogens that can cause serious and potentially fatal illnesses if exposed and inhaled. The laboratory is equipped with double doors or airlock room and external isolated experimental area, non-staff is prohibited from entering the laboratory, the laboratory full negative pressure, the use of Class II biological safety cabinet for experiments, to high-efficiency filters indoor air filtration and then discharged to the outdoors;
  P4 laboratories are more demanding than P3 laboratories. Some dangerous exogenous pathogens with a high individual risk of laboratory infections and life-threatening diseases due to aerosol transmission should be worked on in P4 laboratories. The laboratory adopts the structure of independent isolation area in the building and external partition, the room maintains negative pressure, uses class III biological safety cabinet to conduct experiments and set up air isolation device, shower room, operating staff should wear protective clothing, non-staff of the Branch is prohibited to enter. The design of biosafety laboratories is centered on dynamic isolation, with ventilation measures as a priority, emphasis on in-situ disinfection, clean and dirty segregation, prevention of accidental spread, and the need for moderate cleanliness.
Medical clean room standard is different from electronic clean room and pharmaceutical clean room, it has a higher degree of cleanliness and sterility requirements, if the clean room device does not meet the cleanliness requirements, resulting in cross-infection within the hospital, will jeopardize the patients and health care workers. In a qualified clean operating room, patient infections can be reduced by a factor of 10 or more, allowing for the use of fewer or no antibiotics that can harm the patient's immune system. Therefore, being both dust-free and sterile is an important feature of medical cleanrooms.

7）Medical clean room applications
  Medical cleanrooms can effectively prevent contamination by external microorganisms and ensure that the quality of products meets the standards. Its application areas mainly include pharmaceutical production, production of vaccines and other biological products, cell culture, genetic engineering and biological experiments.
With the continuous progress of science and technology, the application fields of pharmaceutical cleanrooms are still expanding. The improvement of environmental control capabilities and the demand for high-quality production environment, so that the clean room in the future social and economic development will play a more important role.