Sources and types of microbial contaminants in Pharmaceutical Products.



  • In our environment microbes are present everywhere i. Air, water, soil etc.

  • These microbes are to cause spoilage of not only food products but also pharmaceutical products.

  • The spoilage of pharmaceutical products can result in serious health hazards to the consumers as well as cause financial problems to the manufacturers.

  • Pharmaceutical products are considered microbiologically spoiled when even low levels of pathogenic microbes or toxic microbial metabolites are present and detectable physical or chemical change have been noted in the product.

  • In short microbial spoilage of pharmaceuticals can be defined as deterioration of pharmaceutical products due to microbial contamination.

Sources and Types Of Contamination:

  • Contaminants can gain entry into a production process stream from several sources such as, 

    • Personnel, 

    • Poor facility design, 

    • Incoming ventilation air, 

    • Machinery and other equipment for production, 

    • Raw material and semi-finished material, 

    • Packaging material, 

    • Utilities, 

    • Different media used in the production process as well as for cleaning and Cleanroom clothing.

  1. Working Environment:

  • Air is not a natural environment for microbes to grow as it does not contain water and nutrients needed for the growth.

  • However the microbes are carried into the atmosphere and remain suspended on particles of dust, skin, clothing, moisture or nasal droplets, sputum following sneezing or coughing.

  • The microbial load of the air may get increased during handling of contaminated materials during dispensing, blending and formulation processes.

  • Use of starch and sugars in dry state may increase fungal counts.

  • Settle plate and different air sampling methods are commonly used for isolation and identification of microbes present in the working environment.

  • Microbes which are commonly isolated from atmosphere are, Staphylococcus species, Streptococcus spp., Bacillus spp., Microsporum spp., Aspergillus spp., Penicillium spp. etc.

  1. Personnel:

  • Personnel who are supervising or performing drug manufacturing or control can be a potential source of microbiological contamination and a vector for other contaminants like,

    • Natural skin flora of microorganism can be a main source of contamination e.g. Staphylococcus aureus, Sarcina spp., Alcaligenes spp. Etc, various dermatophytic fungi viz. Epidermophyton spp., Microsporum spp. etc.

    • If persons having wound they may support organisms like, Staphylococcus aureus, Staphylococcus pyogenes, Proteus spp., Pseudomonas aeruginosa etc.

    • The respiratory discharge of the personnel may include organisms like, Staphylococcus aureus, Staphylococcus salivarius, Neisseria pharyngis, Klebsiella pneumoniae etc.

  • The main reasons for contamination from the personnel include:

    • Lack of training

    • Direct contact between the operator’s hands and starting

    • materials, primary packaging materials and intermediate or bulk product

    • Inadequate personnel cleanliness

    • Access of unauthorized personnel into production, storage, and product control areas

    • Inadequate gowning and personnel protective equipment, and

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

  1. Buildings and Facility:

  • The buildings and manufacturing facilities may also contribute to the contamination.

  • Walls and ceilings of building are sources commonly for Aspergillus spp., Cladosporium spp., Penicillium spp., Bacillus spp. etc. They are mainly found in poorly ventilated buildings.

  • These microorganisms utilize the contents of the wall paint as nutrients.

  • The other reasons of contamination due to facility issues include:

    • Inadequate filth and pest controls.

    • Rough floors, walls and ceilings.

    • Lack of air filtration systems.

    • Improper lighting and ventilation.

    • Poorly located vents, and drains.

    • Inadequate washing, cleaning, toilet, and locker facilities to allow for sanitary operation, cleaning of facilities, equipment, and utensils; and personal cleanliness.

  1. Equipments:

  • The equipment and utensils used in processing, holding, transferring and packaging are the common source of pharmaceutical contamination. 

  • The main reasons for contamination from the equipment include:

  • 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.

  • Design prevents proper cleaning and maintenance.

  • Improper calibration and irregular service, and

  • Deliberate use of defective equipment.

  1. Materials:

  • The raw materials used for production can be a potential source of contamination.

  • Animal origin raw materials like gelatin, thyroid, pancreas and Plant origin products like starch, acacia tragacanth etc. are known sources of microbial contamination.

  • Raw materials of mineral origin are usually free from microbes while some like zinc oxide, calamine, bentonite may contain spores of Clostridium spp.

  • The main reasons for contamination from the raw materials include: 

    • 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, etc.

    • Improper labelling.

    • Improper sampling and testing, and 

    • Use of materials that fail to meet acceptance specifications.

  1. Manufacturing Process:

  • There are various opportunities for contamination of raw material, intermediates or packaging materials throughout the manufacturing process. 

  • The main reasons for contamination during manufacturing process include: 

    • Lack of dedicated facilities to manufacture a single product 

    • Inappropriate cleaning in-between batches to minimize the amount 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 following each cleaning process and between each batch, and

    • Lack of cleaning status labelling on all equipment and materials used within the manufacturing facility.

  1. Water:

  • Water is one of the main constituents of many preparations and is also needed for washing and many processes.

  • Fresh water contains many microbes, while water contaminated with sewage waste contains microbes of Proteus spp., Escheresia spp., Clostridium spp., Streptococcus species, Flavobacterium spp. etc.

  • Softened water is commonly used for washing purposes in industry, microbes from Bacillus and Staphylococcus spp. May come in during the process.

  • Water for industrial use may be treated with filtration or uv or stored at elevated temp. To discourage microbial growth in it.

  1. Packaging:

  • The packaging of pharmaceuticals plays a dual role; it holds the product and also prevents it from spoilage.

  • The materials used for pharmaceutical labelling and packaging contains many species of microbes like Bacillus, Clostridium, Penicillium etc.

  • The containers and closures are needed to be sterilized before use.

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