AAMI ENote

ABOUT AAMI
The Association for the Advancement of Medical Instrumentation (AAMI) is a nonprofit

organization founded in 1967. It is a diverse community of nearly 7,000 professionals united by
one important mission— the development, management, and use of safe and effective
healthcare technology.
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biomedical engineers and technicians, physicians, nurses, hospital administrators, educators,
scientists, manufacturers, distributors, government regulators, and others with an interest in
healthcare technology. AAMI fulfills its mission through:
• Courses, conferences, and continuing education, including certification programs.

• Collaborative initiatives, including summits with the FDA
• A rich array of resources, including peer-reviewed journals, technical documents, books,
videos, podcasts, and other products.
The Association for the Advancement of Medical Instrumentation (AAMI) has granted
permission to the program speakers to quote from standards produced and published by AAMI.
Views expressed by the speakers herein do not represent the views of AAMI or any AAMI
Standards Committee or U.S. Technical Advisory Group administered by AAMI. Information
concerning the content of draft standards that speakers may include within these materials is
subject to change as a result of ballot and public review. Therefore, the content of a final
standard could differ significantly from the content of its draft version.
AAMI is a not-for-profit association whose programs include the development of voluntary

consensus standards for medical devices, and educational programs about medical devices for
the healthcare community. AAMI does not test or otherwise evaluate specific products or
services, endorse specific products or services, or attempt to monitor claims by manufacturers
or consumers that certain products or services meet, or do not meet, AAMI standards.
Published by the
Association for the Advancement of Medical Instrumentation
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Arlington, VA 22203-1633
Phone 703-525-4890
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Copyright © 2012 by the Association for the Advancement of Medical Instrumentation excluding
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All Rights Reserved.
No part of this publication may be reproduced in any form, in an electronic retrieval system or
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Printed in the United States. Updated 3/22/2016.

Click to edit Master title style
Industrial Ethylene Oxide

Sterilization for Medical
Devices
Click to edit
Association forMaster title style of Medical Instrumentation
the Advancement
AAMI is a nonprofit organization of over 7,000 members.

AAMI’s mission is to support the healthcare community in the
development, management, and use of safe and effective
healthcare technology.
AAMI fulfills its mission through:

• Development of industry standards
• Continuing education, conferences
• Certification of healthcare technical specialists
• Publication of technical documents, periodicals, books, software
4301 N. Fairfax Drive, Suite 301 tel. 703-525-4890

Arlington, VA 22203-1633 fax 703-276-0793
www.aami.org
2
Click to edit Master
Administrative Notestitle style
•Emergency contact form

•Breakfast each day – 7:00 am
•Course hours – 8:00 am to 5:00 pm
– Last day 8:00 am to 12:00 pm
•Lunch – 12:00 PM to 1:00 pm
•Breaks in the morning and afternoon
•Cell phones on silent
•WIFI password
•Location of restrooms
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Courseto Materials
edit Master title style
LMS
– eNotebook - PDFs of the PowerPoint lectures
– Appendix with supplemental references
– Industry practices
– AAMI TIR15 2009
– AAMI TIR28 2009
– ISO 11135 Gap Analysis
– Faculty bios
Exercise Workbook
– Daily course evaluations
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AbouttoThis
editCourse
Master title style
Interactive
– Share experiences and ask questions
– Participate by completing daily/overall evaluations
Daily schedule will include
– Lectures
– Situation analysis
– Interactive exercises
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Industrial Master title
Sterilization style
Courses
• Ethylene Oxide Sterilization for Medical Devices

• Radiation Sterilization for Medical Devices
• Industrial Sterilization for Medical Devices
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Certified MasterSterilization
Industrial title style Scientist
Certification
– Demonstrates professional accomplishment, skill mastery, and
experience in core competencies
Key Domains
– Quality Management Systems
– Sterilization Agent, Process, and Equipment Characterizations
– Product and Process Definition
– Validation
– Routine Monitoring, Control and Product Release
– Maintaining Process Effectiveness
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Click to Introductions
Faculty edit Master title style
Faculty for AAMI’s training programs are drawn from an

experienced group of professionals from the medical device
industry, academia, and FDA.
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Click to edit
Attendee PollMaster title style
Type of Organization
Your Job Title/Function
Years of experience with EO Sterilization
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Click to editExpectations
Workshop Master title style
Be an active participant
Questions
– Ask questions
– Parking lot
Please be prompt
– Morning, breaks & lunch
Please, NO cell phones!
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Click to editGoals
Workshop Master title style
At the end of this workshop, you should be able to:

– Determine if validation, qualification, or requalification is necessary
– Compile reports that can stand alone
– Troubleshoot cycle anomalies
– Make changes (product, equipment, process, and sterilizer
location)
– Evaluate the most appropriate release method for the product
– Improve turn around time (development and routine)
– Optimize the cycle
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Overview of Master
Workshop
title style
Module 1 Validation and Requalification

Module 2 Protocols and Reports
Module 3 Product Release Methods
Module 4 Process Specifications
Module 5 Troubleshooting
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Overview of Master
Workshop
title style
Module 6 Ethylene Oxide Residuals

Module 7 Optimization of Sterilization Process
Module 8 Product Change
Module 9 Process Changes/Equivalence
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1. Validation & Requalification
Module 1 Objectives
At the end of this module, you will be able to:

– Distinguish between validation, performance qualification and
requalification
– Discuss the phases of a sterilization validation
– Identify the requirements for requalification
– Discuss the considerations for determining when and how to
requalify the process
– Given a scenario, give recommendations for what requalification
runs, if any, should be performed
– Given a scenario and the requalification decision tree, determine
the extent of the requalification and make appropriate
recommendations with supporting rationale.
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Definition - Validation
3.57 Validation
Documented procedure for obtaining,
recording and interpreting the results required
to establish that a process will consistently
yield product complying with
predetermined specifications.
ANSI/AAMI/ISO 11135:2014
Phases of Validation
Validation
Installation Operational Performance

Qualification Qualification Qualification
(IQ) (OQ) (PQ)
Responsibilities When Using Contract Sterilizer
IQ OQ PQ
• Contractor • Contractor • Contractor

conducts conducts conducts in
conjunction with
• Manufacturer • Manufacturer Manufacturer
ensures • Ensures
requirements met requirements • Manufacturer
are met • Establishes
• Reviews/Audits requirements
prior to PQ • Ensures
requirements
are met
Installation Qualification (IQ)
•Equipment
– Sterilization equipment
– Ancillary equipment
•When Conducted
– Primarily done only after the initial installation of the equipment
– May need to be repeated or a portion repeated following
equipment changes or revisions
– Mostly consists of documenting that the equipment is installed per
specification
Installation Qualification (IQ)
•Operating procedures
– Instructions for operation
– Fault conditions
– Calibration and maintenance
– Technical Support
•Location of equipment
•Health & Safety
•Drawings
Operational Qualification (OQ)
•Make sure all equipment calibrated prior to OQ

•Demonstrates that the installed equipment is capable of
delivering the specified process within the defined
tolerances.
•Can be carried out in either
– Empty chamber
– Loaded chamber would be in combination with the PQ
Performance Qualification (PQ)
•Performed in the equipment to be used to sterilize the

product
– Must be performed in the production chamber.
•Demonstrates
– Equipment consistently delivers the process
– Process produces sterile product
•Uses a
– Representative or worse case load
– Defined loading pattern
Validation

(IQ) (OQ) (PQ)
Microbiological
Physical PQ
PQ
Prerequisites for Microbiological PQ (MPQ)
Comparative resistance or sub-lethal

– Includes natural product bioburden
– Appropriateness of
• Biological indicator (BI)
• Process Challenge Device (PCD)
• External PCD
Biological Indicators (BI)
•Test system containing

viable microorganisms
providing a defined
resistance to a specified
sterilization process
•For EO the viable

microorganism is Bacillus
atrophaeus
Microbiological PQ (MPQ)
•Demonstrates that the sterilization process meets

the requirements for sterility
– BI/Bioburden approach
– Overkill approach
•Performed in the production chamber
•Process parameters deliver less lethality than the
routine sterilization process
– One or more process variables can be reduced or
below the minimum levels specified for routine control
BI/Bioburden Approach
Annex A of ANSI/AAMI/ISO 11135

Process Lethality Determination
– Direct Enumeration
• Typically 4 runs
– Fraction Negative
• Holcomb-Spearman Karber (HSK)
– Typically 5 runs
• Stumbo Murphy Cochran (SMC)
– Typically 3 runs
Overkill Approach
Annex B of ANSI/AAMI/ISO
11135
Half cycle
– Three runs
– Total kill in all 3 runs
Cycle calculation
– Based on data from lethality
determination (Annex A)
– 12 log reduction
SAL
1.E+06 Curve
1.E+04
1.E+02
1.E+00
Half Cycle
Time 0 MPQ Time CC Exp. HC Exp.
Cycle Calculation
1.E-02 Time Time
1.E-04
1.E-06
1.E-08
Validation

(IQ) (OQ) (PQ)
Microbiological
Physical PQ
PQ
Physical PQ
Demonstrates reproducibility of the process

– At least three runs
– Can use MPQ cycles to satisfy part of the requirement
(at least one full cycle PPQ must be run)
Specified acceptance criteria are met throughout the

load for the duration of the proposed routine
process specification
Physical PQ
9.4.3.2 PPQ shall confirm the process such that:

a) the minimum temperature of product to enter the sterilization
process and/or the defined conditions required to achieve it shall
be established;
b) at the end of the defined preconditioning time (if used), the
sterilization load temperature and humidity have been
established;
c) the specified maximum elapsed time between the completion of
preconditioning (if used) and the commencement of the
sterilization cycle is appropriate;
Physical PQ

d) at the end of the defined conditioning time, if used, the
sterilization load temperature and humidity have been
established;
e) the chamber humidity was recorded if parametric release was to
be used;
f) gaseous EO has been admitted to the sterilizer chamber;
g) pressure rise and the quantity of EO used or concentration of
EO in the sterilizer chamber have been established. If parametric
release is to be used, the value and tolerances of EO
concentration;
Physical PQ

h) during the sterilization cycle, the temperature and humidity (if
recorded) of the chamber and, where applicable, other process
parameters have been established;
i) the temperature of the product load during exposure has been
established;
j) during aeration (if used), the temperature of the sterilization load
has been established.
Maintaining Process Effectiveness
12.2
12.3
Maintenance of
Requalificaiton
Equipment
12.5 12.4
Assessment of Assessment of
equivalence change
Maintaining Process Effectiveness
•Calibration of equipment
•Maintenance of equipment
•Periodic requalification
•Evaluation of changes
Definition - Requalification
3.37 requalification
Repetition of part of validation for the
purpose of confirming the continued
acceptability of a specified process
Overall Goal of Requalification
12.2
12.3
•Demonstrate the sterilization
Requalificaiton
process remains valid

Maintenance
of Equipment
12.5
Assessment of
equivalence
12.4
Assessment of
change
•Annual review to determine extent
of requalification:
– Equipment
– Product
– Processing History
• Meets regulatory requirements
• Meets business needs of cost effectiveness
and timeliness
Requirements for Requalification
Requalification shall verify

– Reviewed annually to determine extent of requalification
• SAL is achieved
• BI/PCD is still appropriate
• Load & loading pattern are still appropriate
• Product still meets requirements and/or specifications
• Documented
– Any sterilization process determined as not capable
• Investigated
• Corrective and/or preventive action taken
• Documented
– Records retained
Determine Extent of Requalification
Figure D.1 – Requalification decision tree

Annual Review – Review of IQ
Annual
Review D.12.3.1 – ANSI/AAMI/ISO
11135:2014
(IQ) (OQ) (PQ)
• Control and monitoring
equipment show no calibration
issues
• No significant changes found:
• Change control process
• PM program
Annual Review – Review of OQ
Annual
Review
D.12.3.2 - ANSI/AAMI/ISO 11135:2014

Installation
Qualification
(IQ)
Operational
Qualification
(OQ)
Performance
Qualification
(PQ)
• Original OQ confirmed as still valid
• Periodic requalification of equipment:

• Review of IQ status
• Assessment of trends in equipment performance
• No significant changes since previous (re)qualification
• Temperature and RH profiles in preconditioning areas
• Chamber temperature profile
• Temperature profile of aeration areas
• If equipment changes are necessary, then requalification
of equipment might be needed
Annual Review – Review of PQ
Annual
Review D.12.3.3 - ANSI/AAMI/ISO 11135:2014
• Sterilization process remains valid for
(IQ) (OQ) (PQ)
designated product(s)
• Review of IQ & OQ equipment
• Confirmation
• No significant changes in product or process
• No significant increase in population or resistance in product
bioburden
• Processed functioned as specified since last qualification
• No changes to process that could impact sterility
• Review of BI/PCD failures while process specifications were still met
Extent of Requalification
Full • Conduct PPQ

Qualification • Conduct MPQ
• One Fractional/Half Cycle including load

Reduced temperature & humidity measurements
Requalification • If requalifying production chamber, use
production chamber for study
Documented • Document justification

Rationale • Until next review
Additional Requalification Recommendations
•Verify paper review every two years by performing

– MPQ cycle
– Load Temperature
– Humidity measurements
•Confirm EO residuals as specified in
ANSI/AAMI/ISO 10993-7:2008/(R)2012
Establishing Requalification Program Considerations
Multiple locations
– If process equivalence has been established, then not
required to requalify every vessel
Multiple cycles
– Each would need to be requalified
Different product mix
Example
•Annual Review
– Two chambers validated at sterilization facility X.
– Process equivalence was used to qualify the 2nd
chamber.
– Only one sterilization process is used for a product
family consisting of three products.
• Annual assessment of each chamber, the process, and all
products.
• Requalification is performed biennially and the chambers are
alternated so that a requalification is performed once in 4 years
for each chamber.
•Requalification Option
Situational Analysis
Annual Review
• Read the situation
• Work in small groups
• Using the Requalification Decision Tree,
answer the questions
1. Which of the 3 requalification options would be
most appropriate: Full Qualification, Reduced
Requalification, or No run (Document
Rationale)? Give your rationale for your decision.
2. Based on the assessment, should any
microbiological or physical qualification runs be
performed? If so, what do you recommend?
Provide a rationale for your decision.
Target Responses – Module 1 Situational Analysis
Annual Review
1. Which of the 3 requalification options would be most

appropriate: Full Qualification, Reduced MPQ/PPQ, or No
physical/microbiological qualification? Give your rationale
for your decision.
Reduced MPQ/PPQ - A Full Qualification would not be required
since not all aspects affecting the MPQ and PPQ are impacted
by the changes. Because the overall bioburden level of the product
did not change, but there were indications that there was an
increase in fungi (which might be due to Pyronema because the
cotton was from China) then some microbiological qualification
should be performed.
Annual Review
2. Based on the requirements for requalification, what are

your recommendations for this situation? Provide your
rationale.
–The microbiological requalification should consist of a sub-
lethal cycle to ensure the increased fungal count of the product
has not caused an increase in resistance that would invalidate the
PCD.
–Also, because the temperature sensor in the preconditioning

room was low on calibration it might be recommended to review
the data from the room to demonstrate that there were no
instances where the room was out of specification – if this had not
been done by the sterilizer.
Documentation
•Document all assessments

•Document all rationales for decisions
•Defined plan for future reviews
Example – Annual Assessment Documentation
Annual EO Assessment #1
Section 5.3 Sterilization Process & Equipment Assessment

• Sterilization process – unchanged
• Sterilization equipment – IQ and OQ addressed
• Process Challenge Device – unchanged
Retrieve
Document
Example – Annual Assessment Documentation
Annual EO Assessment #1
Section 5.4 Product & Process Assessment

• Product Bioburden
• Product Design
• Manufacturing Process or Components/Materials
• Manufacturing Environment
• Packaging
Writing Conclusions
•Address any acceptance criteria

•Be clear
•Provide the rationale
•State what the conclusion means for the process,
i.e. it’s:
– Validated
– Qualified
– Requalified
Case Study
Writing Conclusion for Annual Assessment for

Requalification of AAMI Product 2
Instructions
• Review the Annual Assessment for AAMI
Product 2
– Group 1 – Read Section 4.0
– Group 2 – Read Section 5.0
– Group 3 – Read Section 5.0 + 6.0
• Write the section of the conclusion as assigned
to your group. Be prepared to provide rationale.
– Group 1 – Write Section 7.1
Target Responses – Module 1 Case Study – Group 1
Writing Conclusion for Product 2 Annual Assessment

7.1 AAMI Product 2 Design, Materials, Packaging, &
Manufacturing Process
7.1.1 There were no significant design or material changes
made to the product that were not approved through the
change control process. However following the addition of the
heparin a subsequent evaluation of product residuals was not
performed. Changes to the packaging were not adequately
addressed during testing and it is unclear if the porosity change
was advantageous to the sterilization process either from a
lethality or residual perspective. The bioburden of the product has
increased. Since the time of the packaging change and increase
in bioburden, an evaluation of the natural product bioburden as
related to the PCD has not been conducted.

7.2 Sterilization Process & Equipment
7.2.1 The sterilization process change was adequately
addressed through change control and found to be
acceptable. The process has performed consistently since the
last requalification. However the change in the PCD was only
approved in the Biological Indicator Evaluator Resistometer (BIER)
Vessel and the performance of the PCD was not addressed in the
production vessel. The equipment changes have been approved
but there has been an overall shift in the temperature range of the
vessel since the original PQ. In addition the requalification
performed in 2006 did not have the appropriate number of
temperature sensors.
7.3 Suppliers
7.3.1 The suppliers used for laboratory and sterilization
services were found to be acceptable. However it should be
noted that the sterilization contractor did not inform the company
when it was found that the temperature sensor was out of
calibration.
Target Responses – Module 1 Case Study
Writing Conclusion for Product 2 Annual

Assessment
7.4 Overall Conclusion
Based on the above assessment the conclusion
is that requalification is required. At a minimum
the following should be performed:
7.4.1 A sub-lethal cycle to confirm that the resistance
of the natural product bioburden has not increased
to a point to invalidate the use of the PCD.
7.4 Overall Conclusion

7.4.2 A half cycle to confirm that the new PCD
configuration demonstrates adequate kill in the half cycle.
7.4.3 A full cycle to confirm the product residual levels

remain compliant with ANSI/AAMI/ISO 10993-
7:2008/(R)2012.
Summary
• Sterilization validation consists of Installation

Qualification, Operational Qualification, and
Performance Qualification including Physical PQ
and Microbiological PQ
• Requalification is repetition of a portion of a
validation confirming the continued acceptability
• Assessment for Validation/Requalification
• Determines the recommendation for
validation/requalification
• Must be documented
2. Protocols & Reports
Module 2 Objectives

–Identify components of a good protocol
–Discuss best practices for writing acceptance criteria
–Given acceptance criteria, evaluate its quality and appropriateness
within a protocol
–Identify report requirements and qualities of a good report
–Discuss deviations and appropriate actions for addressing deviations
–Evaluate the report to identify strengths and weaknesses
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Why is it important?
9.5.1 The purpose of this activity is to

undertake and document a review of the
validation data to confirm the
acceptability against the approved
validation procedures/protocol for the
sterilization process and to approve the
process specification.
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• Why is it important?
The standard requires documented evidence
• Subject to considerable scrutiny
• FDA
• Notified Bodies
• Other Regulators
• Customers
• Lawyers
4 AAMI University
Components of a Good Protocol
Clear purpose, scope, or objective
Rationale or basis documented
References defined
Equipment, materials specified
Detailed procedures/instructions
Meaningful acceptance criteria
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Designed to Answer Questions
Clear purpose, scope, or objective
• What kind of study is to be performed

– Validation (IQ, OQ, and PQ)
– Qualification (IQ, OQ, or PQ)
– Requalification (Part of the IQ, OQ, or PQ)
– Adoption and Process Equivalence
• Why the study is to be performed? (Purpose)
• What the study encompasses (Scope)
• The ultimate goal (Objective)
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Protocol Purpose Example 1
Purpose
The purpose of the protocol is to outline the sterilization validation
activity for qualifying the Ethylene Oxide (EO) process for AAMI Inc.
medical devices, which results in a minimum sterility assurance level
(SAL) of 10-6.
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Protocol Purpose Example 2
Purpose
The purpose of this protocol is to document the requirements for the
qualification of the 100% Ethylene Oxide (EO) sterilization process for
AAMI Corporation (AAMI) medical devices, which results in a
minimum sterility assurance level (SAL) of 10-6. This protocol is
based on practices recommended by the American National
Standards Institute/ Association for the Advancement of Medical
Instrumentation/ International Organization for Standardization.
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Protocol Purpose Example 2, cont.
(ANSI/AAMI/ISO) 11135:2014, Sterilization of health care

products – Ethylene oxide – Requirements for the
development, validation and routine control of a sterilization
process for medical devices.
The successful completion of this protocol will:

• Demonstrate the efficacy and reproducibility of the
sterilization chamber and its ancillary equipment along
with demonstrating the lethality of the sterilization process.
9 AAMI University
The successful completion of this protocol will:

• Provide documented evidence that the sterilization
process will deliver a minimum six log reduction of the
microbial challenge at one-half the exposure dwell time.
Therefore, the full exposure dwell time will provide a
sterility assurance level (SAL) of at least 10-6.
10 AAMI University
•Demonstrates that the internal process challenge device

(IPCD) is a greater challenge to the EO process than the
naturally occurring bioburden.
•Demonstrates that EO residual levels are acceptable
following multiple cycle exposures.
•Completes the qualification of the sterilization sub-contractor
as an approved supplier for AAMI.
•Establishes a validated Sterilization Cycle for commercial
product distribution.
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Protocol – Scope Example
This document describes the Ethylene Oxide (EO)

Sterilization Validation Protocol for the AAMI Medical Device.
The sterilization validation will include the following

evaluations:
• Process Definition
• Appropriateness of BI/IPCD
• Appropriateness of the external PCD
• Acceptance of sterility test system
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
– Microbiological
– Physical
12 AAMI University
Protocol – Scope Example, cont.
•The EO sterilization process that pertains to this validation

protocol will be performed by BugKiller Sterilization located
at 5450 Micro Lane, Death Valley, CA. Chamber No. 6 will
be the sterilization vessel, which has a 7 pallet capacity
(740.9 ft3), and the cycle number will be documented in the
accompanying Test Report.
•The test laboratory that will perform all pertinent

microbiological and chemical analysis will be Gro-It
Laboratories located at 1008 Pasteur Avenue, Jackpot, NV.
Iris @ BugKiller to make final recommendation on Chamber
and Cycle
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Protocol Examples
Rationale or basis documented
•May be a section by itself or part of another section such as

“Background”
•Should document any prior testing that provides background
to the study
•Provides the reasoning for the study, makes it specific
•Expands on the purpose/objective
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Evaluating Objectives & Scope

Retrieve
Document
Instructions
• Use Protocol Example 1 – AAMI University -
Industry Practices
• Evaluate Objective and Scope Sections of
Protocol Example 1
– List 3 strengths
– List 3 weaknesses
15 AAMI University
Evaluating Objectives & Scope
• Strengths
– Method is defined
– Establishes an EO validation
– Specifies sterilization facility/company
• Weaknesses
– The product to be validated is not clearly specified
– The ultimate goal is not clear
– Information is included in the scope is really beyond the scope
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Protocol - Improvement Examples
References defined
Protocol Example 3 Improvements

• A list of documents related to the protocol
• Standards (ISO, FDA, etc.)
• Guidance documents (AAMI TIRs, etc.)
• Previous studies (Validations, Qualifications, Engineering studies,
Requalifications)
• Internal procedures
Retrieve
Document
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Protocol – Improvement Examples
Equipment, materials specified
Protocol Example 4 Improvements

• Specifically identify the equipment to be used
• Specify biological indicators, type, and population
• Clearly document the placement of the BI in the product and
how the PCD is made
• Define dunnage and provide justification
• Tables can be a good way to document what items are included
in each run
•BIs, Sensors, Product/Package Samples
Retrieve
Retrieve
Document
Document
18 AAMI University
Protocol Writing Tips for Procedures/Instructions
Detailed procedures/instructions
Do Don’t
• Make them easy to • Make them so detailed and
understand specific that they cannot be
• Use pictures or drawings followed without deviation
• Specify front & back
• Document parameters in the
same format/units as the
sterilizer
19 AAMI University
Protocol – Defining Critical/Non-Critical Parameters
Meaningful acceptance criteria
Items that MUST BE met for the protocol to be successful

– For example, all IPCDs in the half cycle must exhibit no growth of
the indicator microorganism
Define critical process parameters such as:
– Critical parameters may include:
• Temperature
• Pressure
• Time
– Non-critical process parameters would not compromise intent of
cycle
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Protocol – Writing Acceptance Criteria
•Section that specifies the criteria

•Write the criteria with flexibility when appropriate
•Don’t include specific ranges if it is NOT required for
process
– Temperature limitations
– Humidity limitations
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Acceptance Criteria Examples
•Example
– The sub-lethal cycle must be performed according to the cycle
parameters as defined in Attachment 2.
•Improvement of Example
– All sub-lethal cycles must be performed according to the cycle
parameters as defined in Attachment 2, or any deviations
determined not to impact the intent of the cycle.
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Evaluating & Revising Acceptance Criteria

Instructions
• Review the following acceptance criteria
• Evaluate the acceptance criteria & decide if each item
should:
• Remain the same,
• Be revised, or
• Excluded.
• Be prepared to give your rationale.
• Rewrite the criterion, as necessary
23 AAMI University
1. Revised
– 1.0 All process parameters shall be within the limits established
in this protocol. Any parameter deviations must not impact the
intent of the cycle to be accepted.
2. Revised
– 2.0 All Internal Process Challenge Devices subjected to a half cycle
process or full cycle process must be negative for growth. At least 46 of
50 IPCDs shall be tested.
24 AAMI University
3. Revised
– 3.0 Product test of sterility samples must be negative for growth in the
fractional cycle.
4. Revised
– 4.0 Biological Indicator Population - The minimum
(verified/stated) population for use in this protocol is 1.0 × 106.
– (Note that the ISO and USP requirements use a tolerance from the
stated population to confirm acceptance)
25 AAMI University
5. Same (No Change)

– 5.0 At least one positive control of each BI lot utilized must
be tested with each spored cycle to be used for this study. Each
positive control must yield growth of the indicator.
6. Same (No change, if included, but it might not be

necessary especially in an initial PQ.)
– 6.0 Humidity Injection - The calculated percent relative
humidity shall be equal to or greater than 29% for the half cycles
(minimum percent relative humidity is based upon the tolerances
specified for the chamber temperature and amount of humidity
injection).
26 AAMI University
7. Exclude (Since the word “should” is used this is not a

true acceptance criteria and therefore not be included.)
–7.0 The temperature spread across the load by completion of the
exposure should be ≤ ± 9°F as measured by the mean of all
functional temperature sensors.
8. Revised
–8.0 The EO and ECH levels in the product must conform to the
limits established in ANSI/AAMI/ISO 10993-7:2008/(R)2012 for a
(limited/prolonged/permanent) exposure device.
–(It would be advisable to include a table of the limits especially if
more than one exposure time has to be met.)
27 AAMI University
Documentation
Processing records
Sample and sensor placement verification
Preconditioning charts/printouts
Sterilization cycle printouts
Temperature/Humidity sensor reports
Aeration charts/printouts
Lab reports
28 AAMI University
Cycle Data Analysis Example
Protocol 395 Cycle Data 395
Compare the data to the

protocol requirements of 8.2
Sub-lethal Cycle on p. 4
Retrieve
Document Look at the data in
sub-lethal cycle
29 AAMI University
Temperature and Humidity Data Example
Protocol 395 – p. 17 PDF Sensor Placement Record

p. 3 PDF
Review sensor placements

30 AAMI University
Temperature and Humidity Data Example
Protocol 395 – p. 18 PDF Sensor Records starting

on p. 13 PDF
Review product temperature

31 AAMI University and humidity data
Comparing Preconditioning Parameters to Data
Preconditioning Range Actual

Parameter
Room 90º - 120ºF 110º - 112ºF
Temperature (From PC Chart, page 8 of PDF)
Room Humidity 50 – 80% 49 – 65%

(From PC Chart, page 8 of PDF)
Time 12 h 12 h
Minimum (From Load Record, page 2 of PDF)
32 AAMI University
33
Comparing Sterilization Parameters to Data
Sterilization Range Actual

Parameter (From Run Record)
Initial Evac 2.0 +/- 0.5” HgA 2.0” HgA, page 4 of PDF
Humidity Inject 3.0 +/- 0.5” HgA 3.2” HgA

Humidity Dwell 30 – 0, +15 min. 30 min., page 5 of PDF
Gas Inject 16.0 +/- 0.5” HgA 16.0” HgA, pg 5

Gas Dwell 15 – 5, +0 min. 15 min., page 6 of PDF
34 AAMI University
35
Importance of the Report
Once the validation is completed the only thing that is left is

the report
This is a historical document that needs to stand by itself as

it is the only explanation for:
– Criteria Selection
– Decisions/Rationale
– Selected Processes
36 AAMI University
The Report
9.5.3 A validation report shall be prepared.

The report shall be reviewed and approved
by the designated responsible person(s).
(see items listed in ANSI/AAMI/ISO 11135:2014)
37 AAMI University
The Report
9.5.4 The validation report shall describe or

reference the specific qualified product,
the defined load configurations and the
documented specifications for the EO
sterilization process and shall address:
(see items listed in ANSI/AAMI/ISO 11135:2014)
38 AAMI University
Qualities of a Good Report
 Documents all of the requirements of the protocol

 Addresses all the deviations with appropriate rationale
including acceptance of deviations
Summarizes the results of the study in the report
References where raw data is located
Documents that acceptance criteria were met
Includes an Overall Conclusion
39 AAMI University
Report - Documentation of Protocol Requirements
Example Protocol Report Documentation

requirement states Example
– One sub-lethal cycle, – A sub-lethal cycle, three
three half cycles and half cycles, and three full
three full cycles will be cycles were performed
performed. as specified in the
protocol.
Should be clear & informative
40 AAMI University
Documentation of Protocol Requirements
Example of Improved – Report Documentation
The cycles as defined in the protocol were successfully

performed as follows:
– A sub-lethal cycle (Run #07-18-002) was performed on 7/18/08.
The cycle data is summarized in Table 2 and the run records are
included in Annex 5.
– The half cycle runs were performed on 8/4/08 (Run #08-04-003),
8/11/08 (Run#08-11-001), and 8/18/08 (Run #08-18-002). The
cycle data is summarized in Table 3 and the run records are
included in Annexes 6, 7, and 8.
– The full cycle runs were performed on 8/25/08 (Run #08-25-003),
8/28/08 (Run#08-28-001), and 8/31/08 (Run #08-31-002). The
cycle data is summarized in Table 4 and the run records are
included in Annexes 9, 10, and 11.
41 AAMI University
Table 2: Sub-lethal Cycle Summary
Table 2: Sub-lethal Cycle Summary
PRECONDITIONING Specification Range Run #14067
Minimum Product Temperature, °F N/A 76.4
Time, hours 8 - 12 10.68
Temperature, °F 80 - 120 109 – 111
Relative Humidity, % 40 – 75 63 – 70
Transfer time, minutes 60 – 90 8.4
Load Temperature at PCR End, °F N/A 107.5 – 110.0
Load Humidity at PCR End, %RH N/A 49.5 – 56.9
Specification Range Run #14067
STERILIZATION CYCLE Chamber 7
Process Temperature, °F 115 - 135 122 - 126

Vacuum A, inHgA 1.5 - 2.5 2.0
Approximate Rate, ” Hg/ minute 1.0 0.9
Leak Test, in Hg 0.0 - 0.3 0.2
Leak Test Hold Time, minutes ≥10 10
Nitrogen Dilution Pressure, inHgA 23.5 - 24.5 24.0
Approximate Rate, ” Hg/minute 1.0 1.0
Nitrogen Dilution Evacuation, inHgA 1.5 - 2.5 2.0
Number of Dilution Cycles 1 1
Humidification (Pressure Rise), inHg 1.0 - 2.0 1.5
Humidity Dwell, minutes 50 - 90 60
Pressure Maintained At, inHgA 3.0 – 4.0 3.3 – 3.7
Steam Additions N/A 3 steam additions
Load Temperature at End of Humidity Dwell, °F ≥104 109.9 – 118.8

Load Humidity at End of Humidity Dwell, %RH ≥30 57.6 – 67.2
Gas A, EO Pressure, inHgA 12.0 – 13.0 12.5
Gas Weight, lbs N/A 38
Gas Dwell Temperature, °F 120 - 130 125 – 126
Load Temperature at Start of Gas Dwell, °F ≥109 116.1 – 124.1
Gas Dwell Time, minutes 55 - 65 60
Maintain Pressure w/ Sterilant, inHgA 12.0 – 13.0 12.4 – 12.5
After Vacuum, inHgA 1.5 - 2.5 2.0
Gas Wash (Nitrogen) Pressure, inHgA 14.5 – 15.5 15.0, 15.0
Approximate Rate, ” Hg/ minute 1.0 1.1, 1.1
Gas Wash Evacuation, inHgA 1.5 - 2.5 2.0, 2.0
Number of Wash Cycles 2 2
Gas Wash (Air) Pressure, inHgA 14.5 – 15.5 15.0, 15.0
Gas Wash Evacuation, inHgA 1.5 - 2.5 2.0, 2.0
Number of Wash Cycles 2 2
Release, inHgA 24.8 - ATM 24.8
AERATION Specification Range Run #14067
Cell 1 – 12 12
Temperature, °F 80 - 120 102 – 110
Time (for the load), hours ≥24 24.55
Load Temperature throughout aeration, °F N/A 84.8 – 113.4
42 AAMI University
Report – Addressing Acceptance Criteria
•Usually in a separate section of the report but could be

addressed throughout the body of the report
•Restate the acceptance criterion from the protocol
– Can be restated exactly with demonstration of how it was met
specified underneath
– Restate but in a way that just demonstrates the criterion was met
43 AAMI University
Report Example – Addressing Acceptance Criteria
Protocol acceptance Report states:

criteria states: Following 18 hours of
The total EO content of the heated aeration the EO
Catheter must be no more content of the Catheter
than 4 mg and the ECH was less than 0.25 mg with
level no more than 9 mg at a TCL of 4 µg/cm2. The
the day of release. In ECH level was 0.08 mg
addition the tolerable with a TCL of 0.001
contact level (TCL) must µg/cm2. The EO and ECH
not exceed 10 µg/cm2 for levels meet acceptable
EO and 5 mg/cm2 for ECH. levels prior to the release
of the product for use.
44 AAMI University
Report Example – Addressing Deviations
Protocol requirement Report results states:

states: The product and RH
The product temperature sensors were programmed
and RH sensors will be to read at a 6 minute
programmed to record 5- interval rather than the 5
minute intervals. minute interval specified in
the protocol, see section
4.2 for a discussion of this
deviation.
45 AAMI University
Report Example – Addressing Acceptable Deviations
4.2 Deviations:
4.2.1 The product temperature and RH sensors used
in the sub-lethal cycle were programmed to record
every 6 minutes rather than the protocol requirement
of 5 minutes. This requirement is to ensure that
readings are taken frequently throughout the
sterilization process. The additional minute between
readings is not significant and does not impact the
acceptance of the validation.
46 AAMI University
Deviation in Cycle Data 395a

Retrieve
Situation
Document
• The sub-lethal cycle was run on 12/4/07. The product
test of sterility samples were not placed until 12/17/07.
• Protocol states 8.2.5 “The sterility samples will be placed
with the positive PCD controls into a shipping carton that
contains ice packs. These samples will be sent to
Laboratory using the next day air service. Laboratory
will conduct the testing per the product specification
within four hours of receiving the samples.”
Questions
• Would it be advisable to accept this deviation?
• Give rationale for decision.
47 AAMI University
Deviation in Cycle Data 395a
• Would it be advisable to accept this deviation?

• Give rationale for decision.
–No, In this case the run should be rejected and not accepted on
deviation because the time between the cycle and testing was so long
(13 days).
48 AAMI University
Report Example – Addressing Unacceptable Deviations
3.0 Deviations to the Protocol:

3.1 The product was not tested within 4 hours of
receipt by the laboratory, is was tested after 13 days. There
was no growth observed in any of the product samples;
however, because this was a sub-lethal cycle where growth
could be anticipated it cannot be determined if the lack of
growth was due to the extended time between sterilization
and testing or the cycle itself. Therefore this deviation is
unacceptable and the sub-lethal cycle will be repeated.
49 AAMI University
Report – Overall Conclusion
•May be a single statement or several statements

•Includes identification of
– Process
– Product
– Location (facility and chamber)
– Specifics
•Confirms successful validation, qualification, or
requalification
50 AAMI University
Example – One Statement
Overall Conclusion
The 100% EO sterilization process (Cycle #24) for the AAMI Device in
the load configuration defined in the protocol has been successfully
validated at BugKiller Sterilization Facility in Chamber #3 achieving
the required SAL of 10-6 or better. The routine sterilization process is
defined in Attachment 4.
51 AAMI University
Closer Look – Report 1 Example
Retrieve
Document
52 AAMI University
Report 1 Example
Strengths:
1. Documents all of the requirements of the protocol in the results
section
2. Addresses all the deviations with appropriate rationale including
the acceptance of the deviations in section 3.0
3. Summarizes the results of the study in the report
• See 2.1.1, Tables 1 - 4
4. References where raw data is located
• See 2.2.1
5. Documents that acceptance criteria were met (in the conclusions
section)
Weaknesses:
• Does not include an overall conclusion although the summary may
serve as an overall conclusion
53 AAMI University
Summary
Documentation represents the activities, evaluation, and

rationale for confirming the validity of the sterilization
process.
Acceptance criteria
– Only include items in the protocol that are required for
a successful acceptance of validation
Common errors:
– Protocol requirements/acceptance criteria poorly written
– Documentation is not thoroughly reviewed
– Report fails to stand alone and thoroughly document the validation,
qualification, or requalification
54 AAMI University
3. Product Release Methods
Module 3 Objectives

–Compare conventional release to parametric release
–Explain the considerations for selecting the release method
–Given a situation, determine the most appropriate release method
Product Release Methods
Conventional Release Parametric Release

• Verify parameters • Based only on specific
• Test BIs/PCDs to parameters
ensure cycle meet the • Gas concentration
requirements • Chamber temperature
• Chamber humidity
Parametric Release
10.5 If parametric release is performed, the following

additional data shall be recorded and retained:
a) temperature in the chamber from a minimum of two
locations throughout the sterilization cycle;
b) chamber humidity during conditioning as determined by
direct measurement;
c) the EO concentration, determined from direct analysis of
chamber atmosphere at defined intervals sufficient to verify
the required conditions throughout the exposure time.
Routine Monitoring For Parametric Release
No special Microbiological PQ method is

Microbiological
PQ required
• Only chamber temperature must be
monitored routinely
• Only chamber humidity must be
monitored routinely
• Gas concentration must be monitored
routinely
Considerations During PQ
Performance • Variations in loads/products should be

Qualification
(PQ) evaluated during the qualification process.
– Maximum and minimum loading
– Most dense and least dense
– Differences in the levels of absorptive material
• Nitrogen injection after EO injection will affect
the gas concentration profile.
• Determine when to monitor and specification
– Start of EO Dwell, greater than value
– End of EO Dwell, less than value
– Other times
Nitrogen Injection
With Nitrogen Blanket

600
500 N
i
400 t
r
300 o EO Concentration
g
200 e
n
100
0
16:23 16:28 16:33 16:38 16:39 16:54 16:59 17:04 17:09 17:14 17:19 17:24 17:29 17:34 17:39 17:44 17:49 17:54
Decline in EO Gas Concentration
Starts at End of EO Injection
End of Exposure
Parametric Release – Equipment Considerations
Is the equipment capable?

Equipment
Capable? • Can the EO gas concentration be
monitored?
Product • Can the humidity be monitored directly
Candidate?
during conditioning?
• Can the temperature be recorded from
Timeliness?
2 locations?
Cost/Benefit?
Parametric
Release
Parametric Release – Product Considerations
Is the product a candidate?

Equipment
Capable? • Does the product aerate in less time
than:
Product • Incubation time for BI?
Candidate?
• Shipping BIs to lab for testing?
• Is the load consistent?
Timeliness?
• Uniform loads are easier and less costly to
qualify and establish the gas concentration
Cost/Benefit?
requirements.
Parametric
Release
Parametric Release – Time/Testing Considerations
Will the release time truly improve?

Equipment
Capable?
• Are there post-sterilization testing
that is time consuming?
Product
• i.e. LAL, package testing, product
Candidate? functionality
Timeliness?
Cost/Benefit?
Parametric
Release
Parametric Release – Cost/Benefit Considerations
Is there a cost benefit?

Equipment
Capable?
• Additional costs from:
• Contractor?
• Validation work?
Product
Candidate?
• Annual microbiological PQ?
• Savings
• Time?
Timeliness? • Reduction of inventory?
Are there quality questions?
Cost/Benefit?
• Non-conformances
• Specific process
• General to sterilization facility
Parametric
Release
Case Study
Product Release Selection

Instructions
• Work in assigned groups
• Sterilization Processes for
• Product A – IV Catheter
• Product B – Intra Ocular Lens
• Product C – Blood Oxygenator
• Determine most appropriate release method
• Conventional or Parametric Release
• Give rationale for determination
Product A – IV Catheter
Which release method would be most appropriate?

Why?
• Parametric release would be the best choice:
• Since 6 days could be eliminated from the release time,
• There are ongoing cost savings, and
• The one-time costs of installation/qualification of the equipment
are significantly less than the one-time savings for inventory
reduction.
Product B – Intra Ocular Lens

Why?
• It is a toss up because
• There is not really a significant reduction in the release time.
• The ongoing cost savings favors parametric, but the one-time
savings is small.
Product C – Blood Oxygenator

Why?
• Conventional release would probably remain the most
appropriate since:
• There is no release time savings.
• The ongoing costs are higher.
• There are one-time charges with no off-setting savings.
Summary
Selecting the best release methods is dependent

upon several factors:
• Equipment
– Performance of process
• Product
– Load configuration
• Time
• Cost/Benefit
4. Process Specifications
Module 4 Objectives

–Develop a process specification
–Determine if a process meets the specifications
–Given cycle data and process specifications, determine if the cycle is
compliant
2 AAMI University
Routine Process Speicfications
9.5.6 A process specification including the

process parameters and their tolerances shall be
established for routine processing based upon the
documentation generated during the validation.
This process specification shall also include the
criteria for designating EO processed product as
conforming product and approved for release.
3 AAMI University
Routine Monitoring and Control
10.1 The purpose of routine monitoring and control is

to demonstrate that the validated and specified
sterilization process has been delivered to the
product.
4 AAMI University
Routine Process Specifications
a) the minimum temperature of product entering the sterilization

process and/or the defined conditions used to acclimate the
load;
b) temperature and humidity within the preconditioning area,
monitored and recorded from a specified position;
c) time of commencement of preconditioning and of removal of
load from preconditioning of each sterilization load;
d) elapsed time between removal of the sterilization load from
preconditioning and the commencement of the sterilization cycle;
Note that a) is required even if preconditioning is not used.

5 AAMI University
e) chamber humidity during conditioning and/or humidity dwell

phases by pressure, pressure rise (ΔP) and/or direct monitoring;
f) conditioning time;
g) indication of the satisfactory operation of the chamber gas
circulation system (if used) during EO injection and during
exposure;
h) temperature and pressure in the chamber throughout the
sterilization cycle;
6 AAMI University
i) If pressure is used as the primary control measure, the

requirement for the secondary measure is only to confirm
admission of EO to the chamber by at least one of the following:
1) the mass of EO used;
2) the direct measurement of the concentration of EO in the sterilizer chamber;
3) volume of EO used;
j) EO-injection time
k) inert gas injection, if used;
l) exposure time;
m) time taken to evacuate the chamber;
n) time and pressure changes during post-exposure flushing;
o) time, temperature, pressure changes (if any) during aeration.
7 AAMI University
Critical Parameters – Conventional Release
• Initial vacuum level

• Evacuation time
• Inert gas addition pressure (if used)
• Humidity inject pressure
• Humidification time
• EO gas addition pressure
• EO gas exposure time
• Chamber temperature
• After exposure evacuation pressure
• Inert gas or air pulse pressures
• Exposure times at vacuum or pressure
8 AAMI University
Critical Parameters
Aeration, if used
• Time
• Temperature
• Pressure changes (if any)
Test Results
• BI, if used
• Other product related testing as required
9 AAMI University
Critical Parameters – Parametric Release
Same as Conventional Release plus

a) Temperature in the chamber from a minimum of two locations
throughout the sterilization cycle;
b) Chamber humidity during conditioning as determined by direct
measurement;
c) The EO concentration, determined from direct analysis of
chamber atmosphere using analytical methods at defined
intervals sufficient to verify the required conditions throughout the
exposure time.
10 AAMI University
Parameter Set-points & Tolerances
Determined by the capability of the equipment.

Generally specified by the Contractor for items such as
– Temperature in chamber
– Rates for evacuations and pressurizations
– Vacuum level
– Leak Tests
11 AAMI University
Case Study
Develop a Process Specification

Instructions
• Work in assigned groups.
• Use the following documents
• Case Study – Develop a Process Specification
• Develop the routine process specification for the product.
Retrieve
Document
12 AAMI University
Case Study
Evaluate a Run
Instructions
• Use the following documents:
– Target Responses – Develop a Process Specification
– Case Study Evaluate a Run
– Cycle Data #1
• Compare Cycle Data to Cycle Specification
– Write in the run data into the chart.
• Is the run compliant? Why or why not?
Retrieve
Document
13 AAMI University
Summary
The process specification provides instructions to the

sterilizer on how to process the product.
The process data must be reviewed against the specification

to determine acceptance.
14 AAMI University
5. Troubleshooting
Module 5 Objectives

–Categorize critical and non-critical non-conformities during routine
EO processing
–Investigate and report the results of a failure investigation
–Assess and determine the appropriate actions:
•If parameters/specifications are not achieved during sterilization
•For BI failures or misplacement of BIs
–Given a scenario, assess and determine appropriate actions for a
failure investigation
Troubleshooting/Routine Process
A non-conformity or an out-of-specification (OOS) condition

occurs with a routine process
– Includes both below or above specification
– Includes all phases of the process
Determine the Criticality
Critical Non-Critical
–Any non-conformity –Other non-
that has the potential conformities
to impact the –An action other than
lethality/residual of the reprocessing can be
process taken
–Results in the
reprocessing of the
load
–Additional aeration of
the load
Non-Conformities & Recommended Actions
Troubleshooting Guide
Retrieve – Preconditioning
Document
– In Chamber Process
• Through EO Exposure
• Post EO Exposure
– Aeration
– Biological Indicator (BI) or Process Challenge
Device (PCD) Issues
Non-Conformities
Instructions:
Using the Troubleshooting Guide, categorize the following non-
conformities as either critical or non-critical and explain your
rationale.
1. Positive BI growth reported as Micrococcus luteus
2. EO injection specification is 389 – 423 mBar and the

cycle printout shows 382 mBar.
3. Initial evacuation pressure specification is 1.5 – 2.5

inHgA, cycle is at 1.4 inHgA.
4. One chamber temperature sensor fails during cycle.
Non-Conformities
5. Exposure time specification is 5.5 – 6 hours, cycle

printout shows 370 minutes due to a power failure.
6. EO Preconditioning temperature room specification is

37 - 49°C. Duration is 24 – 48 hours, chart show that
for 30 minutes the temperature was 35-36°C.
7. Concentration (direct measurement) specification is

560 – 750 mg/L throughout exposure. For 15 minutes
the EO concentration was below 560 and dropped as
low at 545 mg/L.
Non-Conformities
1. Positive BI growth reported as Micrococcus luteus

– Non-critical since the indicator organism was not found and the
positive is considered a contaminant.
2. EO injection specification is 389 – 423 mBar and the

cycle printout shows 382 mBar .
– Critical since the minimum pressure, i.e., gas concentration,
wasn’t met.
– However, if there were other anomalies then it would be non-
critical if the minimum concentration was achieved.
Non-Conformities
3. Initial evacuation pressure specification is 1.5 – 2.5

inHgA, cycle is at 1.4 inHgA.
– Non-critical if there are no product or package related effects.
4. One chamber temperature sensor fails during cycle.

– Critical if this is the only recording sensor or if it is a parametric
cycle there are not another 2 sensors.
5. Exposure time specification is 5.5 – 6 hours, actual time

was 370 minutes due to a power failure.
– Non-critical, but should perform residual analysis.
Non-Conformities
6. Preconditioning temperature room specification is 37 -

48°C. Duration is 24 – 48 hours, chart show that for 30
minutes the temperature was 35-36°C.
– Critical if not found until data review because the minimum
preconditioning time is not met,
– Non-critical if found before end of preconditioning and can add
the time or if during the validation a lower time was validated but
not used for the specification.
Non-Conformities
7. EO concentration (direct measurement) specification is

560 – 750 mg/L throughout exposure. For 15 minutes the
EO concentration was below 560 and dropped as low at
545 mg/L.
– Critical because concentration is below specified value for
lethality.
Process Non-Conformities
11.2 If a process does not fulfil all of the

conformance criteria above, the cause shall be
investigated. If repair or alteration to the equipment
is required, the necessary qualification shall be
performed before this process can be used again.
Failure Investigations
Instructions
– Work in small groups referring to the situations on
slides 6 & 7.
– Conduct a failure investigation answering the following
questions.
Questions
1. What is the possible cause of the failure?
2. Based on the possible cause, is the non-
conformity likely to reoccur?
3. What type of qualification (Full IQ, OQ or PQ or
partial IQ, OQ, PQ) should be performed, if any?
Give rationale for your decision.
Situation #1 Positive BI Growth Reported as
Micrococcus luteus
– Usually the cause is a testing issue at the lab or in rarer cases it could
indicate a packaging issue.
2. Based on the possible cause, is the non-conformity likely to reoccur?
– Not usually frequently but if it does a lab change may need to be
considered.
3. What type of qualification (Full IQ, OQ or PQ or partial IQ, OQ or PQ)
should be performed, if any? Give rationale for your decision.
– None, because the issue does not affect the integrity
of the qualification data.
Situation #2 Low EO Injection Pressure

– This might be due to an equipment malfunction, aging, or possibly a
power outage.
2. Based on the possible cause, is the non-conformity likely to
reoccur?
– Possibly if due to a malfunction or aging.
– Probably not; however, frequent power outages can be handled
preventively with a uninterrupted power supply (UPS).
3. What type of qualification (Full IQ, OQ or PQ or partial IQ, OQ or
PQ) should be performed, if any? Give rationale for your decision.
– Possibly, part of the IQ/OQ if the equipment is replaced
Situation #3 Initial Evacuation
Pressure Below Specification
– Generally equipment related.

– Not typically.

– None, since the issue does not affect the integrity of the qualification
data.
Situation #4 One Chamber
Temperature Sensor Fails
– Equipment related.

– Not typically.

– None, because the issue does not affect the integrity of the qualification
data.
Situation #5 Exposure Time Above Specification
– Storms, accidents, brownouts, blackouts, power surges.

– Not if the power outage was not related to a common occurrence, but if it
is expected or happens frequently a UPS should be considered.

– None, because the issue does not affect the integrity of the qualification
data.
Situation #6 Preconditioning
Temperature Below Specification
– Causes include equipment malfunctions, power outages, door openings

– No for power outages, but if it happens because of door openings, it
should be assessed if the number was typical or greater than usual.
Possibly if the equipment needs to be replaced.

– None if due to malfunctions or power outages but if the door openings or
other situations will be ongoing then a MPQ might be necessary. Possibly
a portion of the IQ/OQ if equipment is replaced.
Situation #7 Low EO Exposure

– It could be equipment related i.e. sensor out of calibration, sensor drift. It
could be product related certain loads can absorb more EO result in a
lower concentration in the chamber space.

– It might if the sensor is not holding up in the process and needs to be
calibrated more frequently or a different sensor used. If it is load related
then it could also occur when that load combination is used.
Situation #7 Low EO Exposure
– For the equipment, if it is a calibration issue then no qualification. If the
sensor needs to be replaced or a different type used then some IQ/OQ is
needed.
– If it is a load issue, then PQ will be needed to ensure that the extremes of
loading are addressed or an adjustment of parameters is made which
might result in PQ runs being required.
BI Failure Investigation – Items to Address
• Does the BI meet requirements?

• Were there changes to BI presentation?
• Was the lab testing compliant?
• Was the load as validated?
• Were there changes in climate conditions?
• Were there changes in product/package (internal
BI/PCD)?
• Did the cycle parameters – including pre-conditioning –
meet the specification?
EO Concentration Formula
How to Calculate EO Concentrations

Retrieve
Document
C = (K x P)/(R x T)
Where
C = Concentration (mg/L)
K = Constant for Sterilant (4.4 x 104 for 100% EO)
P = Pressure differential
R = Gas constant (0.08205 atm l/gm moles K)
T = Absolute temperature in K
(convert from oC by adding 273 to temperature
oC = (oF – 32) x 5/9)
Humidity Calculation Formula
Steam Tables
Retrieve
Document
%RH = [(Pt – Pi)/Pss] x 100
Where
Pt = Pressure at the end of steam injection
Pi = Initial evacuation pressure
Pss = Saturated steam pressure at Tdc
(from steam table, ASME 1983)
Tdc = Temperature at the end of steam injection
Case Study
Failure Investigation
Instructions
–Read the situation and data.in Failure Investigation Case Study
–Work in assigned groups.
Helpful Resources
– AAMI University - Industry Practices Folder
• Troubleshooting Guide
• How to Calculate EO Concentrations eNotebook Reference Folder
• Failure Investigation Steam Tables
Retrieve
Document
Case Study
Situation
– A BI failure occurs in a routine cycle in January.
– Use the Case Study Failure Investigation
Answer the questions:

1. What was a probable cause of the failure?
2. Is this non-conformity likely to reoccur? Why or why not?
3. What type of qualification (Full IQ, OQ or PQ or partial IQ, OQ,
PQ) should be performed, if any? Give rationale for your
decision.
4. What actions should be taken?
1. What was a probable cause of the failure?

– In this investigation based on the information presented the only
anomaly was that the transfer time from preconditioning was
greater than what had been validated. Since the load was
processed in January it would be probable that the load cooled too
much and the external PCD was affected, resulting in the positive.
2. Is this non-conformity likely to reoccur? Why or why
not?
– It is not likely to reoccur since it was due to an operator error.
3. What type of qualification (Full IQ, OQ or PQ or

partial IQ, OQ or PQ) should be performed, if any?
Give rationale for your decision.
– None would be required unless for some reason the facility cannot
meet the 60 minute transfer limit routinely.
4. What actions should be taken?

– Actions to be taken would include retraining of the operators on the
specification, eliminating any thing that may have prevented the
transfer, and potentially requalification if necessary.
Summary
• Critical non-conformities require reprocessing

• Conduct failure investigation and document
results
–Assess and determine the appropriate actions:
• If parameters/specifications are not achieved during
sterilization
• For BI failures or misplacement of BI
6. Ethylene Oxide Residuals
Module 6 Objectives

– Identify the properties and health hazards of the three
EO residuals from the EO sterilization process
– Discuss the residual limits established in standard
ANSI/AAMI/ISO 10993-7:2008/(R)2012
– Given a device, determine the extent of testing and the
applicable limit for EO residuals
– Apply dissipation curve analysis to aeration times
Ethylene Oxide Residues
The amount of residue depends on

– Materials
• Composition
• Absorptive characteristics
– EO concentration
• Higher concentration usually yields higher residual level
– Contact time
• Longer gas dwell time usually yields higher residual levels until
steady state occurs
– Product Design
– Packaging
EO Residual Analysis
Product Selection
– Each product
– Product families
• Test the worst case
– Worst case may be different for EO and ECH
– Packaging needs to be considered
– Kits
• Test components that have contact
• Test worst case
EO Residuals
By-products of the EO sterilization process
Ethylene Oxide Ethylene Ethylene Glycol

(EO) - C2H4O Chlorohydrin (EG) - C2H6O2
(ECH) - C2H5ClO
EO Residual Properties
Characteristics EO ECH EG
C2H4O C2H5ClO C2H6O2
Molecular • Simple epoxy Wt. 80.5 Wt. 62.07
• Wt. 44.05
Water Soluble Yes Yes Yes
Volatility Extremely Reactive Stable Stable

• Explosive in air • Must be • Low
at atmospheric heated to high Flammability
pressure temps • Flash point -
• Limit by Volume • Flash point - <116ºC
Flammability • Upper 100% <60ºC (<241ºF)
• Lower 2.6% (<140ºF)
• Flash point –
<-18ºC (<0ºF)
Boiling Point Colorless Gas Colorless Liquid Colorless Liquid
(Atmospheric 10.7 ºC (<51.3ºF) 128 to 130 ºC 197ºC
Pressure)
• EO Residual Properties
2-chloroethanol (ECH) reacts with photochemically
produced hydroxyl radicals in the atmosphere as a result
its half life will be approximately 11.5 days. Reference -
NIH US National Library of Medicine - 2-Chloroethanol
CAS RN:107-07-3
• The vapor pressure of ECH under vacuum is as follows:
@ 1 kPa or 0.3 InHgA the temperature required is 23 deg
C.
• The vapor pressure of ECH under vacuum of 10kPa or
2.95 InHgA is 67.1 deg. C.
• At 2.0 InHgA the minimum temperature required would be
approximately 51.2 deg. C. or 124.2 deg. F
National Fire Protection Association Hazard
Label
Ethylene Oxide Hazards
Health Hazard
– Toxic by inhalation
– Carcinogen
– Reproductive hazard 4
– Blue 3 – Health Hazard-
Extreme Danger
Healthcare Products 3 3
– Physically absorbed into
materials of device
– Essentially dissolved in the
absorptive material
ECH Hazards
Health Hazard
– Toxic by inhalation
– Toxic by skin absorption
– Affects the
2
• Central nervous system
•
•
Cardiovascular system
Kidneys
4 0
• Liver
Healthcare Products
– Formed in the presence of
chloride ions
EG Hazards
Health Hazard
– Skin irritant
– Can be lethal by ingestion –
sweet taste
1
Healthcare Products
– Formed in a reaction with
water (usually acidic)
2 1
Ethylene Oxide Residue Limitations
EO and ECH Limits

– Specified in ANSI/AAMI/ISO 10993-7:2008/(R)2012, Biological
evaluation of medical devices — Part 7: Ethylene oxide
sterilization residuals
– The limits specified in the above standard are Tolerable
Exposures based on a body mass of 70 kg. To Change see
Section G.6.1 Tolerable exposure TE
– The tolerable exposure (TE) is the product of the TI, body mass
(mb), and a utilization factor (UTF): TE = TI × mb × UTF
There are no specified limits for EG
– Certain natural materials (e.g., collagen, cotton, etc.) may result
in extremely high concentrations of EG
– The manufacturer must show this does not present a
hazard to the patient or compromise the performance
of the medical device
EO Residual Limits
For patient contacting devices only
Permanent Prolonged Limited

Contact Exposure Exposure
Avg Daily Dose 0.1 mg/day 2 mg/day 4 mg
1st 24 hours 4 mg 4 mg N/A
1st 30 days 60 mg 60 mg N/A
Lifetime 2.5 g N/A N/A
ECH Residual Limits
For patient contacting devices only
Permanent Prolonged Limited

Contact Exposure Exposure
Avg Daily Dose 0.4 mg/day 2 mg/day 9 mg
1st 24 hours 9 mg 9 mg N/A
1st 30 days 60 mg 60 mg N/A
Lifetime 10 g N/A N/A
Calculation of Average Daily Dose
Type of Exposure Calculation

Limited Exposure Divide by 1 day
Prolonged Exposure Divide by 30 days
Permanent Contact Divide by 25,000 days
What to Test?
Portion of device in contact with the patient directly or

indirectly
– Sterile Fluid Path
– Working end of device
– Entire device
How to Test?
Simulated-Use
– Duplicates the procedure
– Usually <24 hours
Exhaustive Extraction – EO
– Represents a dose ≥ what the patient may receive
– May be multiple extractions over several days (10%)
• Thermal (Headspace)
• Ethanol
• Solvent
• Repetitive water extraction
Tolerable Contact Limits (TCL)
Tolerable Contact Limits Units (TCL)

– EO – micrograms per square centimeter
– ECH – milligrams per square centimeter
Surface Contact or Implanted Devices

– EO – 10 µg/cm2
– ECH – 5 mg/cm2
Note: The unit of square centimeter represents the surface area of

the patient-device interface.
Multi-Device Systems
For multi-device systems the limits shall apply to each

individual patient-contact device.
Special Categories
• Table C.1 Annex C ISO 10993-7

Reference
• Intraocular Lenses
Document
• Blood Cell Separators
• Blood Oxygenators
• Cardiopulmonary Bypass Devices
• Hemodialysers
• Drapes in contact with intact skin
• Multi-component Devices
• Devices for infants/children
Test Scenario – Example
• An ablation device that has a PTFE component and can

not be irradiated
• Does not meet any special category requirements so
standard limits
• Contact is limited since device is used for only a
maximum of 6 hours
• Only the shaft of the device has patient contact during the
procedure
Test Scenario – Example
Considered
alternate
sterilization
methods?
Yes
Is there Yes Yes Do Special No

Only one
patient Categories Determine EO & ECH
device?
contact? apply?
Is patient
EO ≤ 4 mg Is patient Is patient
exposure
ECH ≤ 9 mg exposure exposure
in 24 h
>24h but
Yes <24h? No No >30 days?
≤30 days?
No
Determine EO & ECH

using simulated
extraction
Test Scenario – Example Results
Show the conclusion

– After working though the flow chart.
– Does the example require limit calculation? It would be good if it
did and to show it.
Include the answer to questions
1. Should all, part, or none of the following devices be tested for EO
residuals? Give your rationale.
2. If testing is required should it be simulated-use or exhaustive? Why?
3. What limits apply and does the TCL need to be determined?
EO Residual Testing Analysis

Instructions
• Work in small groups Answer the questions for
• Types of devices each device
1. Should all, part, or none of
A. Absorbable Suture
the following devices be
B. Table Drape tested for EO residuals?
C. Stent Delivery System Give your rationale.
D. Insulin Delivery Device 2. If testing is required should
it be simulated-use or
exhaustive? Why?
3. What limits apply and does
the TCL need to be
determined?

Absorbable Suture
1. Should all, part or none of the following devices be tested for EO
residuals? Give your rationale.
- All of the device because the entire device comes in contact with patient.
2. If testing is required should it be simulated-use or exhaustive? Why?
- Exhaustive because this device is an implant with > 30 day contact
(Permanent Exposure)
- Might require 24 hour testing to determine 24 hour average daily dose
3. What limits apply and does the TCL need to be determined?
- Permanent exposure limits apply
- TCL needs to be determined because the device is an implant
- Might require 24 hour testing to determine the TCL

Table Drape
1. Should all, part, or none of the following devices be
tested for EO residuals? Give your rationale.
– None – testing is not required since there is no patient contact.
2. If testing is required should it be simulated-use or
exhaustive? Why?
– No testing
3. What limits apply and does the TCL need to be
determined?
– No testing

Stent Delivery System
– Part of the device – since only the catheter portion and
potentially any fluid path will have direct or indirect contact
exhaustive? Why?
– Simulated-use testing would be needed since the contact be <24
hours
determined?
– TCL is not required because the delivery system is not a surface-
contacting device nor is it an implant.

Insulin Delivery
– Probably the whole device, but the extraction method might need
to be modified to address only patient contact areas
exhaustive? Why?
– Exhaustive testing would be needed since there is
prolonged/permanent contact
determined?
– TCL is required because the delivery system is a surface-
contacting device
Dissipation Curves
5.3 Dissipation curves are used to estimate the post-

sterilization time required for products, or families of
similar products, to reach residue limits, principally for
EO, in compliance with 4.3. Products shall be
released to the marketplace according to
predetermined post-sterilization times and conditions
defined by experimental dissipation curves so that the
target EO residue levels for the device, as set out in
4.3, are ensured.
ANSI/AAMI/ISO 10993-7:2008/(R)2012
Prediction Limit Formula
Average Release Time
Data vs. Prediction Limit
24h 36h 48h What aeration time would

you use for this limited
6.23 3.46 2.65 exposure device?
6.09 3.91 2.66 –Lp = 39 hours
6.1 3.83 2.21
Resulting in Longer
Aeration Time
Use of Prediction Limit
24h 36h 48h What aeration time would

you use for this limited
1.23 0.72 0.45 exposure device?
1.09 0.71 0.46 –Lp = -26 hours = 0 hours
1.1 0.83 0.41
Resulting in Shorter
Aeration Time
Summary
The EO residuals are EO, ECH, and EG. Each of

these residuals pose serious health hazards to
patients.
– EO & ECH limits have been established in
ANSI/AAMI/ISO 10993-7:2008/(R)2012, Biological
evaluation of medical devices — Part 7: Ethylene oxide
sterilization residuals
– Testing is conducted on the portion of the device that
comes in contact with the patient
– The type of contact determines the type of testing and
limits
7. Optimization of
Sterilization Process
Module 7 Objectives

– Discuss the benefits of optimizing the sterilization process
– Explain strategies for optimizing the sterilization process
– Given a scenario, recommend ways to optimize the sterilization
process
Optimization of Sterilization Process
Possible benefits
– Improved turnaround times
– Reduced cost
– Greater understanding of the sterilization process
Optimization may also include developing the best
sterilization process based on product limitations
– Low temperature processes
– Low humidity processes
– Vacuum sensitive processes
6 Strategies for Optimization
#1 Strategy • Eliminate or Reduce Preconditioning
#2 Strategy • Reduce EO Residuals
#3 Strategy • Reduce Incubation Time for BI
#4 Strategy • Appropriate Selection of PCD
#5 Strategy • Modify Sterilization Cycle
• Eliminate or Reduce Post-Sterile

#6 Strategy Testing
Preconditioning Reduction
#1 Strategy • Eliminate or Reduce Preconditioning
Dependent on location Dependent on product

– Warm vs. cold – Surface sterilization, low
– Product travels bioburden, uniform product
• Short distances, or – Less dense load
• Under controlled conditions – Load configuration allows for
– Sterilization in-house quick heat up
Dependent on cycle
– Dynamic conditioning
3 Types of Conditioning
Pulsed Continuous
Steam Steam
Static Injection
Steam enters Injection Steam entered
(PSI) Vacuum, inert (CSI)
while a vacuum at same rate as
gas, vacuum,
is maintained vacuum creating
steam to set
creating a a curtain of
point
curtain of steam steam
Pull in & push Rapid heat &

out humidification
Caution:
Possible rain on
product
Ways to Reduce or Eliminate Preconditioning
Evaluation of the temperature and humidity profiles

– An analysis may show that the product load meets acceptable
parameters well before the current minimum time
Adjust process parameters
– Increase preconditioning temperature
– Move to dynamic conditioning
– Increase sterilization temperature
Examples – Preconditioning Reduction
Example 1 Example 2
– A load of Catheters – A load of lenses
preconditioned for a – Changed to a 90 minute
minimum of 24 hrs dynamic conditioning phase
– Modified load configuration – Eliminated preconditioning
with a chimney in the pallet
– Reduced preconditioning
time to a minimum of 18 hrs
Ways to Reduce EO Residuals
#2 Strategy • Reduce EO Residuals
Modification to
Sterilization Modification to
Cycle Aeration
Parameters
Modifications to Modification of
the Product or Extraction
Package Method
Reduction of EO Residuals
Modification to
Sterilization
Cycle
Parameters
Reduce EO concentration
Post EO exposure modifications
Reduce EO exposure time
Increase temperature
Modification to
Aeration
Increase temperature
Increase air flow
Increase air exchange rate
Add spacing
Modifications to
the Product or
Package
Change materials
Change product configuration
Change package
Change loading pattern
Examples – Reduction of EO Residuals
Example 1 Example 2
– Running a sterilization cycle – An increase in aeration
at >150ºF temperature by 10ºF and an
– Resulted in releasing increase in the number of
product without aeration air changes
– Reduced the aeration time
from 48 to 24 hours
Modification
Modificationsofto
Extraction
the Product or
Method
Package
Use simulated extraction
methods for devices that are
limited contact.
Test only those portions of the

device that have patient contact.
Complete a Reduced Incubation Time (RIT) Study
#3 Strategy • Reduce Incubation Time for BI
Attachment II of Guidance for Biological Indicators

Industry and FDA Staff for – 4 to 5 days is typical
Biological Indicator (BI) Self-Contained Biological
Premarket Notification (510k) Indicators (SCBI)
Submissions – 2 days is typical
http://www.fda.gov/MedicalDevices
/DeviceRegulationandGuidance/ – 4 hours to 2 days
GuidanceDocuments/ucm071261. Study requirements vary
htm. – FDA
– Notified Bodies
– Production Vessel vs
Research Vessel
RIT Study
Requirements
– Use 3 lots of BIs/SCBIs, 100 BIs/SCBIs per lot
– Cycle parameters identical except exposure time
– Growth must be within 30% to 80% positive at Day 7
– Time when 97% turns positive becomes the minimum time for
incubation
RIT Study Example
Day 3 Day 4 Day 5 Day 6 Day 7

Lot 1 44 45 45 45 45
Lot 2 70 71 72 72 72
Lot 3 65 67 68 68 68
Lot 1 – 97.8% Growth at Day 3

Results: Reduced incubation time is 4 Days
Factors for Selecting External PCD
Determining the appropriate internal challenge for

the product
Product Bioburden
Product Configuration
– If organisms not particularly resistant to sterilization process,
then location of internal PCD not critical
– If several challenge locations are equally difficult, select the
most reasonable location
– Parts of device that have patient contact/access
Factors for Selecting External PCD
Product Configuration
– If the device configuration is not particularly challenging the
where the BI is placed is not critical.
– If several challenge locations are equally difficult, select the
most reasonable location.
– Use product tests of sterility with in comparative tests to
demonstrate EO penetration to areas that are not easily
inoculated with strips/threads.
Example – Breast Biopsy Device
Selection of Inappropriate PCD

– Shaft/trocar introduced into patient
– Device inoculated in several places
• Thread or suspension at a population 106 for internal PCD
• Internal PCD with greatest resistance selected
• Internal PCD selected the external PCD with greater resistance
than the internal PCD
– Result – most resistant of the most resistant
• 10 hour exposure period for product with bioburden
consistently <100 cfu (corrected)
Additional Factors for Selection of PCDs
Consistency of PCD
– PCD manufactured under control
– PCD components documented and changes qualified
Validation method
– Comparative lab studies
– Production chamber results verified
– ANSI/AAMI/ISO 11135:2014 guidance
• Resistance considered equivalent if external is less than but
not more than 20%
Selection of Appropriate PCD

Instructions
• Review the data on the following slide
• Questions
1. Based on the data presented which PCD of
the following PCDs would be most
appropriate for the process? Why?
Data for Selection of Appropriate IPCD

IPCD 1 IPCD 2 IPCD 3 IPCD 4 Product
BI in BI in an BI in a BI in a Results
Product Pouch Double Syringe
Pouch
3/20 3/20 10/20 19/20 0/20
4/20 3/20 6/20 18/20 0/20
2/20 3/20 8/20 15/20 0/20
• Sterility data from 3 research vessel

sub-lethal cycles
• Number positive/Number tested
Selection of Appropriate IPCD
1. Based on the data presented which IPCD of the following

PCDs would be most appropriate for the process? Why?
– IPCD 1 or IPCD 2, due to the greater challenge than the product
but not excessively high resistance
Modification of Sterilization Cycle
#5 Strategy • Modify Sterilization Cycle
Define and qualify the process according to the

product that is sterilized
– It may be possible to shorten the exposure of the cycle
– Many cycles are a lot longer than really needed
because they were set based on a guess, legacy or
whatever worked
Example – Modify Sterilization Process
•A product purchased sterile from a manufacturer with an

existing cycle of 8 hour exposure
•The product was adopted into the current cycle
•When the product is evaluated individually it is discovered

that a fractional cycle of 90 minutes results in no positives
Change the Cycle Definition Approach
Using Overkill Approach

– Reduce the half cycle time by using a time that is more realistic
for the PCD
– Use the cycle calculation approach which only requires an SLR
of 6
Using BI/Bioburden Approach
– Series of runs to set an appropriate cycle time
– Correlate the BI more closely to bioburden than overkill
approach
Using Bioburden Approach
– Bioburden to establish cycle
Cycle Definition Approach Comparison
Overkill BI/Bioburden Bioburden

Simple More complicated Most complicated
Cycle longest Cycle shorter Cycle shortest
(usually)
Bioburden Bioburden Bioburden
not usually more significant most significant
significant
Least expensive More expensive Most expensive
Routine/Valid. Routine/Valid Routine/Valid
Annex B Annex A TIR 16
Example – Cycle Definition Selection
• Sterilization cycle established with overkill method

• Resulted in a cycle with 4-hour exposure
• 5 years of monthly bioburden testing indicate corrected
bioburden of the product does not exceed 20 cfu with less
than 5% spores
• When the cycle is based only on bioburden, a sufficient
exposure time is 1 hour
Other Cycle Adjustments
Increase temperature results in

– Q10 Effect – Thermodynamics
• Every increase of 10oC (18oF) doubles the rate of sterilization
– Greater kill
– Shorter cycle
Increase EO concentration results in
– Greater kill
– Shorter cycle
Post-Sterile Testing Reduction
#6 Strategy • Eliminate or Reduce Post-Sterile

Testing
Testing performed after sterilization process

– Validated for pre-sterile testing such as:
• LAL testing
• Package integrity
• Product functionality
• Other tests
– Reduces time required to release product
Cycle Optimization
Retrieve
Document Instructions
•Using the Case Studies from the Product
Release Module and working in small groups,
answer the following question for each product.
– Product A - IV Catheter
– Product B - Intraocular Lens
– Product C - Blood Oxygenator
•What strategies would you recommend for
optimizing the process for the product? Why?
•Parametric Release is not an option
Cycle Optimization
Product A – IV Catheter
Best options for optimizing the process:

• Reduce preconditioning time or use dynamic conditioning
to eliminate preconditioning
• Qualify a SCBI to replace the existing BI or perform an
RIT study
Cycle Optimization
Product B - Intraocular Lens

• Evaluate cycle modifications, material changes, or
package changes to reduce the aeration time
• If it is possible to reduce the aeration time then other
options such reduction of BI incubation time can be
addressed
Cycle Optimization
Product C - Blood Oxygenator

• Evaluate options to reduce or eliminate preconditioning
• Evaluate cycle modifications, material changes, or
package changes to reduce the aeration time
• If it is possible to reduce the aeration time then other
options such reduction of BI incubation time can be
addressed
• Qualify LAL testing of non-sterile product
Summary
Optimizing processes
– Reduced cost
– Improved turnaround times
– Greater understanding of the sterilization process
The strategies used to optimize a process depends:
– Product, packaging, configuration, materials, bioburden, EO
residuals, and cycle approach
– Evaluation of cycles determine possible optimization
8. Product Change
Module 8 Objectives

– Classify categories of changes for new or modified
product
– Evaluate if the change has an impact on
• Materials and product characteristics
• Configuration, packaging, or load
– Given a change to a product scenario, determine if
validation or requalification is necessary
Definitions - Product Adoption
2.8 Product adoption 2.2 Candidate product
process of formally new or modified product,

including a candidate including the packaging
product into an existing system, proposed for
validated EO processing inclusion in the existing
category or EO product validated sterilization
family process
AAMI TIR28:2016 AAMI TIR28:2016
Product Equivalence
12.5.2 Product
A product may be added to a validated process if deemed
equivalent to or a lesser challenge than an existing qualified
product or internal PCD. A technical review shall be performed
comparing the candidate product with the product or PCD that
was used to validate the existing EO process. The outcome of
the technical review, including the rationale for decisions
reached, shall be documented. The requirements of 7.2 still need
to be addressed for the product.
Assessment of Change Requirements
12.2
Maintenance of
12.3
• Review of changes to assess
Requalificaiton
Equipment
effectiveness of the sterilization
12.5
Assessment of 12.4
process
equivalence Assessment of
change
• Reconfirming appropriateness of
PCD for changes
• Re-evalutate load and load
configurations for changes
Assessment of Equivalence
12.2
Maintenance of
12.3
Determination of
Requalificaiton
Equipment
–Adverse effects to product

12.5
12.4
Assessment of
change
–Product design effects
Assessment of
equivalence
–Product material & characteristics
effects
–Sterile barrier system effects
–Load configuration effects
Benefits of Product Adoption
12.2
Maintenance of
Equipment
12.3
Requalificaiton
• Shorter time in the
development process
12.4
12.5
Assessment of
equivalence
Assessment of
change
• Less costly
• Simplification of the overall
sterilization program
Definitions – Product Family & Processing Category
3.33 Product family 3.31 Processing Category

group of product possessing collection of different product
characteristics that allow or product families that can be
them to be sterilized using sterilized together
defined process conditions Note 1 to entry: All products
within the category have been
ANSI/AAMI/ISO 11135:2014 determined to present an equal
or lesser challenge to the
sterilization process than the
process challenge device for
that group.
Determination of Adverse Effects
Any new or modified product

– Evaluated to ensure that the EO process does not detrimentally
affect the product
• Biocompatibility
– May include residuals and other 10993 testing
• Stability/Functionality
– Shelf life testing of sterile product
– Does the product still function as intended
– Multiple cycles may be required
– Biostability
Categories of Change
Product design (configuration)

Materials and characteristics
– Includes manufacturing location and environment
Sterile barrier system (packaging)
Load
AAMI TIR28:2016, Section 3.3
ANSI/AAMI/ISO 11135:2014, Annex A
Design Evaluation
Is it harder to get gas, humidity, or heat to all parts

of the product when compared to the existing
product or PCD?
– Does the change make product more difficult to
sterilize? or
– Is the new product more difficult to sterilize?
Design Evaluation Considerations
Does the product have more:

1. Restricted passageway or inner chambers?
• Use of more one-way valves, smaller tubing diameter, longer
tubing length, etc.
2. Fewer openings?
• Components that are completely welded rather than spot welded,
not as many open luer connections, etc.
3. Internal surfaces?
• Multi-lumen vs single lumen, more complicated internal
configuration, more items in a tray.
4. Mated surfaces?
• Pressure fittings, threaded fitting, etc.
5. Closures?
• Injection caps rather than luer connections, etc.
Example – Design Change
Adopting a Product
– A larger gauge catheter to the product line could be adopted
without further evaluation.
Change to Product
– The existing validated product is a 20 inch IV Set with one valve
and two injection ports. Product development wants to add a new
IV Set that is 18 inches with one valve and four injection ports.
– In this situation a sub-lethal cycle is a course of action. If the
results are acceptable then the product could adopted into the
cycle.
– Another course would be to compare BIs in the existing
product/PCD to BIs in the proposed product.
Materials & Characteristics – Bioburden Related Issues
Materials & Characteristics – Bioburden-Related
Assess
Issues the impact of the change on the bioburden
– Is the product made in an dirtier environment?
– Does the manufacture involve more human handling,
can’t use gloves?
– Are more biological sources used, are the
components/materials obtained from a supplier that is
not as controlled or operate with the same cleanliness
expectations?
– Is less in-process cleaning done?
Materials & Characteristics – Residual-Related Issues
Evaluate if the change of the material will increase

the residuals levels of the product
– Are the materials the same?
– Are the materials more likely to retain EO?
– Is there something in the manufacturing process that
may affect ECH levels such as:
• Use of bleach/chlorine
• Switch to PVC
Materials & Characteristics – Heat or Humidity
• Evaluate if the change makes the product more

difficult to sterilize
– By making it harder to heat or humidify
• Changes impacting heat transfer
– Increase in wall thickness
– Addition of fluid-filled vials
– Switch to non-absorptive material
Marketing Change – Lap/Vag Sponges
Situation
Marketing wants to add Lap/Vaginal sponges to the
existing Lap/Vaginal product family that are
unbleached cotton so they can promote them as a
“Greener” alternative.
Questions
1. Does the change require testing?
2. If so, what testing would be appropriate? Why?
Marketing Change – Lap/Vaginal Sponges

– Yes
– Bioburden testing
– Sub-lethal cycle evaluating natural product positives to BI and/or
PCDs.
– Removing the bleach is likely to result in an increase the bioburden
of the product.
Manufacturing Change – Waxed
Situation
Product Development and Manufacturing would like to
change the cardboard folder for the existing suture to a
waxed alternative since this will make coiling the suture
easier and reduce shedding in the controlled
environment.
Questions
Manufacturing Change - Waxed

– Yes
– Evaluate humidity levels which could be done in a half cycle with
BIs so that if an issue is found the impact to the BI is determined.
– The waxing of the material may reduce the amount of moisture that
is absorbed affecting levels and lethality.
Package Definitions – Sterile Barrier System
3.44 Sterile Barrier System (SBS)

– Minimum package that prevents
ingress of microorganisms and
allows aseptic presentation of the
product at the point of use.
Package Definitions – Protective Packaging
3.13 Protective Packaging

– Configuration of materials designed to
prevent damage to the sterile barrier system
and its contents from the time of their
assembly until the point of use.
– Typically, shelf cartons, product retainers,
and corrugated shippers.
ANSI/AAMI/ISO 11607-1:2006/(R)2010
Evaluate Packaging Changes Venting
Evaluate the new or changed package to determine if it

results in less venting, is it harder to get moisture or gas to
the product?
– A decrease in porosity because a coating was added, the material
itself is less porous (paper to polyolefin), a label added to the
vented side or the label size increased.
– Layers of packaging material were added, more wraps of CSR, a
second pouch, additional cartons.
– The amount of venting is reduced due to smaller package, change
to pouch header from a strip to a circle.
Example – Shellacked Packaging Change
Proposed Change
– New shipping boxes are being obtained from a new supplier.
These boxes are shellacked on all sides not just where the printing
occurs.
Evaluation
– Perform a half cycle with BIs and temperature/humidity sensors to
evaluate moisture penetration.
Results
– 3 positives BIs were found, the temperature was consistent with
the physical PQ but the humidity range was significantly lower.
Example – Pouch Packaging Change
Proposed Change
– Manufacturing wanted to change the pouch to reduce cost. The
new pouch had a header with 20% less venting.
Evaluation
– Perform a fractional or half cycle with BIs placed as validated to
demonstrate lethality.
Results
– For a fractional cycle the proposed was equivalent or less resistant
than the existing.
– For a half cycle complete kill of all the BIs was observed.
Evaluate Packaging Changes
Bioburden & Product Arrangement

–Does the package affect the product’s bioburden?
–Does the product arrangement obstruct venting?
• Alignment of packages could impact venting
• Evaluate using sub-lethal or half cycle
• May need residual testing
Evaluate Packaging Changes
Functionality
–Will the sterilization process be detrimental to the
packaging?
• Packaging seals withstand vacuum rates
• Cardboard hold up to moisture levels, etc.
• May need physical testing to evaluate packaging
Load Changes – Thermodynamic
Evaluate the thermodynamic response of the load following

the change.
–Is the density significantly different?
–Are additional materials being used, more cases?
–Is there less air space in the pallet?
–Is a greater amount of the chamber volume being occupied by
product?
–Is the pallet configuration more dense, or are there fewer exposed
surfaces?
Load Changes – Humidification
Evaluate the humidification of the load.

– If stretch wrap is used are there more layers or is it
thicker?
– Have water-resistant coatings been added to the
boxes/cartons?
– Has foam or plastic been added to the packaging?
Increase # of Pallets in Load

Situation
Production needs to process more product on a weekly
basis, they want to increase the number of pallets from
two to four.
The PQ was performed with two pallets.
Questions
Increase # of Pallets in Load

– Yes

– The performance qualification will need to be repeated because
the volume of the product has increased.
Change Load Configuration

Situation
– The existing pallet configuration is 3 layers of 12 shipping
boxes per layer in a 4 by 3 pattern, each layer is 18
inches high. The overall pallet density is 100 kg/m3 and
the footprint of the pallet (40” x 48”).
– The pallet configuration for the new product is 4 layers of

16 shipping boxes per layer in a 4 by 4 pattern, each layer
is 13 inches high. The overall pallet density is 100 kg/m3
and the footprint of the pallet (40” x 48”).
– See next slide for pallet diagrams.
Questions
1. Does the change require
testing?
2. If so, what testing would
be appropriate? Why?
Existing Configuration New Configuration

– Probably not
– The new pallet configuration is 64 cartons with pallet dimensions of
40” x 48” x 52”.
– The existing pallet has 36 cartons with pallet dimensions of 40” x
48” x 54”.
– Adoption can be used since the density is the same, the pallet
dimensions are approximately the same and the configuration is
no more difficult for sterilization. However if the amount of
absorptive materials changes greatly then an assessment should
be performed.
Case Study
Determine Course of Action

Instructions
• Use the product given to your group and Annex A of
TIR28, answer the case study questions.
• Provide a conclusion of your evaluation, include:
– Similarities and differences
– Recommended tests/runs, if any
– Overall evaluation
– Rationale
• Select a spokesperson to report your findings
Adoption Comparison Spreadsheet
Questions in Annex A of TIR28 are one way to perform the

adoption comparison
A spreadsheet is another way
See Adoption Comparison Spreadsheet
Retrieve
Document
Summary
• Product Adoption
– Save time and money in the long run with proper
product definition and a careful evaluation of the
changes
• Product Definition
– Determines how the EO processes affect
biocompatibility/stability of materials/products
• Evaluate
– Materials and product characteristics, configuration,
packaging, and load
9. Process Changes/
Equivalence
Module 9 Objectives

–Classify types of process changes
–Evaluate a process change and determine the appropriate actions
–Distinguish between process equivalence and chamber equivalence
–Determine if a process is equivalent in multiple pieces of equipment
Response to the Change
Validation
Process
Requalification
Change
Rationale
Process Change
A change to the sterilization process that results in a different

process for sterilization than originally qualified.
– Process includes preconditioning, sterilization, and aeration
– Equipment
– Location of the sterilization process
Types of Process Changes
Change to the process

– May be dictated by the sterilization facility
– In response to a non-conformance
Change in gas mixture
– Blend to 100% EO
– 100% EO to a blend
– One blend to another
Process optimization
– Improve removal of residuals
– Reduce exposure
Determine Actions Required for Process Change
How will the change affect the process?

– Is lethality potentially impacted
– Will residuals be affected
– What other aspects need to be addressed
Is the impact significant?
– More significant the more qualification or validation is necessary
Example – Nitrogen Blanket Addition
Change
– Addition of a nitrogen blanket after conditioning but before EO
inject
Evaluate
– Temperature and humidification of the load
– Presence of vertical EO/nitrogen stratification and effect on
microbiological lethality from bottom to top of load
– Effect of lower volume percent of EO during EO gas dwell (may
result in a lower diffusion rate)
– Impact of lethality using internal BIs and external PCDs in a sub-
lethal or half cycle
– Any changes in vacuum rates may have an impact on
package/product functionality
Extend Preconditioning
Situation
Due to scheduling flexibility the contractor is asking to
extend the maximum preconditioning time from 48 to 72
hours
Questions
1. How might the change impact the process?
2. How would you plan to evaluate the process to remain
valid?
3. Give a rationale for the plan.
Extend Preconditioning
– The extended Preconditioning time may impact the package or a
product that is moisture sensitive.

valid?
– Evaluate the product/package for functionality.
– However, it is not likely to affect microbiological results so the
change would just require doing a product/package evaluation.
3. Give a rationale for the plan

– Rationale: only a functional rationale is necessary because the
change is not likely to affect microbiological results.
Nitrogen Flush
Situation
For safety purposes the sterilization facility wants to use
nitrogen for the 1st flush following sterilant evacuation
rather than air.
Questions
2. How would you plan to evaluate the process to
remain valid?
Nitrogen Flush
– The potential impact of switching from nitrogen to air is not very
significant assuming that the pressures remain the same.

valid?
– Possible recommendations:
• No further work is needed, or
• A more conservative approach would be to evaluate product residuals
to ensure they are still met.

– Rationale: replacing nitrogen for air is not likely to affect the
sterilization process or its impact to the product.
Equipment Changes
Often equipment changes do not have a significant impact on

the sterilization process.
Contract sterilizer
– Evaluate the change, determine what testing is required, and make
a determination when they think a customer needs to be notified of
the change.
In-house sterilizers
– Similar process
– See Example – Equipment Change Actions
Retrieve
Document
Equipment Change Actions
If the equipment testing performed indicates that there is a

change in the performance of the equipment then testing of
the process may be necessary.
– Vacuum rate or depth
– EO injection rates
– Temperature/humidity ranges or distribution
Vacuum Rate or Depth Equipment Change Actions
Faster Rate Slower Rate

– May impact product or – May extend overall EO
package exposure time
– May remove EO faster – May impact residuals
which could reduce – Testing – full cycle
exposure time
Less Depth
– May increase product
residuals – Affect entire cycle
– Testing – MPQ cycle, full – Resulting in a new
cycle performance qualification
EO Injection Rates Equipment Change Actions
Faster Rate Slower Rate

– May result in less – May result in longer EO
overall EO exposure exposure affecting
affecting lethality residuals
– Testing – MPQ cycle – Testing – Full cycle
Temperature/Humidity Equipment Change Actions
Wider Range Narrow Range

– May impact temperature or – No impact
humidity of load to lower
than validated
• Perform temperature/
humidity profile in half
cycle
• If change is noted, then
lethality is determined
– Higher temperature range
• May impact product if it
is temperature and/or
moisture sensitive
Temperature/Humidity Equipment Change Actions
Distribution within chamber/room different

– Hot/cold spots moved
– May need to evaluate with a temperature/humidity
profile
Equipment Change
Situation
A new vacuum pump (not rate controlled) is installed.
Testing shows that the vacuum rate is greater than the
previous pump but the validated vacuum depth cannot be
achieved.
Questions
2. How would you plan to evaluate that the process will
remain valid?
Equipment Change

– A faster vacuum rate may affect the product or package.
– It may also mean that EO is removed faster reducing the overall
exposure time.
– Also sometimes a faster vacuum rate may result in an increase in
product residuals. The entire cycle would be affected by the
shallower vacuum.
Equipment Change
2. How would you plan to evaluate that the process will

remain valid?
– Conduct a performance qualification (microbiological and
physical).

– The PQ will demonstrate that the process remains lethal and that
the product aspects such as functionality, residuals, and package
integrity are acceptable.
Location Changes
• Different sterilizer at the same facility

• Different facility
– City
– County
– Country
• Has process equivalence been established between
locations?
Evaluate Location Capability
• Will the sterilization facility meet your needs and

specifications?
• Can they accommodate your volumes?
• Do they have all the equipment that your process
requires: preconditioning, sterilizer, sensors, heated
aeration, etc.?
• Do they process with the same gas mixture?
• Can they run the same process or do they need to make
changes?
• Do you/they comply with the regulations? Will they
comply with your company’s internal requirements?
Definition – Process Equivalence
Process Equivalence is method used to demonstrate that the

same validated sterilization process is delivered by two or more
pieces or sets of equipment. It does not require that the
equipment be physically identical. Even if the parameters
delivered by the equipment are not statistically identical, the
processes delivered can still be equivalent if they are all
capable of running the process within the defined, validated
process limits (AAMI TIR 28[26]).
ANSI/AAMI/ISO 11135:2014 (D.12.5.1)
Process Equivalence vs. Chamber Equivalence
Process Equivalence Chamber Equivalence

– Shows equivalence of the – Shows equivalence of
process as it performs in the equipment
the equipment with the – Identical equipment not
load in place necessarily equivalent
– Includes preconditioning &
aeration
– Chambers/rooms that are
not identical can be shown
to be equivalent in process
Process Equivalence
12.5.1 Process Equivalence

Sterilization equipment that delivers the same process
parameters, having undergone IQ and OQ, shall be qualified
either
a) in the same manner as the original chamber, or
b) using a reduced MPQ that demonstrates the delivery of the
required level of microbiological lethality and PPQ to
demonstrate temperature and humidity uniformity of the load
and control by the production chamber. The rationale for this
reduced qualification shall be recorded and documented.
Process Equivalence
12.5.1 Process Equivalence

The influence of different geographical locations on the
product or load properties shall be determined.
Establishing Process Equivalence
Process Analysis & Microbiological

Evaluation Evaluation
(ISO 11135:2014 and (ISO 11135:2014 and
AAMI TIR28:2016) AAMI TIR28:2016)
Evaluation of
Performance of
preconditioning
a sub-lethal or
or aeration
MPQ cycle
areas
Evaluation of
sterilization
chamber
performance
Example - Process Equivalence
Situation
– Different location
– Process includes preconditioning, sterilization, aeration
– Sterilization chambers are different sizes
Validation
– See “Example Process Equivalence Validation #100”
Retrieve
Document
Example – Process Analysis & Evaluation
• The temperature/humidity spread after preconditioning

met the acceptance criteria.
• The minimum humidity and spread after conditioning met
the acceptance criteria.
• The temperature spread at the end of Gas Dwell met the
acceptance criteria.
• The minimum product temperature in aeration was met.
• The results of the process analysis and evaluation
indicate that the sterilization process performed in the
candidate equipment was equivalent to the sterilization
process in the existing equipment.
Example – Microbiological Evaluation
• The product is a biopsy tray with a moistened cotton pad

that is packed non-sterile. It is probable this product
would support microbial growth.
• The results of the microbiological evaluation indicated

that there is a potential impact to the lethality of the
sterilization process due to the equipment/location
change since the bioburden of the product may increase.
• The results of the half cycle indicate that the internal and
external BI challenge was killed; therefore, the
determination is that they are equivalent.
Example – Optional Design & Engineering Evaluation
• The preconditioning room is larger, farther from the

sterilizer, the temperature/humidity range is wider, the
humidity set point is less, and the rooms use completely
different utilities.
• The sterilizer is larger, the equilibration time was longer,
and the placement of the EO/steam headers is different.
• The aeration room is larger, the temperature range is
wider, the set point is higher, and the rooms use
completely different utilities.
• The results of Phase 1, the design and engineering
evaluation, indicate that the candidate equipment is not
equivalent to the existing equipment.
Example – Process Equivalence
Conclusion
The results of the design and engineering evaluation indicated that
the processes were not equivalent but the microbiological
evaluation testing and the results of the process equivalence study
demonstrated that the processes were equivalent. Therefore the
processes can be considered equivalent. No additional
microbiological PQ runs will need to be performed because the half
cycle was used during the microbiological evaluation.
Case Study
Process Equivalence
Instructions
– Work in assigned groups.
– Select a spokesperson to share
your group’s findings.
– Read the assigned case.
Determine if the process is
equivalent.
• Evaluate each phase for equivalency.
• Give your rationale for each phase.
• Write the validation conclusion for the
case.
Case Study
Process Equivalence
Determine if the processes are equivalent
– Validation Number: 101
• Same location
• Process does not include preconditioning
• Aeration is in the same chamber
– Validation Number: 102
• Same location
• Same sterilization chamber
• Different preconditioning and aeration chambers
being evaluated
Process Equivalence
Case 101
Case 101 - Equivalency to Evaluate

– Same location, process does not include preconditioning, and
aeration is in the same chamber.
Process Analysis & Evaluation

– The process would be considered Not Equivalent based on the
comparison of the load humidity and temperature levels and
ranges.
Process Equivalence
Case 101
Microbiological Evaluation
– The microbiological evaluation resulted in an Equivalent
determination since the results of the sub-lethal cycle were
consistent with those found in the existing vessel. In addition there
should be no changes to the level of bioburden on product prior to
sterilization.
Conclusion
– The overall process would be considered Not Equivalent based
on the finding that the process analysis and evaluation was
considered not equivalent.
Process Equivalence
Case 102
Case 102 - Equivalency to Evaluate

– Same location, same sterilization chamber, different
preconditioning and aeration chambers being evaluated.
Process Analysis & Evaluation

– The preconditioning area may be considered Equivalent since the
load humidity and temperature spreads met the acceptable range
for the process.
Process Equivalence
Case 102
Microbiological Evaluation
– The microbiological evaluation resulted in a Not Equivalent
determination based on the results. See Table 1 – Sub-lethal
Results.
Conclusion
– The overall conclusion would be determined based on the
conclusion of the microbiological evaluation, which is that the
processes are Not Equivalent.
Summary
Process changes include

– Process, equipment and location
Process equivalence
– Not chamber equivalence
– Includes preconditioning, aeration, and/or sterilization cycle
– The load must be taken into consideration
– Identical equipment does not necessarily mean equivalence
– AAMI TIR28:2016
– ANSI/AAMI/ISO 11135:2014

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ABOUT AAMI

The Association for the Advancement of Medical Instrumentation (AAMI) is a nonprofit

• Courses, conferences, and continuing education, including certification programs.

AAMI is a not-for-profit association whose programs include the development of voluntary

Printed in the United States. Updated 3/22/2016.

Industrial Ethylene Oxide

AAMI is a nonprofit organization of over 7,000 members.

AAMI fulfills its mission through:

4301 N. Fairfax Drive, Suite 301 tel. 703-525-4890

•Emergency contact form

• Ethylene Oxide Sterilization for Medical Devices

Faculty for AAMI’s training programs are drawn from an

At the end of this workshop, you should be able to:

Module 1 Validation and Requalification

Module 6 Ethylene Oxide Residuals

At the end of this module, you will be able to:

Installation Operational Performance

• Contractor • Contractor • Contractor

•Make sure all equipment calibrated prior to OQ

•Performed in the equipment to be used to sterilize the

Installation Operational Performance

Comparative resistance or sub-lethal

•Test system containing

•For EO the viable

•Demonstrates that the sterilization process meets

Annex A of ANSI/AAMI/ISO 11135

Installation Operational Performance

Demonstrates reproducibility of the process

Specified acceptance criteria are met throughout the

9.4.3.2 PPQ shall confirm the process such that:

9.4.3.2 PPQ shall confirm the process such that:

9.4.3.2 PPQ shall confirm the process such that:

process remains valid

Requalification shall verify

Figure D.1 – Requalification decision tree

D.12.3.2 - ANSI/AAMI/ISO 11135:2014

• Periodic requalification of equipment:

Full • Conduct PPQ

• One Fractional/Half Cycle including load

Documented • Document justification

•Verify paper review every two years by performing

Different product mix

1. Which of the 3 requalification options would be most

2. Based on the requirements for requalification, what are

–Also, because the temperature sensor in the preconditioning

•Document all assessments

Section 5.3 Sterilization Process & Equipment Assessment

Section 5.4 Product & Process Assessment

•Address any acceptance criteria

Writing Conclusion for Annual Assessment for

Writing Conclusion for Product 2 Annual Assessment

Writing Conclusion for Product 2 Annual Assessment

Writing Conclusion for Product 2 Annual Assessment

Writing Conclusion for Product 2 Annual

Writing Conclusion for Product 2 Annual Assessment

7.4 Overall Conclusion

7.4.3 A full cycle to confirm the product residual levels

• Sterilization validation consists of Installation

At the end of this module, you will be able to:

9.5.1 The purpose of this activity is to

Clear purpose, scope, or objective

Rationale or basis documented

Equipment, materials specified

Meaningful acceptance criteria