Pharmaceutical Microbiology and its importance

 

Pharmaceutical Microbiology and its importance

                                   Anup Bajracharya

Microbiology is the scientific study of microorganisms such as bacteria, archaea, algae, fungi, protozoa, viruses, and certain helminths. This field focuses on understanding their structure, functions, classification, and the methods used to either utilize or regulate their behavior. When the principles, methods, and knowledge of microbiology are specifically applied to pharmaceutical processes, it becomes known as Pharmaceutical microbiology.

Pharmaceutical Microbiology is the applied science concerned with the study of microorganisms that are involved in:

• the production of pharmaceutical products,
• ensuring their safety,
• maintaining their quality and sterility,
• and preventing microbial contamination during drug development and production.

Pharmaceutical Microbiology can be defined as the study of microorganisms that are pertinent to the production of antibiotics, enzymes, vitamins, vaccines, and other pharmaceutical products; it also incorporates the study of microorganisms that cause pharmaceutical contaminations, and degradation, deterioration and spoil of pharmaceutical raw materials and finished products.

Importance of Pharmaceutical Microbiology

Pharmaceutical Microbiology is a vital discipline that plays a key role in ensuring the safety, quality, and effectiveness of pharmaceutical products. It is essential across every stage of drug development and production.

1. Production of Antibiotics, Vaccines, enzymes etc

Microorganisms are used in the development and production of antibiotics vaccines, enzymes, monoclonal antibodies, etc. It ensures biosafety and purity of these biological products.

·    Production of antibiotics- The most important use is the production of antibiotics, two third of antibiotics are produced from microorganisms. The pharmaceutical microbiology concerns with the isolation of antibiotic producing microorganisms from natural environments such as soil or water and use them for production of antibiotics through the process of fermentation. Thus, Microbiology helps in strain selection, fermentation monitoring, and antibiotic potency testing.

Production of vaccines- A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

Vaccines are often made from killed or weakened (attenuated) microorganisms, or specific components like proteins or toxins. Pharmaceutical microbiologists help to

• Select the right strain of bacteria or virus.
• Grow them in optimal culture media under controlled conditions (e.g., temperature, pH, aeration). Example: Using Salmonella typhi Ty21a strain for oral typhoid vaccine production.

 

·    Production of Enzymes-Microbial cells also produce intracellular and extracellular enzymes like amylase, proteases, lipases, invertase etc. Enzymes are collected either from the culture medium (extracellular enzymes) or from microbial cells (intracellular enzymes).

Examples- Amylase, protease, and lipase: Included in digestive formulations for patients with poor digestion. Streptokinase and urokinase helps to dssolve blood clots (used in heart attack treatment).Glucose oxidase is used in glucose biosensors for diabetics. DNA polymerases from Thermus aquaticus (Taq polymerase) is essential in PCR (Polymerase Chain Reaction) for genetic testing and disease diagnosis.

 

·     Production of Alcoholic products- Many microbial cells convert raw materials or substrates into valuable organic compounds such as butanol, ethanol, acetone etc. The production of alcoholic beverages and products is achieved through fermentation, a metabolic process in which microorganisms—mainly yeasts and bacteria—convert sugars into alcohol (ethanol) and other byproducts like carbon dioxide.

·      Production of Probiotics – Probiotics are live bacteria that may confer a health benefit on the host. Fuller in 1989 described probiotics as "live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance
Lactic acid bacteria (LAB) and Bifidobacteria are the most common types of microbes used as probiotics, but certain yeasts and bacilli may also be used. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures, such as in yogurt, soy yogurt, or as dietary supplements.

 

2. Sterility Testing

Sterility testing is a critical quality control process used to ensure that sterile pharmaceutical products such as injectables, ophthalmic solutions, and surgical implants are completely free from any viable microorganisms. This test is especially important for products that are introduced directly into sterile areas of the body, like blood, eyes, or tissues, where even a single contaminating microbe can cause severe infection or sepsis. The process involves incubating samples of the product in specially prepared culture media, such as Fluid Thioglycollate Medium (FTM) and Soybean-Casein Digest Medium (SCDM), under controlled conditions for at least 14 days to observe microbial growth. For instance, an intravenous infusion must undergo sterility testing to confirm that it does not contain any bacteria or fungi before it can be released to the market.

3. Microbial Contamination Control

Microbial contamination control is essential for non-sterile pharmaceutical products like tablets, capsules, syrups, creams, and ointments, which may be exposed to the environment during manufacturing and packaging. This process involves regular environmental monitoring, personnel hygiene checks, and testing of raw materials, in-process materials, and finished products. The goal is to prevent the presence of objectionable microorganisms, such as Escherichia coli, Pseudomonas aeruginosa, and Salmonella species, which can cause infections or degrade the product. For example, Pseudomonas aeruginosa in a topical ointment could infect wounds and delay healing, hence its presence is unacceptable in such formulations. Microbial contamination control ensures that the microbial content stays within acceptable limits and does not pose health risks to patients.

4. Microbial Limit Testing

Microbial Limit Testing (MLT) is used to determine the total number of viable aerobic microorganisms—both bacteria and fungi—present in a non-sterile pharmaceutical product. This test helps assess whether the microbial count falls within acceptable limits defined by pharmacopeias (like USP, BP, or IP). MLT consists of two components: Total Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC). Additionally, it includes specific tests to detect pathogenic organisms, such as E. coli, Salmonella, and Staphylococcus aureus. For example, a cough syrup might be tested for its total microbial load to ensure it contains fewer than 100 colony-forming units (CFU) per mL of bacteria and fewer than 10 CFU/mL of fungi, ensuring it is safe for oral consumption. MLT is crucial for maintaining the microbial quality of non-sterile products.

5. Preservative Effectiveness Testing (PET)

Preservative Effectiveness Testing, also known as antimicrobial preservative effectiveness testing, is performed to verify that the preservatives added to multi-use pharmaceutical products are effective enough to prevent microbial growth during storage and usage. This is especially important in products like eye drops, nasal sprays, creams, and syrups, which may be repeatedly exposed to air or come into contact with users. In this test, the product is intentionally inoculated with known microorganisms (e.g., Staphylococcus aureus, Candida albicans, Aspergillus brasiliensis) and observed over time to see whether the preservatives can eliminate or significantly reduce microbial growth. For instance, in a multi-dose eye drop, PET ensures that if bacteria are accidentally introduced during usage, they will not multiply and compromise the product's safety.

6. Plays a Role in Innovation

Pharmaceutical microbiology helps in the discovery of new antimicrobial agents and in developing rapid diagnostic techniques.

It is important for addressing antibiotic resistance and ensuring the continued effectiveness of medicines.

 Note-

The exploitation of microorganisms and their products has played an increasingly prominent role in the diagnosis, treatment and prevention of human diseases. The nonmedical uses are also of significance, Example, the use of bacterial spores (Bacillus thuringiensis) and viruses (baculoviruses) to control insect pests, the fungus Sclerotinia sclerotiorum to kill some common weeds, and improved varieties of Trichoderma harzianum to protect crops against fungal infections.

·    Diagnosis of diseases and treatment- Different tests are used to detect infectious microorganisms like ELISA, Widal test. Antimicrobial Susceptibility testing is mainly used for selection of antibiotics for the treatment of microbial infections.

·       Apart from drugs and bio products development, microbiology contributes towards quality control of a pharmaceutical laboratory. Regular environmental monitoring in manufacturing areas ensures early detection of contamination sources. Personnel hygiene monitoring ensures that staff do not introduce harmful microbes into clean areas.

References

1. Denyer, S. P., Hodges, N. A., & Gorman, S. P. (2004). Hugo and Russell's Pharmaceutical Microbiology (7th ed.). Blackwell Publishing.
2. WHO. (2002). Guidelines on Good Manufacturing Practices for Pharmaceutical Products. World Health Organization.