Microorganisms are easily spread everywhere. Asepsis is the method of practice to reduce or eliminate contaminants from the working area and to make the area sterile and clean. The contaminants are like bacteria, viruses, fungi, and other parasites. The area free from contamination is known as an aseptic area.
Table of Contents
Atmosphere
Atmospheric gases namely oxygen and carbon dioxide are the main sources for microbial growth. Oxygen has a more significant effect on microbial growth. Dust particles in the outside air are the main carriers for the soil organisms like Clostridium, yeast, molds, etc. Indoor air also contains bacteria like streptococcus, staphylococcus species on cloths, or human skins. These microorganisms are also present in droplets expelled out from the mouth and respiratory tract of humans while talking, sneezing, and coughing. Microorganisms free from dust particles are found in indoor and outdoor air. A damp atmosphere contains fewer microorganisms than a dry atmosphere because the contaminants are carried down by the moisture droplets. Hence, the cold store air is usually free from microorganisms.
Method of Prevention
- Maintain the air humidity level inside the cleanroom.
- Operators should move as much as less inside the cleanroom.
- Aseptic rooms are maintained at higher differential air pressures than adjacent controlled areas.
- Air filtration and air change rates should be set to ensure that the defined cleanroom class is attained.
- Airflow over critical areas should be uni-directional (laminar flow) at a velocity sufficient to sweep particles away from the filling/closing area.
- Ultraviolet airlocks and door barriers must be used to separate areas of unequal risk.
- The air pressure of the changing room should be negative with regards to the manufacturing area corridor, but positive relative to external adjacent areas.
- Possible ventilation dampers, filters, and other services are designed and positioned in such a way that they are accessible from outside the manufacturing areas for maintenance purposes.
- All rooms and surfaces should be maintained and monitored for viable and non-viable particulates and the facility must be recertified on a semi-annual basis.
- HEPA filtered air should be blown evenly to the entire cleanroom. The airflow must be uniform in velocity and direction throughout any given cross-section of the area.
- The air velocity should be 100 ± 20 ft/min.
- The vertical flow from ceiling-mounted HEPA filter units is utilized to protect critical sections of processing lines as well as workbenches.
Operator
Operators are also another source for microbial contamination like the skin, hair, and clothing of the operator. Skin mainly contains microorganisms like staphylococci, lipophilic yeast, and dermatophytes fungi. Health and hygiene conditions also play an important role in microbial growth. The skin coliforms and other intestinal bacteria grow in poor health conditions. Open wounds are also the sources of saprophytic and pathogenic microorganisms. Further, the nasal passages also contain staphylococcus species. Some other reasons for contaminations are like lack of training, malpractices like eating foods, drinking beverages in the storage and processing areas.
Method of Prevention:
- Access to production areas must be controlled to ensure entry is restricted to trained personnel only.
- A high level of personnel hygiene must be observed.
- All inexperienced workers whose activities may affect the quality of the product must receive regular training, including hygiene instructions.
- Every person entering the manufacturing area should wear protective attire (over garments, hair cover, beard or mustache cover, overshoes) appropriate to the operations to be carried out.
- Direct contact should be avoided between the operator’s hand and exposed products or any part of the equipment that comes into contact with the product.
- Personnel access must only be made via changing rooms.
- Materials access must be via specified routes – generally via airlocks.
Raw Materials
The raw materials used for production can be a potential source of contamination. The main reasons for contamination from the raw materials due to storage and handling mistakes causing mix-ups or selection errors, contamination with microorganisms or other chemicals, degradation from exposure to excessive environmental conditions (such as heat, cold, sunlight, moisture), improper labeling, sampling, and testing, etc. Water also plays a major role in the microbial contamination. It acts as a carrier of all kinds of microbes.
Method of Prevention:
- Raw materials should be stored in a proper dust-proof area with proper labeling.
- Water used in the manufacture of pharmaceutical products should be suitable for the intended use and should be of pharmaceutical grade, microbiologically controlled, and monitored.
- Steam used for cleaning and sanitization of production tools and equipment, supply for autoclaves and humidification must be clean and free of additives.
Building
The buildings and manufacturing facilities may also contribute to the contamination. The main reasons for contamination due to facility issues like insufficient size and inadequate organization of the space, cross-contamination between consumables, raw materials, in process materials, and finished products, inadequate filth and pest controls, rough floors, walls, and ceilings, lack of air filtration systems, improper lighting and ventilation and inadequate washing, cleaning, toilet, and locker facilities, cleaning facilities and equipment.
Method of Prevention:
- Interior surfaces, e.g. floors, walls, ceilings should be smooth, free from cracks, and should permit easy and effective cleaning.
- Windows/viewing panels should be non-opening, flush with the wall panels, and properly sealed to prevent the collection of dust and microbial material.
- Pipework, ventilation, and light points should be designed to avoid the creation of recesses which are difficult to clean.
- Sinks within the production areas should be made of stainless steel.
Equipment
The types of equipment and other accessories that are used in processing, holding, transferring, and packaging are the common sources of microbial contamination. The main reasons for contamination from the equipment are inappropriate design, size, material leading to corrosion and accumulation of static material and/or adulteration with lubricants, coolants, dirt, and sanitizing agents, etc., improper cleaning and sanitization, design preventing proper cleaning and maintenance, irregular service, and deliberate use of defective equipment.
Method of Prevention:
- Areas must be regularly cleaned and disinfected.
- A high level of cleansing and hygiene should be practiced for the manufacture of the drug product.
- A suitable grade of cleaning agents should be used to minimize health risks.
- Contact time, application, temperature, mechanical action, and the chemistry of the cleaning agents should all be considered during the design of the cleaning process.
- Materials used for cleaning should not come in direct contact with the product.
- Validation of cleaning practices must be carried out to provide evidence that the process is effective in controlling microbial contamination.
Packaging and Manufacturing Process
Another way of contamination is the packaging materials throughout the manufacturing process. The main reasons for contamination during the manufacturing process include lack of dedicated facilities to manufacture a single product, inappropriate cleaning in-between batches to minimize the number of product changeovers, use of an open manufacturing system exposing the product to the immediate room environment, inappropriate zoning, absence of an area line clearance according to approved procedures and lack of cleaning status labeling on all equipment and materials used within the manufacturing facilities.
Method of Prevention:
- Flexible packaging used to inactivate microorganisms associated with foods include controlled atmosphere, vacuum, modified atmosphere, active, and edible packaging.
- The combination of rigid packaging materials made from metal, glass, or plastic with heat provides the most effective and widely used method for inactivating microorganisms.
- The manufacturing process should maintain proper hygienic conditions.
Make sure you also check our other amazing Article on : Laminar flow Equipment
