Professional Documents
Culture Documents
Presented by:
Efrat Hartog-David
Regulatory Affairs, Qsite
Introduction
Sterilization
Process used to transform product free from viable
microorganisms
Microorganisms
Bacteria
Viruses
Fungi
Introduction
Why
y sterilization is needed?
Medical device is
assembled in
controlled
t ll d
environment,
but mayy contain
microorganisms
Introduction
Why
y sterilization is needed?
Sterilization purpose
p p
Inactivation of microorganisms
D value:
Time required to
achieve inactivation of
90% of a population of
the microorganism
under specific
f conditions
Sterility
Probability of a
viable organism
being present
on a product unit
after sterilization
SAL of 10-6 is required
byy the FDA for
invasive medical
device
Sterilization methods
Moist heat
Gamma radiation
ETO sterilization
Chemicallyy reactive
Irritating,
g, carcinogenic,
g , mutagenic
g g
gas
Alkylation
y reaction cause damage
g to DNA and
proteins of microorganisms
ETO sterilization
Preconditioning/conditioning
Exposure
p to relative humidity
y and temperature
p
Ensure uniformity of conditions
Sterilization cycle
Exposure to ETO gas
g
Aeration
Dissipation of remaining gases
ETO sterilization
Process parameters
Gas quantity
>400mg/L
Temperature
p
~45C
Relative humidity
~35 80%
Exposure time
~90 360 minutes
ETO sterilization
Advantages
Most product and packaging materials are compatible
Relatively low temperature process
Disadvantages
Penetration sometimes difficult
Residuals
Long process and release time
Gamma radiation sterilization
Gamma radiation
Brittle
Color
Odor
Stiffness
Softens
Toxicity
Chemical inertness
Melt temperature
Gamma radiation sterilization
Advantages
Deep penetration power
No residuals
Only one process parameter time
p
Low temperature p
process
Release immediately after sterilization
Disadvantage
Not all product and packaging materials are
compatible
Sterility concerns
Sterilization validation
Objectives
j
Applicable
pp standards
ANSI/AAMI/ISO 11135-1:2007
Sterilization of health care products Ethylene oxide -
Part 1: Requirements for the development, validation and
routine control of a sterilization process for medical
devices
ANSI/AAMI/ISO 11135-2:2008
Sterilization of health care products Ethylene oxide -
Part 2: Guidance on the application of ISO 11135-1
ETO sterilization validation
IQ
Q - Installation Q
Qualification
IQ shall demonstrate that the sterilization equipment
have been installed in accordance with their
specification
OQ Operational Qualification
OQ shall demonstrate that the installed equipment is
capable of delivering the specified process within
defined tolerances
ETO sterilization validation
Product definition
Product families
Product configuration
Product and ppackaging
g g materials
Density
Manufacturingg environment
Bioburden
PQ - Performance Qualification
PQQ Physical
y
Physical PQ shall confirm the predetermined process
parameters throughout the load, for the duration of the
sterilization process
PQ - Microbiological
Microbiological PQ shall confirm the effectiveness of
the defined process in achieving the required SAL, for
product/load combination
ETO sterilization validation
PQ - Physical
PQ Microbiological
PQ Microbiological
Bioburden estimation
Bioburden estimation
Validation Cycles
Fractional cycle
3 x Half cycles
y
Full cycle
ETO sterilization validation
Biological Indicators (BI)
BI product
Full cycle
y
O
One
e full
u cyc
cycle
e is
s required
equ ed
Revalidation
Inspection of:
Bioburden
Product design and packaging
Process equipment and parameters
ANSI/AAMI/ISO 11137-1:2006
Sterilization of health care products Radiation - Part 1:
Requirements for development,
development validation and routine
control of a sterilization process for medical devices
ANSI/AAMI/ISO 11137-2:2006
Sterilization of health care products Radiation - Part 2:
Establishing the sterilization dose
ANSI/AAMI/ISO 11137-3:2006
11137 3 2006
Sterilization of health care products Radiation - Part 3:
Guidance on dosimetric aspects
p
Gamma radiation sterilization validation
Equipment characterization
IQ (Installation Qualification)
OQ (Operational Qualification)
Product definition
Process definition
PQ (Performance Qualification)
Documentation
Dose audit
Gamma radiation sterilization validation
P d t definition
Product d fi iti
Product
P d t families
f ili
Bioburden
Size of product
No. of components
Complexity of product
Manufacturing environment
Gamma radiation sterilization validation
Process definition
A sterilization
t ili ti d dose iis selected
l t d and
d substantiated
b t ti t d
Gamma radiation sterilization validation
PQ
VDMAX25 method
Average
A bi b d shall
bioburden h ll b
be 1000
IInterpretation
t t ti off results
lt
1 non-sterile 25 kGy is substantiated
=22 non-sterile
t il confirmatory
fi t experiment
i t
>2 non-sterile sterilizaion dose shall be
re established
re-established
Gamma radiation sterilization validation
Confirmatory
Co ato y verification
e cat o dose e experiment
pe e t
Select 10 products from a single batch
Irradiate at verification dose (10%)
Product sterility test
Interpretation of results
All sterile 25 kGy is substantiated
>1 non-sterile sterilizaion dose shall be
re established
re-established
Gamma radiation sterilization validation
VDMAX25 method dose audit
Determine average
g bioburden
Interpretation of results
Interpretation of results
All sterile 25 kGy is substantiated
1,
1 4 non-sterile augmentation of the sterilization
dose
5
5 non
non-sterile
sterile sterilization dose shall be
re-established
Sterilization validation additional tests
Product functionality
Packaging integrity
Visual inspection
Peel test
Dye penetration test
Sterilization validation
M i t i i process effectiveness
Maintaining ff ti
A
Assessment
t off change
h
A change
h tto equipment,
i t product,
d t packaging,
k i or lloading
di
pattern