This document discusses control of microbial contamination in sterile and non-sterile pharmaceutical products. It defines sterile products as those that are free of viable microorganisms, including injectables, ophthalmic preparations, and diluents. Non-sterile products include tablets, ointments, and topical preparations. Sources of contamination are described as external air, personnel, surfaces, and water. Principal sterilization methods include thermal sterilization techniques like moist and dry heat as well as non-thermal methods like filtration, radiation, and chemicals. The document outlines various control measures for microbial contamination including environmental controls, compounding and processing practices, and concludes that supervision and adherence to proper procedures are necessary to maintain sterility.

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2. “CONTROL OF MICROBIAL
CONTAMINATION IN STERILE AND
NON-STERILE PRODUCTS”
PREPAIRED BY:
MR. RAKSHIT KESTWAL
11711179
SEPTEMBER 2017
2

3. TALK ABOUT.
Definition
Principle methods of
Sterilization
Control Measures for
Microbial Contamination
in Pharmaceutical
Products 3

4. STERILE: free from any living viable
germ or microorganisms; aseptic.
Sterile products: These are the dosage
form of therapeutic value which is
extremely free from viable
microorganisms.
Categorized as:
 Parenteral products
 Ophthalmic products
 Irrigating preparations 4

5. Continued…
Examples include:
Injectable (intravascular, intramuscular, subcutaneous,
intradermal and intraperitoneal)
Diluents for injectable (water for injection, sterile water,
purified water )
Vaccines
Ophthalmic preparations (eye drops, nasal drops)
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6. Examples include:
 Tablets (compressed, coated, effervescent, etc.)
 Ointments
 Syrups
 Oral suspensions & emulsions
 Transdermal/Topical patches
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Non-sterile products: These are those dosage
forms, which are other than sterile preparation like
oral and topical preparation.

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Sources of microbial contamination:
External atmospheric air inside the room
Personnel contamination
Surface contamination
Water contamination

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Principle methods of sterilization:

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Thermal Methods:
 Moisture Content
 Temperature
 Period Of Exposure.
As the temperature is increased time required to
produce a sterile state is decreased.
Thermal method of sterilization is further sub divide
into:
Dry heat
Moist heat
Continued…

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Dry heat:
Those substances which get degraded at a temperature range
of approximately 140ºC.
Contact for two hour at 180ºC or at 260ºC for 45 minutes can
produce killing of all kinds of bacteria and there spores.
Dry heat sterilization can be achieved by:
Hot air ovens
Dry heat tunnels

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Moist Heat:
In thermal sterilization rather than dry heat moist heat is
considered more efficient.
However it should be made into consideration that moist
heat cannot terminate pyrogens.
Moist heat sterilization can be achieved by:
Autoclave
Air steam mixture

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Non Thermal Methods of Sterilization:
It is also known as cold sterilization or non-thermal
method of sterilization.
Further Classified as:
 Physical method
 Chemical method

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Physical Sterilization methods:
It can be further classified as:
Radiation sterilization
Filtration sterilization
.

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Radiation sterilization
(a) Ultraviolet light: For the sterilization of
contamination in atmosphere and on surfaces,
ultraviolet light is usually employed.
(b) Ionizing radiations: These are the radiations
of elevated energy which are emitted from
radioactive isotopes like caesium-135 (gamma
rays) or by highly accelerated electrons at higher
velocity (cathode ray & β-ray)

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Filtration sterilization:
It is a complete method which persuades the
exclusion of particles, as well as microorganisms
beyond a confident size, from solutions and gases
without the use of heat.
Eg: Membrane filters.

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Descriptive Diagram of Membrane Filter:
Continued…

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Chemical Method of Sterilization:
Gas sterilization:
Gases like formaldehyde and sulfur dioxide are been
use from many years for sterilization purpose.
These chemicals are very reactive and sometimes are
very difficult to remove from surfaces
after exposure thus have very limited use only.

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Few examples:
 Alkylating gases: Ethylene oxide, propylene oxide,
formaldehyde and β-propiolactone.
 Oxidizing gases: hydrogen peroxide, ozone, per-
acetic acid and calcium dioxide.
Continued…

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Control Measures for Microbial
Contamination in Pharmaceutical
Products:
 Environmental Control
 Housekeeping
 Disinfection on Surface
 Control on Air
 Control on Personnel
 Compounding Of Products
 Processing By Automation

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Environmental Control:
 Strict physical and biological
environment control must be
maintained.
 High standard of cleanliness
should be maintained in the
clean-up and packaging areas
other than daily routine
disinfecting procedures.

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 Environmental control could more easily be achieved
were the movement of supplies and personnel is
smooth and strategically planned.
Continued…

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Continued…
Flow of Material in a Manufacture Unit

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Housekeeping:
 All the equipment should be
thoroughly cleaned at the end
of the day so that no pollutant
could be recognized after the
finished development.

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 All the housekeeping tools must be selected as per
there productivity and liberty from lint generating
affinity. They should be reserved for aseptic areas
only.
Continued…

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Disinfection on Surface:
After complete cleaning procedure all the surfaces of the
production unit must go for disinfection at least in aseptic
area, by spraying an effective liquid disinfectant followed
by wiping on all surfaces and with ultraviolet radiation
exposure.

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 Use of more than one pre-
filter total elimination of
profoundly polluted air.
 HEPA filters are employed.
It is 99.97% effective to
eliminate particles of 0.3μ
and bigger size particles.
Control on Air:

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 Laminar air flow principle has upgraded the
effectiveness of environmental control of aseptic
area to achieve class 100 area. This means there
are not more than 100 particles in the air of 100
cubic foot area with 0.5μ or more in size.
Continued……

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Laminar air flow bench:Continued…

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 All the employees must examine for their good
health and must be subjected to regular physical
examination.
Control on Personnel:

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 Sterile overalls, hoods, face mask and shoe
covers are the different component of apparel
worn by a personnel entering in sterile area.
 A preparatory procedure must be followed by
the personnel while entering in aseptic area.
Continued…

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 Machine can be developed to carry out certain procedures
and functions more efficiently, accurately and precisely
then a human.
 Moreover the biggest advantage is the infection caused by
human body as a source of biological contamination.
Processing By Automation:

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STERILITY TESTING:
The sterility testing is conducted for the detection of
any possible viable microorganism in any preparation.
Sterility Testing Could be Done by:
Membrane Filtration Method or by
Direct Inoculation Method

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 depending upon the nature of the product ie., liquid
filterable aqueous preparations, alcoholic and oily
preparation or preparation which is soluble in
aqueous or oily solvents provided these solvents do
not have any anti-microbial action can be sterilized
by membrane filters.
 Whereas creams, ointments, and solid dosage forms
are analyzed by direct inoculation method.
Continued…

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 Sterilization and control of microbial contamination
is a constant process.
 Sterilization and disinfection must be performed on
daily basis.
 Personnel performance and handling has a critical
and direct impact on contamination.
CONCLUSION

35.  Supervision and direction must be provided to the non-
professional workers, since they have direct involvement
with production of products.
 Suitable procedures and precautions must be followed at
all times.
 Control over all the environmental factors must be taken.
 Similarly during dispensing, filling and sealing, sterility
must be highly maintained.
Continued…
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Bibliography:
1. Lachman., Lieberman., 2013. The theory and practice of
Industrial pharmacy, fourth edition. Anwar,M., Warsi,MH.,
Jain,N., et’al .,ed. Sterilization. CBS Publishers &
distributors Pvt. Ltd, New Delhi. 804-827.
2. Sandle, T., 2011.A Review of cleanroom micro-flora:
Types, trends and patterns PDA J Pharm. Sci. Technol., 65
(4): 392 – 403.

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3. Nagarkar, P., Ravetkar, S.D. and Watve, M.G. 2001.
Oligophilic bacteria as tools to monitor aseptic
pharmaceutical production units. Appl. Environ.
Microbiol., 67(3):1371 – 1374.
4. Atasi, K., 2016. Membrane Technology Advances
Wastewater Treatment and Water Reuse[online],
Available:cdmsmith.com/enUS/Insights/Viewpoints/M
embraneTechnologyAdvancesWastewaterTreatmentan
dWaterReuse.aspx.

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5. Lachman., Lieberman., 2013. The theory and practice
of Industrial pharmacy, fourth edition. Anwar,M.,
Avis,KE., Jain,N., ed. Sterilization. CBS Publishers &
distributors Pvt Ltd, New
Delhi. 828-871.

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