GMP module 07 - Overview of Microbiology Tests

Outcome of the Module:

Microorganisms are a group of organisms that include bacteria, moulds, yeasts, and viruses. They are also very adaptable and can live and multiply in conditions where other living things cannot survive. Microorganisms are also naturally all around us in the environmental air and on our skin. Microbiology tests ensure the absence of pathogens in raw materials and water, on packaging, and on production equipment.

Microbiology is the scientific study of microscopic organisms, often called “micro-organisms” or “microbes”. Although micro-organisms are small, the mass of microbial life on earth is 25 times greater than the total mass of animals. The external surfaces of all animals and plants are covered with micro-organisms, not to mention animals’ internal surfaces. The human body contains about 100 trillion microorganisms.

This module introduces you to the world of micro-organisms and the potentially bad effects they can have on the products you help to manufacture. The module also introduces you to the methods needed to control micro-organisms.

At the end of this module, you will be able to:

  • Describe what types of micro-organisms may be found in pharmaceutical products, water, and the environment
  • Identify the major sources of microbial contamination and what is considered to be “objectionable”
  • Identify microbial contamination problems in the workplace
  • Identify procedures to reduce the chance of microbial contamination

Part I: Bacteria and Fungi

Medicine is taken when a person isn’t well, has a disease or infection, or has a problem with their immune system. These conditions make people more vulnerable to microbial infection, and therefore, consuming products that have contamination may make them sicker.

We do know, though, that certain products are more at-risk than others. For example, sterile products must have zero-allowed bio burden; topical and intranasal products may only have low bio burden; and oral liquids and dry solid products have less restricted bio burden.

The cGMPs also require manufacturers to keep potential bio burden contamination below very strict levels.

In the pharmaceutical industry, the major types of micro-organisms of concern are bacteria and fungi. Manufacturers of biological products are also concerned with the presence of viruses in their products.

Some species of bacteria are very hardy. They can live in extremely harsh environments, such as in high salt concentration, acids, or high temperatures. Manufacturers need to control these micro-organisms to ensure that they stay at acceptable levels. Micro-organisms higher than acceptable levels may harm the products or consumers.

Micro-organisms are essential for your health. The normal flora that covers your skin and internal surfaces prevent disease-causing micro-organisms from taking over.

Bacteria and fungi play a vital in the decomposition of all organic matter, returning carbon, nitrogen, and other essential elements back to the soil.

Bacteria and fungi also play important roles in industry, for instance, in the production of food, vaccines, and antibiotics. Probiotic bacteria, which can be found in yoghurt, helps the body remove cholesterol. Yeasts, a type of fungus, are used in the production of bread and alcohol. Moulds, another fungus, make penicillin.

Of the several thousand bacterial and fungal species known, only relatively few commonly cause disease. Others are “opportunistic” and infect people when they are immunocompromised (sick or run-down). Infections such as sore throats, tetanus, cholera, and tuberculosis are caused by bacteria. Some fungal species are responsible for the deterioration of textiles and wood, while others cause diseases like athlete’s foot and thrush.

Part II: Growth of Microbes

Micro-organisms can rapidly multiply in the presence of stagnant water. This is why equipment must be stored dry.

In addition, topical creams have strict limits on bio burden, since creams are often used by patients on damaged or broken skin. If the product is contaminated, patients may become infected.

To properly control micro-organisms, we need to understand what makes them grow and multiply.

Micro-organisms only need small amounts of nutrients and moisture to grow, which is why manufacturing facilities need to be kept clean and dry.

The growth of micro-organisms depends on the combination of the below factors:

  • Nutrients
  • Moisture
  • Physical environment

Bacteria multiply by a process known as binary fission. This means that each bacterial cell pides into two living cells so that the population doubles in number with each pision.

The population of bacteria is said to grow exponentially, and will continue to expand until the nutrients run out or environmental conditions change.

To multiply, bacteria usually require:

  • Moist conditions
  • Adequate temperature
  • Adequate nutrients
  • No inhibiting agents

 

Part III: Micro-organism Control

Micro-organisms are mostly killed by exposure to heat above 55 – 60°C for periods of time. The heat breaks down the cell wall, which kills the micro-organism. The cell walls of spores, however, are resistant to anything but high heat.

Similarly, alcohol is a good general sanitizing agent, but there are some micro-organisms that are not killed by alcohol (such as spores).

A combination of heat and alcohol provides two methods of sanitizing. Of course, sanitation will only be effective if a validated procedure is followed. Pay particular attention to:

  • Pre-cleaning to remove most of the chemical residues and bio burden
  • The length of time the heat and sanitizing agents are applied for: too short an exposure time will be less effective.

Some micro-organisms are of particular concern in certain dose forms. 

Objectionable organisms are organisms that shouldn’t be present in a product, because of:

  • Product degradant on, making products ineffective
  • Consumer safety, as products could become health risks

We cannot eliminate micro-organisms. But we can minimize their numbers, or exclude them from our manufacturing following lists a number of methods we use to minimize micro-organisms:

  • Control the manufacturing environment
  • Wear protective clothing
  • Implement cleaning and sanitation programs
  • Keep equipment clean and dry
  • Maintain room pressures by keeping doors closed
  • Maintain a high standard of personal hygiene

 

Part IV: Minimizing Micro-organism

cGMPs require manufacturers to minimize the numbers of micro-organisms from entering production areas and products. Typical ways this can be done include using air pressure differentials so that micro-organisms are precluded and ensuring that operators are appropriately gowned (e.g., hat, boots, cover-alls).

 Micro-organisms, particularly moulds and spores, are transmitted to rooms by air currents. Positive filtered air pressure in rooms prevents these contaminants from entering the rooms due to the air barrier.

 When products are exposed to the environment, the environment must be controlled. Some ways of achieving environmental control include the implementation of:

  • Air handling systems
  • Designated manufacturing zones
  • Cleaning programs

 

Air handling systems include ways to filter the air, for example, with the use of HEHA (high-efficiency particulate air) filters that trap micro-organisms in the air. The air handling systems should generally maintain positive air pressure relative to the outside environment in order to prevent particles and micro-organisms from entering the facility, and particularly the manufacturing areas.

 This is one of the main reasons that all doors should be kept closed.

 Cleaning programs at the facility should include keeping manufacturing areas clean and dry at all times, as well as regular checks and periodic cleaning of the air ducts and filters.

 In particular, surfaces that may catch dust should be regularly cleaned, such as ledges, door handles, piping, etc.

Conclusion:

This module provided an introduction to the control and management of manufacturing of pharmaceutical products.

Key points covered in this module:

  • Micro-organisms are very adaptable, and are found everywhere.
  • Micro-organisms need only small amounts of nutrients and moisture to grow, and they can grow very quickly.
  • Objectionable organisms should not be present in a product because they can reduce the product’s effectiveness and cause possible harm to consumers.
  • Although micro-organisms cannot be necessarily eliminated entirely, manufacturers need to keep micro-organisms at acceptable levels.
  • To reduce the numbers of micro-organisms in the workplace, there must be strict controls in place over the manufacturing environment, starting materials, equipment, pharmaceutical water, the environment, and personal hygiene.

 

Online Quiz:

Online Quiz:

  • Number of questions: 10
  • No time limit
  • Allow you save and finish at a later date
  • Allow you to go back and change your answer
  • Attempting each question is mandatory
  • Pass mark at and above 70%
  • Print results and certificates
DOWNLOAD COURSE