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Manufacturing
Introduction
To give an overview of the principles involved in the
manufacture of sterile products
The overall objective is to produce product that has a
high assurance of sterility (and which meets all other
quality parameters)
This presentation:
Summarises the general approach
Gives a framework for other detailed guides on specific aspects of
Fundamentals
This is a worst-case figure (with a challenge more resistant than product bioburden).
Real confidence levels are generally very much higher
A figure that has sometimes been quoted for aseptically filled product is probability of
non-sterility of less than 10-3. However, this is harder to analyse as contamination
does not follow a clear statistical distribution. Potential contamination sources are not
randomly distributed.
statistical limitations
It can miss contamination if only a proportion of units
are non-sterile
Facility Design
Water
Categories of Water
Equipment (1)
Equipment (2)
Equipment Sterilization and handling
Personnel
Training - personnel appropriately trained for sterile processing,
including assessment and documentation:
Basic GMP
Fundamentals of microbiology
Personal hygiene, health and cleanliness
Behaviour and aseptic working techniques
Gowning and entry procedures
Cleaning and disinfection
Sterilization procedures, validation and routine operation
Emergency procedures to protect product quality (e.g. loss of HVAC System, loss of
power, equipment interventions etc.)
Gowning
Personnel must correctly wear appropriate clean room garments
Detailed, easily understood, gowning procedure (preferably illustrated)
Aseptic Techniques
Personnel in the aseptic manufacturing area, must understand the
principles of aseptic procedures
They must only be considered qualified after appropriate training,
working under supervision and demonstration of competence
The supervisor should observe technique & correct as necessary
All personnel directly involved in aseptic processing must participate in
a media fill at least once per year
Glove disinfection
Sterile disinfectants must be available (e.g., alcohol based)
Glove disinfection must be reasonably frequent, defined in SOP.
Monitoring Plan
Terminal Sterilization
Steam Sterilization
Lower antimicrobial efficacy than moist heat, thus higher temperatures and/or longer
Steam Sterilization
Principle:
Contaminating organisms are not killed, but are retained on the filters. Any faults in
Validation includes:
Routine Filtration
reuse of filters.
Manufacturing Environment
Thank You
Any Questions