1. BENGAL COLLEGE OF PHARMACEUTICAL SCIENCES & RESEARCH, DURGAPUR Name:Ujjwal Kanti Pal Roll:24201920036 Year:2 ND Year Semester:3 RD Semester Subject:Pharmaceutical Microbiology Subject Code:PT-319 Topic:Source Of Contamination In Aseptic Area And Prevention Session:2021-2022 Submitted To:Ms. Sucharita Dutta

2. ASEPTIC AREA [1] 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 aseptic area. An aseptic area is a premise in a clean area, designed, constructed, serviced and used with an intention to prevent the microbial contamination of the product.

4. PROCESS FLOW DIAGRAM OF ASEPTIC AREA

5. SOURCE OF CONTAMINATION The source of contamination in an aseptic area are: 1. Atmosphere 2. Operator 3. Raw Materials 4. Buildings 5. Equipments 6. Packaging and Manufacturing Process

6. ATMOSPHERE Atmospheric gases namely oxygen (O 2 ) and carbon dioxide (CO 2 ) are the main sources for microbial growth. Oxygen has more significant effect on microbial growth. Dust particles in the outside air are the main carriers for the soil organisms. The microorganisms are also present in droplets expelled out from the mouth and respiratory track of human while talking, sneezing and coughing. Microorganisms free from dust particles are found in indoor and outdoor air. Damp atmosphere contains less microorganisms than the dry atmosphere because the contaminants are carried down by the moisture droplets.

7. METHOD OF PREVENTION 1. Maintain the air humidity level inside the clean room. 2. Operators should move as much as less inside the clean room. 3. Aseptic rooms are maintained at higher differential air pressures than adjacent controlled areas. 4. Ultraviolet air lock and doors barriers must be used to separate areas of unequal risk. 5. The air velocity should be 100 ± 20 ft/min.

8. OPERATOR Operators are also another source of microbial contamination in skin, hair and clothing of the operator. Skin mainly contains microorganism like staphylococci, lipophilic. Health and hygiene conditions also play an important role in microbial growth. Open wounds are also the sources of saprophytic and pathogenic microorganisms. Some other reasons for microbial growth are lack of training, malpractices like eating foods, drinking beverages in storage and processing area.

9. METHOD OF PREVENTION 1. A high level of personnel hygiene must be observed. 2. All in-experienced workers whose activities may affect the quality of product must receive regular training. 3. Personnel access must only be made via changing rooms. 4. Materials access must be via specified routes - generally via air locks. 5. Direct contact should be avoided between operator’s hand and exposed products or any part of the equipment that comes into it.

10. RAW MATERIALS The raw materials used for production can be a potential source of contamination. The main reasons for contamination from raw materials due to storage and handling mistakes causing mix-ups or selection errors, contamination with microorganism or other chemicals. Water also play an important role for the microbial contamination.

11. METHOD OF PREVENTION 1. Raw materials should be stored in proper dust proof area with proper labeling. 2. 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. 3. Steam used for cleaning and sanitization of production tools and equipment, supply for autoclaves and humidification must be clean and free of additives.

12. BUILDINGS The buildings and manufacturing facilities may also contribute to the contamination. The main reasons of contamination due to facility issues like insufficient size and inadequate organization of the space, cross contamination between consumables, raw materials, in-progress materials and finished products.

13. METHOD OF PREVENTION 1. Interior surface, e.g. floors, walls, ceilings should be smooth, free from cracks and should permit easy and effective cleaning. 2. Windows/viewing panels should be non- opening, flush with the wall panels and properly sealed to prevent collection of dust and microbial material. 3. Sinks within the production areas should be made of stainless steel. 4. Pipe work, ventilation and light points should be designed to avoid creation of recesses which are difficult to clean.

14. EQUIPMENT The equipments 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 adulteration with lubricants, coolants, dirt and sanitizing agents etc., improper cleaning and sanitization, design preventing proper cleaning and maintenance, irregular service and deliberated use of defective equipments.

15. METHOD OF PREVENTION 1. Areas must be regularly cleaned and disinfected. 2. A high level of cleansing and hygiene should be practiced for the manufacture of drug product. 3. Suitable grade of cleaning agents should be used to minimize health risks. 4. Materials used for cleaning should not come in direct contact with the product. 5. Validation of cleaning practices must be carried out to provide evidence that the process is effective in controlling microbial contamination.

16. PACKAGING AND MANUFACTURING PROCESS Another way of contamination is the packaging materials throughout the manufacturing process. The main reasons for contamination during manufacturing process includes lack of dedicated facilities to manufacture a single product, 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.

17. METHOD OF PREVENTION 1. Flexible packaging used to inactive microorganisms associated with foods include controlled atmosphere, vacuum, modified atmosphere, active and edible packaging. 2. The combination of the rigid packaging materials made from metal, glass or plastic with heat provides the most effective and widely used method for inactivating microorganisms. 3. Manufacture process should maintain proper hygienic condition.