Microbial Contamination in Pharmaceutical products
What is Microbes?The microorganism or microbes is a microscopic organism which may exist in single celled form or in a colony. Single celled microorganism were in the first form of life.Microorganism can almost found everywhere on the earth. The science where microorganism are studied called Microbiology.
- At the product development stage
- Routine monitoring of pharmaceutical environment & people
- Critical utilities i.e. Water system, compressed air system
- Raw material
- Equipment design
- Facility design
A glimpse of USFDA-Drug Recal considering Microbial Contamination
The majority of a drug recall initiate due to impurity, lack of sterility assurance, particulate matter and microbial contamination.
|Year||Total Drug Recall||Due to Microbial Contamination||% Contribution of Microbial Contamination|
Source of Microbial contamination
In pharmaceutical, there are many sources of microbial contamination but out of all source, people are the main source of microbial contamination who carries lots of microbial loads and knowingly and unknowingly introduce the contamination into drugs products. Rest of the microbial contamination given below;
Poor Facility Design– No proper segregation for man and material, the improper differential pressure between two adjacent rooms, no temperature or humidity control, or inadequate design.
Poor design of equipment – Common mistakes which are generally made in pharmaceutical during procurement of equipment we have not to consider hygiene design of equipment. In URS of equipment, we generally covered operating requirements, safety requirements, a regulatory requirement but we forgot to address the hygiene design requirement of equipment which results in a lot of batch failure in the future. During equipment user requirement finalization we have to cover the following hygiene design aspect; No dead leg & crevice, No hard to clean surface, roughness value, considered sanitary valve, etc.
Inadequate Cleaning and sanitation procedure– A validated cleaning and sanitization procedure of equipment and area should be in place to control microbes and all the disinfectant and their concentration which are used in the area and on equipment should be validated before use. At least one sporicidal disinfectant should be incorporate in the disinfectant and sanitization program to avoid the germination of spores inside the processing area. Disinfectant validation is also required before using any disinfectant into the GMP area
Poor gowning– If any gown not covered full body then it microbes can be entered into the product from all these uncovered areas so proper gowning, gloves, mask, and headgear is required before entering into the processing area where the product gets exposed
People– Fast movement of people inside the manufacturing area can generate lots of particle/ microbes which can further deteriorate the drug products.
Raw material – Sometimes raw material itself has a lot of microorganisms due to its nature like if the raw material sources are natural or mined then definitely there will be a lot of microorganisms and if there is no microorganisms reduction process (like high temperature/ reduction of water activity/ >20% alcohol />3% Hydrogen Peroxide) in the finished goods preparation then the use of these materials will definitely contaminate the finished products. So considering all these facts, raw material microbial assessment is very much required before using the same into the formulation and if microbial reduction process can not apply on the raw material then the formulation process of finished goods should have a microbial reduction process /have any robust preservative system or have pH <3 or >10.5.
For the microbial assessment of any raw material following thing should be reviewed;
Manufacturing process: Is the manufacturing process of raw materials subject to antimicrobial treatment or raw material itself have antimicrobial property.
Water activity of material: if water activity is <0.6 then chances of microbial proliferation is very low
pH – in case of liquid material: If pH <3 or >10.5 then it mean material is not microbial susceptible
Nature of Material: Is the material nautruarl / mined mean its microbial susceptible.
Basis above assessment, some microbial testing should be done in raw materials.
Utilities: Major utility for any product is water and water is the main source of microorganism so in that case regular microbial monitoring of the water should be done to ensure its quality. Apart from that, some gases are also used in the process so filtering of the gases through a 0.22-micron filter before coming into the product contact is required to avoid any microbial contamination and there should be periodic validation of gases and filter replacement frequency should be in-place.
So take care and consider all the above points to avoid any microbial contamination in the drug products.
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