Sterilization 3

Question 1

Sterilization parameters

Answer 1

Predict the lethality of the process: inactivation kinetic, predict changes in temperature on the overall lethality, validate alternative regimens (different products)
Examples: D-value, Z-value, inactivation factor, most probable effective dose

Question 2

D-value

Answer 2

Decimal reduction time- resistance of an organism to a sterilizing process
Defined as the time taken at a fixed temperature (or the radiation dose) required to achieve a 90% reduction in viable cells
When reported in the process documentation (e.g. D121), then exposure time is linked at a temperature of 121c

Question 3

Calculation of D-value

Answer 3

Assumes a linear type A survivor curve (first order kinetics)

Question 4

Z-value

Answer 4

Represents the increase in temperature or radiation dose needed to reduce the D-value of an organism by 90% i.e. number of degrees to reduce D-value to 1/10th

Question 5

Calculation of Z-value

Answer 5

The calculation of Z-value assumes a linear type A survivor curve (first order kinetics)

Question 6

Inactivation factor

Answer 6

Reduction in the number of micro-organisms brought about by a defined sterilization process
where IF= 10^t/D
D= D-value for the micro-organism under the defined sterilizing conditions
t=time of exposure under the same conditions or dose

Question 7

Most Probable Effective Dose

Answer 7

The IF calculations are only justified if the survivor curves for a process are linear over the entire exposure time range
Food industry introduced the MPED value
Process dose to achieve n decimal reductions in the number of micro-organisms (independent of the slope of the survivor curve for the process)

Question 8

Sterilization efficiency

Answer 8

Time and temperature relationships- used as proof of acceptable/satisfactory sterilization conditions
e.g. F-value, lethality factor (Fi), lethality coefficient (L), integrated lethality

Question 9

Why validate?

Answer 9

The sterility of a product cannot be guaranteed by testing, it has to be assured by the application of a suitable validated production process.
It is essential that the effect of the chosen sterilization procedure on the product is investigated to ensure effectiveness and the integrity of the product and that the procedure is validated before being applied in practice

Question 10

Validation

Answer 10

Documented procedure for obtaining, recording and interpreting data required to show that a process will consistently comply with pre-determined specifications
Two types of data required for any sterilization process: commissioning data, performance qualification data

Question 11

Commissioning data

Answer 11

Evidence that process equipment has been installed in accordance with specifications
Equipment is safe to use
Functions within pre-determined limits

Question 12

Performance qualification

Answer 12

Evidence that equipment will produce a product with an acceptable assurance of sterility
Physical and biological evidence
Must be re-evaluated if any changes are made to the product, its packaging, its loading pattern or the sterilization cycle
International governing bodies release details on sterilization validation

Question 13

Physical performance qualification

Answer 13

Evidence that the specified sterilizing conditions have been met within the final product (including packaging), throughout the sterilizing cycle
Data generated from worst spot in sterilizer
Tests dependent upon sterilizing method
Data must be generated to show that the sterilizing process has no deleterious effect on the product and its packaging

Question 14

Routine sterilization monitoring- physical monitors

Answer 14

measurement of heat distribution by thermocouple, pressure variation by gauges or transducers, and relative humidity by hygrometers or direct calorimetry
Sensors must be maintained and calibrated regularly

Question 15

Routine sterilization monitoring- chemical indicators

Answer 15

Use of chemical substance which undergoes chemical and or physical change during the sterilizing process
Different types of indicators available: process, single variable, multi-variable, integrating and specific
Indicator performance may be altered by storage conditions before and after use, and by method of use
One single end point reaction, used only to show whether product has undergone a sterilizing process, not that the process was satisfactory

Question 16

Single variable indicators

Answer 16

Graduated response or defined end point reaction
Indicator of one critical variable within process
Types include Temptubes- glass tubes containing chemical with specific melting point indicated by a colour change

Question 17

Multi-variable indicators

Answer 17

Indicator of two or more critical variables within process types include ‘Browne’s tubes’- produce a colour change when specific time at temperature scenario has been achieved

Question 18

Integrating indicators

Answer 18

Quantitative indicators of a combination of critical variables within process
Examples are the liquid or solid dosimeters used to indicate radiation sterilization
Dose-related change from colourless to red

Question 19

Specific indicators

Answer 19

Example Bowie Dick test- a standardised test pack placed in centre of porous load sterilizers
If process correct, uniform colour change occurs across the test package
If air in system, steam fails to penetrate correctly, this observed as a non-uniform colour change in package

Question 20

Biological performance qualification

Answer 20

Evidence that specified sterilizing conditions deliver the require microbiological lethality to product
Obtained from data from the inactivation of reference micro-organisms
Reference organisms introduced to sterilizing cycle in carrier vehicle or inoculated directly into/on the product
Data not required if the sterilizing process conditions well-defined

Question 21

Biological indicators

Answer 21

Measure the effect of the sterilizing process, as a whole, directly
Non-pathogenic
Above-average resistance to a particular sterilization process
Not recommended for routine use (except for gaseous sterilization)
Recommendations for the use of BIs can be found in official documents, such as the BP, EN and ISO publications

Question 22

Good manufacturing process

Answer 22

Precautions necessary to minimise the pre-sterilization bioburden include the use of components with an acceptable low degree of microbial contamination
Qualified personnel with appropriate training
Adequate premises
Suitable production equipment, designed for easy cleaning and sterilization
Adequate precautions to minimise the bioburden prior to sterilization