Sterilization

Question 1

Sterilization and sterility definitions

Answer 1

Sterilization- complete elimination of micro-organisms including bacterial spores (not prions)
Sterility- the absence of viable micro-organisms

Question 2

Sterilization overview

Answer 2

Sterilization is an essential stage in the processing of products for parenteral administration, contact with broken skin, mucosal surfaces or internal organs, and the sterilization of microbiological materials, soiled dressings and other contaminated items

Question 3

Terminal sterilization

Answer 3

Product is sterilized in its final container wherever possible
Wherever possible, appropriate additional treatment applied e.g. heating of the product in its final container
In all cases, the container and closure are required to maintain the sterility of the product throughout its shelf life
If terminal sterilization is not possible, filtration through a bacteria- retentive filter (aseptic processing) is used

Question 4

BP methods of sterilization

Answer 4

Moist heat (steam sterilization)
Dry heat
Gamma or electron radiation
Ethylene oxide gas
Filtration
Other methods can be used if they are appropriately validated

Question 5

Physical, chemical and removal processes

Answer 5

Physical processes- elevated temperature (moist and dry heat), irradiation (gamma rays, high energy electrons)
Chemical processes- the application of a biocidal agent (glutaraldehyde, peracetic acid), reactive gas (ethylene oxide, LTSF, chlorine dioxide), gas plasma
Microbial removal processes- filtration

Question 6

Choice of sterilization methods

Answer 6

Level of microbial contamination (bioburden)
Properties of the product to be sterilised: aqueous, oily solutions, emulsions, or dry powder device- metal, plastic, combination of materials, natural e.g. cotton or synthetic materials
Effect of method on product (physical, chemical)
Effect of method on product container/package (physical, chemical)
A suitable process has to be selected to ensure maximum microbial kill/removal with minimum product deterioration

Question 7

Sterility assurance level

Answer 7

Inactivation of micro-organisms by any sterilization process follows an exponential law
There is always a finite possibility of one living cell surviving
The probability of microbial survival is determined by: the number, type, resistance properties and environmental conditions existing within the sterilizing process

Question 8

SAL definition

Answer 8

SAL is the degree of assurance for a sterilizing process to render a population of products sterile
Determination of the probability of a non-sterile item being present within the product population

Question 9

Moist heat disinfection

Answer 9

Moist heat disinfection: temperature below 100c
Pasteurisation: 63c/~30 min; 71c/15s
Tyndallisation- intermittent heating

Question 10

Moist heat sterilization

Answer 10

Temperature of 100c and above
Steaming
Steam under pressure (autoclaving); to attain high temperatures
Ultra-high temperature (UHT) 140c/4 s
The most reliable and widely used means of sterilisation

Question 11

Moist heat sterilization- mechanisms of lethality

Answer 11

Antimicrobial activity- multiple effects
Denaturation of structural and functional proteins, nucleic acids and lipids
Coagulation of proteins and other components to cause cell death

Question 12

Moist heat sterilization process

Answer 12

A three part process:
Heating up stage- articles to be treated are raised to appropriate sterilization temperature
Holding stage- sterilization process
Cooling down stage
Heating up and cooling down stages may contribute to the overall biocidal potential of the process

Question 13

Drying or cooling stages

Answer 13

Dressings packs and other porous loads may become dampened and must be dried before removal from the chamber
Achieved by steam exhaust and application of a vacuum
After drying, atmospheric pressure within the chamber is restored by admission of sterile filtered air

Question 14

Parametric release

Answer 14

The declaration that a product is sterile, based on records demonstrating that the process parameters were delivered within specified tolerances
The decision to release a load of processed devices is based on the results of physical measurements
Do not have to demonstrate that the product is sterile but that the physical parameters have been met

Question 15

Dry saturated steam

Answer 15

Moist heat sterilization requires that steam must be dry and saturated
Saturated- steam is holding as much water as possible in the form of transparent vapour
Dry- it does not contain water droplets

Question 16

Liquid and surfaces

Answer 16

Liquid- raise temperature of liquids within product containers to selected sterilization temperature
Surfaces- 80% of heat energy of steam is released in the form of latent heat when it contacts a cooler surface, this results in steam condensation and contraction, heat and moisture are imparted rapidly to articles being sterilized, dry porous loads are quickly penetrated by the steam

Question 17

Superheated steam

Answer 17

Results from increase in temperature of dry saturated steam without increase in pressure, or from reduction of pressure at constant temperature
Degree of saturation of steam reduces, heat transfer will be similar to dry heat i.e. less effective sterilant
Transient superheating can be tolerated (max. acceptable level of 5c)

Question 18

Wet steam

Answer 18

Results from decrease in temperature of dry saturated steam without decrease in pressure, of from increase at constant temperature
Dry products e.g. dressings become wetted/soaked preventing good penetration of steam into porous material

Question 19

Moist heat sterilization problems

Answer 19

Air removal- important to remove air from the chamber because it impedes the penetration of steam
Steam purity- water contaminants can be carried over in steam and deposited onto the products- toxic effects and damage, determined by the quality of water
Cannot destroy bacterial endotoxins

Question 20

Dry heat sterilization overview

Answer 20

Applications (quite limited in practice) restricted to powders, glassware, metal surgical instruments, non-aqueous thermostable liquids
Industrial application- sterilization of glass bottles filled aseptically
Destroys bacterial endotoxins

Question 21

Dry heat sterilization methods of lethality

Answer 21

Lethal effects of dry heat are due largely to oxidative processes
Higher temperatures and longer periods are needed than for moist heat
Air is a less efficient conductor of heat than steam
Design- hot air oven, infrared conveyor oven, depyrogenation tunnels

Question 22

Dry heat sterilization process

Answer 22

Dry heat sterilisation usually employs temperatures in the range 160-180c and requires exposure times of up to 2 hours depending upon the temperature employed

Question 23

Dry heat sterilization advantages and disadvantages

Answer 23

Advantages: less expensive than moist heat sterilization, useful for moisture sensitive items, no corrosion, useful depyrogenation method (destruction of endotoxin)
Disadvantages: higher temperatures/longer cycle times