Biotechnology Cleanroom

 Biotechnology Cleanroom

I. What is a Biotechnology Cleanroom?

  A biotechnology cleanroom is a cleanroom where airborne microorganisms are the primary control object. The standards for this type of cleanroom mostly adopt the cleanroom classification method and add requirements for microbial control. These laboratories must ensure personal safety, environmental safety, waste safety and sample safety, be able to operate safely and for a long time, and provide a comfortable and good working environment for laboratory staff. The establishment of a biotechnology cleanroom requires consideration of how to prevent the spread of dangerous microorganisms to the outside world, comprehensively block the contact path between dangerous microorganisms and the external environment, and avoid microorganisms samples from being contaminated by the outside world, which may affect the accuracy of experimental results.

II. Biotech Cleanroom Applications

Biotechnology cleanrooms are mainly used by research institutions for microbiology, biomedicine, biochemistry, animal experiments, genetic recombination and biological products, so they are also called clean laboratories or biosafety laboratories. Specific application industries include pharmaceutical industry, hospital operating rooms, blood wards, central supply rooms, reproductive centers, food and beverage production, animal laboratories, physical and chemical testing laboratories, cosmetics, blood stations and other fields, and the control standards for microorganisms and other life particles are more stringent.

III. ISO Classification of Biotechnology Cleanrooms

The ISO classification of biotechnology cleanrooms is mainly based on the ISO14644-1 standard and is divided into different cleanliness levels, among which ISO5 is the highest cleanliness. According to the ISO14644-1 standard, the cleanliness level of a cleanroom is divided according to the number of 0.1μm particles per cubic meter of air. Specifically for biotechnology clean rooms, ISO5 has the highest cleanliness level, which means that there are only a maximum of a hundred particles per cubic feet of air in the cleanroom. Some special products, such as bioengineering, can be produced in this environment. As the cleanliness level decreases, the cleanliness level of ISO6 is class 1,000, ISO7 is class 10,000, ISO8 is class 100,000, and other levels can be found in the following table:

IV. Requirements for biotechnology cleanroom design

(1)Layout design‌：the layout design of the clean laboratory is the basis of the entire laboratory decoration. It is necessary to reasonably separate different functional areas to reduce the possibility of cross contamination. It usually includes sample preparation area, experimental operation area, instrument and equipment area, sample storage area, etc.

(2)Personal purification route and material purification route‌：People and materials are one of the main sources of contamination in clean laboratories, so it is very important to design personal purification routes and material purification routes. People need to go through purification channels for personal purification to reduce the introduction of external pollutants; at the same time, material imports and exports need to be set up, and material purification processes need to be established to ensure that experimental materials have been fully purified before entering the laboratory.

(3)Selection of HVAC room location‌：The HVAC room plays a key role in the microbiological clean laboratory. Its location and functional layout are crucial to the laboratory's operating efficiency and safety. The HVACroom should be as close to the experimental area as possible to reduce the length and loss of pipelines. At the same time, it should be far away from areas where pollution sources may occur to ensure the stability and reliability of the equipment.

(4)Pipeline Organization:Pipeline organization affects the normal operation of laboratory equipment and the smooth progress of the experimental process. Pipelines need to be divided and graded according to their functions so as to ensure the normal operation of laboratory equipment and the smooth progress of the experimental process.

(5)Cleanroom indicators‌：The main function of the cleanroom is to control the cleanliness, temperature and humidity of the atmosphere that the product is exposed to (temperature is usually 18~26℃, relative humidity is 30~60%), so that the product can be produced and manufactured in a good environment. The cleanroom design needs to meet specific cleanliness standards, such as controlling the number of dust particles with a particle size of less than 0.3 microns to less than 3,500 per cubic meter.

(6)Clean laboratory air flow pattern design‌：The airflow pattern should meet the requirements of the air cleanliness level. When the air cleanliness level requirement is ISO 6-8, the airflow method of upper supply and lower side return should be adopted. The opening and closing of the supply, return and exhaust systems should be interlocked. The interlocking procedure of the positive pressure cleanroom is to start the supply fan first, then the return fan and the exhaust fan.

(7)Biosafety laboratories should implement both primary and secondary barriers. The primary barrier is mainly reflected in the layout and maintenance structure of the microbiological experimental area, and the secondary barrier is mainly reflected in the air conditioning purification system. In terms of layout, the flow of people and goods are separated to prevent cross infection between people and objects.

V. How to choose the right biotech cleanroom for your needs?

Choosing a biotechnology cleanroom that fits your needs requires consideration of multiple factors, including application requirements, product characteristics, process requirements, budget constraints, etc.
Here are some key considerations and steps:
(1)Identify application requirements: First, we need to clarify the main purpose of the clean room. Is it used for animal experiments, gene recombination, or other industries that require a highly clean environment? Different products and different experimental objects have different requirements for cleanliness.

（2)Understand the cleanroom level standards: Common biotechnology cleanroom levels include ISO6, ISO 7, ISO 8, etc. These grades are based on different requirements for the concentration of airborne particles in the air. Understanding the specific requirements and standards of each grade, including parameters such as air cleanliness, temperature, humidity, pressure, etc., will help to choose the appropriate grade.

(3) Ealuation of Experiment Requirements: Analyze the key steps in the experimental process to determine which steps have strict requirements for cleanliness. Consider the continuity and batch size of production to select the cleanroom level suitable for the experimental environment.

(4) Consider budget and costs:The construction and operating costs of cleanrooms of different grades will vary. According to budget constraints, choose a cleanroom level that meets both production needs and cost efficiency.

(5) Consider future expansion and upgrades: If you expect to expand production or improve product quality in the future, choose a cleanroom classification with a certain degree of scalability. Consider the upgradeability of the equipment and systems inside the cleanroom to meet the needs of future technological development.

(6) Contact Airkey: When choosing the cleanroom level for biotechnology, you can consult Airkey, the professional cleanroom design, construction and maintenance experts. We can provide professional advice and solutions based on specific needs and conditions.

(7) Site visits and comparisons: Before choosing a suitable biotechnology cleanroom, you can visit some built cleanrooms to understand the actual effects and operating conditions of cleanrooms of different grades. By comparing the advantages and disadvantages of different cleanrooms, you can choose the cleanroom level that best suits your needs.

VI. Why Biotechnology Facilities Need Cleanroom?

The main reasons why biotechnology facilities need clean rooms include ensuring production quality and safety, meeting special operating requirements, complying with regulations and standards, and promoting R&D innovation.

(1) First, cleanrooms strictly control air quality, temperature, humidity and microbial contamination by using high-efficiency filters and air flow control technology to ensure the manufacturing quality and safety of bio-pharmaceutical products. This environmental control helps prevent impurities and contaminants from entering the production process, minimizes the impact on product quality, and ensures that the produced biological products meet the predetermined standards and requirements.

(2) Secondly, cleanrooms provide key operating locations for special operations such as bio-pharmaceuticals, for example, virus culture, cell culture, bacterial fermentation, preparation filling, and drug preparation. These operations need to be carried out under strict clean conditions to reduce the risk of microbial contamination and the possibility of cross-contamination and product deterioration, which is crucial for the high purity, activity, and safety requirements of biological products.

(3) They provide controlled air filtration to create a safe environment, reducing the possibility of product contamination or large particles disrupting critical process manufacturing. They create classified environments to protect processes from harmful air contaminants, maximizing performance by protecting sensitive equipment from harsh environments.

VII. Biotechnology Cleanroom Operating Procedures and Training

The operating procedures and training of biotechnology clean rooms mainly involve the following aspects:

(1) Reasonable partition and cleaning: Cleanrooms should be divided into clean areas, semi-contaminated areas and contaminated areas to ensure smooth experimental processes and reduce the risk of cross-contamination. Ensure good ventilation and appropriate lighting, and regularly disinfect and sterilize the laboratory to ensure a sterile experimental environment.

(2) Equipment and reagent management: Select high-quality equipment that meets the experimental requirements, and thoroughly clean and disinfect the equipment before and after the experiment to avoid cross contamination. Reagents should be stored in categories and clearly labeled. Check the expiration date and properties before use to ensure experimental safety. Record the experimental process, data analysis and results in detail to ensure that the experiment is traceable and repeatable.

(3) Waste Disposal: Classify and collect waste generated by the experiment, and treat the waste in accordance with environmental protection requirements, such as high temperature and high pressure sterilization, chemical treatment, etc. Strengthen the environmental awareness of experimenters and reduce the impact of experiments on the environment.

(4) Safety Basics: By taking necessary protective measures, we can prevent or reduce the harm or potential risks caused by biological factors to humans, animals, plants and the environment. We can ensure the safety of laboratory staff, the public and the environment; ensure the smooth progress and application of biotechnology research; and maintain national biosafety and ecological security.

(5) Emergency treatment: Develop emergency response measures to deal with possible biosafety incidents. This includes establishing an emergency response mechanism, providing necessary personal protective equipment, conducting regular emergency drills, etc.

(6) Through the above procedures and training, the operational safety, environmental safety and personnel safety of the biotechnology cleanroom can be ensured, thereby ensuring the smooth progress of biotechnology research and the application of its results.

VIII. Cleaning and maintenance of biotechnology cleanrooms

In order to maintain the cleanliness of the air in the biotechnology cleanroom, relevant maintenance regulations must be strictly implemented to prevent the generation, retention and reproduction of dust particles and microorganisms in the clean room and ensure the safety of equipment and personnel.

A.Worker Management in Biotechnology Cleanrooms
1. Hands are the medium of cross contamination. Workers must wash their hands before entering the cleanroom and avoid touching high-purity items and high-purity packaging materials with their hands. Pharmaceutical production workers also need to be disinfected.
2. The following persons are not allowed to enter the cleanroom: patients with colds, coughs, eczema and other diseases; those who do not wash off their cosmetics and nail polish as required and do not wear clean work clothes; workers should wash their hair, change clothes and cut their nails frequently.
3. When working in a cleanroom, operators should move gently, strictly follow the operating procedures, avoid making large movements that may generate dust, avoid dragging their feet when walking, and avoid making unnecessary movements; they are not allowed to go to the toilet while wearing clean work clothes.
4. In a cleanroom, you must wear gloves as required, do not expose your wrists, and change gloves frequently.
5. Personnel entering the cleanroom must receive relevant training and education: master the characteristics, structure, general knowledge of clean technology of the cleanroom, personnel purification procedures and material purification route requirements, the use and cleaning requirements of clean work clothes, cleaning, washing and disinfection of the cleanroom, and the safety facilities and safety management regulations of the cleanroom.
6. Clean work clothes should be made of clothes with less dust production and anti-static electricity. Generally, the split type is used in clean rooms of class 1 to 100,000, and the one-piece type is used in class 100 to 1,000. Disposable cleanroom shoe covers are preferred, and cleanroom shoes are required to be washable.
7. Clean work clothes should be managed by a dedicated person, checked and cleaned regularly. Generally, they should be cleaned once a week, and usually after 50 to 100 cleanings, they should be checked to determine whether they are replaced.

B. Cleaning and sterilization of cleanrooms
(1)Cleaning of the cleanroom must generally be carried out after the production process is completed; if it is necessary to clean before production, the process production must not begin until the purification air conditioning system has been turned on and running for a period of time that meets the cleanliness requirements. 
(2)To prevent cross contamination, the cleaning facilities of cleanrooms should be dedicated according to product characteristics, process requirements, and cleanliness levels. Cleaning tools generally use centralized fixed and portable mobile vacuum cleaning equipment. If the above conditions are not met, you can also use fiber-free materials such as mercerized towels and nylon cloths for wiping, generally once or several times a day. The workbench and tools are generally cleaned once a day. The purification air conditioning system should be cleaned 1 to 2 times a year, and it should be entrusted to a special cleaning staff.
(3)In addition, the entire cleanroom being disinfected and sterilized should be in a circulating state through the return air duct, and the air should be sterilized for 1-1.5 hours every day; if the clean room walls, floors, equipment and other surfaces need to be disinfected and sterilized, it will take about 2 hours.
(4)When using a high-efficiency vacuum cleaner for cleaning in a cleanroom, the dust concentration at the vacuum cleaner exhaust port must be checked regularly.

C.Main equipment maintenance
1.High efficiency filter replacement conditions：
a.The air flow rate is reduced to the minimum, and even after replacing the primary and medium efficiency air filters, the air flow rate still cannot be increased.
b.The resistance of the high-efficiency filter is twice the initial resistance.
c.The high efficiency filter has an irreparable leak.
d.It is recommended to replace it once a year. 

2. Medium efficiency filter inspection and cleaning:
Each section is equipped with a bag-type medium efficiency filter to further filter and remove dust from fresh air and return air. It is recommended to inspect and replace it every three months, or increase or decrease the inspection or replacement frequency as appropriate. Be careful when replacing it to avoid puncturing the filter bag or bumping or deforming the frame to avoid affecting the filtering effect.

3.Primary efficiency filter inspection and cleaning:
Each air conditioning unit is equipped with a primary efficiency filter near the entrance of its fresh air duct, which is mainly used to prevent dust, mosquitoes, etc. brought by fresh air from entering the air conditioning system. Therefore, it needs to be inspected and replaced. It is recommended to inspect and replace it every 45 days, or increase or decrease the inspection and replacement frequency as appropriate.

4.Each air-conditioning unit has regulating valves installed on its supply and return air ducts. To ensure their safety and reliability, they should be inspected in accordance with relevant national regulations.

5.In order to ensure the accuracy of the temperature in the factory, the operator should regularly check the purification air conditioning unit every day to determine whether the unit is operating normally and whether there are any abnormal sounds.

IX. Differences between Biotechnology Cleanrooms and Industrial Cleanrooms