SOURCES OF CONTAMINATION IN ASEPTIC AREA AND PREVENTION | S.Y B.PHARM SEM-III

 SOURCES OF CONTAMINATION

SOURCES OF CONTAMINATION IN PHARMACEUTICAL MANUFACTURING

CONTAMINATION: - Contamination, in broad sense, is the presence of minor unwanted particulate matter called contaminants in atmosphere, physical body, etc.

PHARMACEUTICAL CONTAMINATION: - Involves the introduction of microbes into pharmaceutical finished products.

THE MAIN SOURCES OF CONTAMINATION IN THE PHARMACEUTICAL INDUSTRY ARE: -

          1.     ATMOSPHERE

          2.     WATER (sources of water contamination)

          3.     RAW MATERIAL

          4.     PERSONNEL (SUPERVISORS, OPERATORS AND WORKERS)

          5.     EQUIPMENT

          6.     BUILDING

ATMOSPHERE: - Atmospheric conditions during manufacturing as well as during storage affect the quality of final preparation. The atmosphere is unable to support microbial growth but dust particles in outside air (originate from soil) may carry soil microorganisms. E.g. Bacillus spp, yeast and moulds. These microbes also occur in droplets expelled in to the atmosphere from the mouth & respiratory tract by talking, sneezing, and coughing.

Atmosphere in and around the industrial area contains potential contaminants like dust, silica, etc and gases like CO2, water vapors, etc and also contaminants microorganisms like P.aeruginosa, A.niger, etc. These contaminants may get incorporated into the end product either during the process of manufacturing or during purification.

PREVENTION: - The microbial count of air or atmosphere may be reduced by chemical disinfection, Ultraviolet light, Filtration and gaseous agents.

Prior to air entry into the working area, the air should be initially passed through a suitable prefilter then treated with an electrostatic precipitator and finally through HEPA filters. Periodic removal of air-borne dust settled on walls, floors and ceilings is essential.

WATER: - (sources of contamination of water)  Water is the most common solvent used in pharmaceutical industry, and it is the greatest source of contamination Although, it is deprived of most of the contaminants yet it contains pyrogens and traces of sulphates, chlorides and carbonates of Ca, Mg and Na.

Therefore, usage of water for washing the machineries and working areas may leave traces of these contaminants.

PREVENTION: - Almost all of the pharmaceutical operations should be carried out using purified water obtained upon deionization, distillation, ion exchange, reverse osmosis, filtration or other similar processes. For the preparation of parenterals, water for injection, sterile water for injection or bacteriostatic water for injection must be employed.

RAW MATERIALS: - The raw materials used for production can be a potential source of contamination.

The main reasons for contamination from the raw materials include:

Use of raw materials like powders (active ingredients and excipients) that fail to meet acceptance specifications.

Degradation of raw materials from exposure to excessive environmental conditions such as heat, cold, sunlight, moisture, etc.

Contamination of raw materials and excipients with microorganisms or other chemicals.

Storage and handling mistakes causing mix-ups or selection errors

Improper labeling and

Improper sampling and testing.

PERSONNEL (SUPERVISORS, OPERATORS AND WORKERS)

Personnel who are supervising or operating and working performing drug manufacturing or control can be a potential source of microbiological contamination. Personnel working in aseptic areas, if suffering from cold, allergies, dermatological conditions or any similar illness carry multiple microorganisms which upon expulsion into atmosphere via sneezing, coughing, talking etc., can lead to contamination.

The skin, hair and clothing of the operator are potent sources of microbial contamination. Poor personal hygiene can result in the presence of skin coliforms and other intestinal bacteria. Open wounds are a sourse of saprophytic and pathogenic microorganisms.

The main reasons for contamination from the personnel include:

Lack of proper training of supervisors, operators and workers.

Direct contact between the operator’s hands and starting materials, primary packaging materials and intermediate or bulk product

Inadequate personnel cleanliness and , if suffering from cold, allergies, dermatological conditions or any similar illness.

Inadequate gowning and personnel protective equipment, and

Malpractices like eating food, drinking beverages, or using tobacco in the storage and processing areas.

PREVENTION: - Personnel should be well trained and periodically evaluated in the principles of aseptic processing and techniques to be employed before participating in the preparation of sterile products.  A high level of personnel hygiene must be observed. Every person entering the manufacturing area should wear protective attire (over-garments, hair cover, beard or moustache cover, overshoes gloves, foot covers and even goggle to ensure complete coverage of all skin areas) 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 equipment that comes into contact with product. The entrance of most of the working areas is equipped with air blowers that aid in removing any loose dirt, lint from uniform of the operators.

EQUIPMENT: - The equipment and utensils used for formulation of pharmaceutical and used in processing, holding, transferring and packaging are the common source of microbial and particulate pharmaceutical contamination.

The main reasons for contamination from the equipment include:

The external surfaces of equipments are potential source of contamination due to sedimentation of particles and droplets from the atmosphere.

Inappropriate design, size, material leading to corrosion and accumulation of static material and/or adulteration with lubricants, coolants, dirt, and sanitizing agents

Improper cleaning and sanitization, calibration and irregular service, and deliberate use of defective equipment.

PREVENTION: - Equipments may be sterilized or disinfected by heat, gaseous, or chemicals.

Many tanks, containers, small equipments and reaction vessels are sterilized by steam under pressure (autoclave).

BUILDING: - The buildings and manufacturing facilities may also contribute to the contamination. The main reasons of contamination due to facility issues is insufficient size and inadequate organization of the space leading to selection errors like mix-ups or 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, poorly located vents, ledges, and drains, and, inadequate washing, cleaning, toilet, and locker facilities to allow for sanitary operation, cleaning of facilities, equipment, and utensils; and personal cleanliness.

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 collection of dust and microbial material. Pipe work, ventilation and light points should be designed to avoid creation of recesses which are difficult to clean. Sinks within the production areas should be made of stainless steel.