Most of the raw materials for pharmaceutical products support microbial growth based on the nutritive properties and moisture contents. Microbiological contaminants are infectious materials, such as bacteria, mold, fungi, and viruses. These contaminants are often found in food and water and cause serious illnesses. Deterioration of pharmaceutical products by the contaminant microbes is known as microbial contamination. These microorganisms cause product spoilage and result in loss of therapeutic properties. Various sources through which microbial contaminants gain entry are: the atmosphere, operators, raw materials from which products are manufactured, and equipments.
Atmosphere: Microbial growth in heating ventilation
and air-conditioning (HVAC) systems and their contamination of the indoor air
environment is a growing concern. A poor HVAC system is a potential source of
growth of microbes and a transportation mode for dispersing contaminants
throughout the manufacturing facility. The main reasons for contamination due
to HVAC issues include accumulations of organic material in or near HVAC air
intakes, ineffective filtration of the supply air, insufficient magnitude of
pressure differentials causing flow of reversal, erroneous ratio of fresh air
to recirculated air, inability to access ventilation dampers and filters from
outside the manufacturing areas and non-directional airflow within production
or primary packing areas.
Operators: The main reasons for the contamination
from the operators include mainly lack of training, Direct contact between the
operator’s hands and starting materials, primary packaging materials and
intermediate or bulk products, Inadequate cleanliness, access of unauthorized
operators into production, storage, and product control areas, malpractices
like eating food, drinking beverages, or using tobacco in the storage and
processing areas.
Raw materials: The raw materials used for production are
a potential source of contamination. 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 labeling, sampling, and testing.
Equipments: The equipment used in processing,
holding, transferring and packaging are the common source of pharmaceutical
contamination. The main reasons for contamination include inappropriate design,
size, material leading to corrosion and accumulation of static material,
coolants, dirt, and sanitizing agents, improper cleaning and sanitization,
design preventing proper cleaning and maintenance, improper calibration and
irregular service, and, Deliberate use of defective equipment etc.
Sources of Contaminants
• Air carrying dust: Dust is everywhere. Air is the
carrier of the dust particles. Very small dust particles that present inside
the aseptic room are the source of contamination. Hence, a HEPA filter is used
for the reduction of dust particles inside the room.
• Skin of the operators: The outer skin of the
operators should be smooth and covered properly. Any skin infections or rashes
are the sources of microorganism growth inside the room.
• Movement of persons inside the aseptic room: It is
advisable that movement of persons inside the aseptic room should be
restricted. It is evident that a person walking inside the room liberates 5000
bacteria/minute.
• Operator's health: Persons who are inside the
aseptic room, should be healthy and free from any infections. A single sneeze
will produce up to 1 million bacteria.
• Manufacturing process: The manufacturing process
generates contaminants. The main reasons for contamination during the manufacturing
process are the lack of dedicated facilities to manufacture a single product,
inappropriate cleaning in-between batches to minimize the number of product
changeovers, use of an open manufacturing system exposing the product to the
immediate room environment, inappropriate zoning, lack of cleaning status
labeling on all equipment and materials used within the manufacturing facility,
etc.
Types of Microbial Contaminants
Microbial contamination is broadly classified into direct
contamination and cross contamination (Flowchart).
(a) Direct contamination: Contamination occurs by
microbial components and poorly maintained heating, ventilation, and air
conditioning systems.
(b) Cross-contamination: It is the process by which
microbes are spread indirectly from one to another through improper and
unsterilized equipment.
Flowchart: Types of microbial contamination
Direct contamination is classified as follows:
(a) Direct Physical contamination: Examples: Particles, fibers,
metal parts, etc.
(b) Direct chemical contamination: Examples: Moisture,
gases, vapors, etc.
(c) Direct biological contamination: Example: Microorganisms
like bacteria, viruses, molds, fungi, etc.
Cross-contamination is classified as follows:
(a) Physical cross-contamination: Example: Leakage of oil
seal from the reactor.
(b) Chemical cross-contamination: Examples: Moisture content
is increased when a product is exposed to high relative humidity.
(c) Biological cross-contamination: Example: Improper
cleaning of equipment, unclean equipment used for the manufacturing process.
Types of Food Contaminants:
(a) Biological contaminants: Microbial contaminants are
responsible for food-borne diseases that are caused by bacteria, viruses,
fungi, parasites, biological toxins, etc. e.g.: Seafood toxins and mushroom
toxins.
(b) Chemical contaminants: Chemical substances that are
responsible for food-borne illness. e.g.: Toxic metals, Pesticides, etc.
(c) Physical contaminants: Any foreign substances that are
accidentally observed in the food. e.g.: Hair, wire, dust, sand particles, etc.
Some examples of contaminants in pharmaceutical products are given in the table.
Table: Contaminants for pharmaceutical products
|
Pharmaceutical products |
Contaminant |
|
Plague
vaccine |
Clostridium
tetani |
|
Serum vaccine
|
Staphylococcus
aureus |
|
Thyroid
tablets |
Salmonella Muenchen |
|
Antibiotic
eye ointments |
Pseudomonas
aeruginosa |
|
Talcum powder |
Clostridium
tetani |
|
Saline
solution |
Serratia
marcescens |
|
Antiseptic
mouth wash |
Coliforms |
|
Surgical
dressings |
Clostridium
species |
|
Hand cream |
Klebsiella
pneumoniae |