Autoclave Qualification Some Practical Advice

Autoclave Qualification:
Some Practical Advice

By Gamal Amer, Ph.D.
&
Robert G. Beane, Jr.
Validation and Process Associates
------------------------------------t\----------------------------------f
espite the fact that the subject of autoclave qualification has been the topic of
numerous articles, books, and symposia in the past decade, autoclave
qualification shortcomings are among the leading source of FDA 483
citations reported for the biotech
industry. This article attempts to present a hands-on approach to efficiently and reliably qualify autoclaves.
This article assumes that the reader is
somewhat familiar with the basic theoretical development of steam sterilization and equipment qualification.
Autoclave qualification, or for
that matter qualification of any piece
of equipment, should begin after the
equipment is installed and fully
commissioned. Designing the Installation and Operational Qualification (IQ/OQ) to
also serve as the commissioning and start-up document is a practice that has recently gained popularity, but is not recommended. Such thinking arose
because organizations believe that it will lead to
time as well as resource saving. However, when
qualification serves as the commissioning and startup function, failures and deviations from protocol
acceptance criteria will most likely result thus increasing cost. A better approach for saving time and
money would be to consider all the operational requirements for the autoclave prior to ordering and
commissioning the autoclave with

qualification expected to verify
these functional requirements . Such
an approach would also avoid duplication of effort and lead to a
smooth qualification. A factory acceptance test, prior to receiving the
autoclave at the facility, should be
performed. Once the autoclave is
installed, it should be rigorously
commissioned and then started. In
other words, the autoclave should
be thoroughly tested during the
commissioning and start-up phase.
All bugs must be fixed, and the
autoclave must be in proper working condition before the qualification phase can proceed.
Prior to beginning the qualification effort, assessments of the material being autoclaved should be made for cycle development. Some parameters to consider are susceptibility of the load to the heating conditions, maintenance
of sterility after autoclaving, differences in solids and
liquids heating, and the effect of trapped air. Load patterns should be established, assigned to cycles, and
tested. These tests should verify, at a minimum, that
the load was not affected by the heat profile, the container integrity has not been compromised, and the
sterility of the load has been achieved. This is typically done by a combination of heat penetration studies
and biological testing.
Special Edition: Utilities Qualification
149
Gamal Amer, Ph.D. and Robert G. Beane, Jr.
Installation Qualification (IQ)
Operational Qualification (OQ)
Upon completion of the load and cycle development, the IQ phase is initiated. Equipment IQs are generally similar and vary little from one kind of equipment to another. Therefore, the IQ portion of the qualification will not be emphasized in this discussion. In
general, the IQ may verify the following information:
Depending on the complexity of the autoclave

control system, a variety of different tests should be
performed during the OQ portion of the qualification effort. The most important issue to keep in mind
when conducting the OQ is temperature mapping of
the empty chamber.
1. Equipment specifications: verification of primary system components.

2. Component/Auxiliary equipment specifications: verification of secondary system components.
3. Instrument specifications and calibration:
verification of associated critical and noncritical instruments.
4. Materials of construction: verification of
product and non-product contacting surfaces.
5. Filter schedules: verification of system filters with associated replacement procedures.
6. Control systems: verification of system control type and necessity for individual control
system qualification.
7. Utility connections: verification that required
utilities are installed as required.
8. Design specifications and drawings: verification of system specifications and associated
diagrams.
9. Installation documentation and drawings: verification of system schematics and as-built
diagrams.
10. Standard Operating Procedures (SOPs) and related programs: verification of approved SOPs
for start-up, shutdown, operation, preventive
maintenance, cleaning, calibration, and change
control.
11. Certification documents: verification of all
certifications resulting from the installation
of the system.
12. Required training documents and procedures:
verification of the establishment and implementation of approved training procedures.
Empty chamber tests, which should be performed

to verify the proper operation of the autoclave, are
normally designed to test and determine the hot and
cold spots for thermocouple placement. During an
empty chamber run, a sufficient number of thermocouples, depending on the volume of the chamber,
should be distributed to establish the temperature
profile within the chamber and verify that there is a
minimum of temperature differential and fluctuation
during a cycle. The thermocouples should be:
Documents and manuals should be reviewed thoroughly to confirm and assure that the information collected during the IQ phase of the qualification effort
is accurate and contradictions do not occur.
150
positioned throughout the chamber and within

the anticipated hot and cold regions, the steam
inlet, and condensate drain.
held in position with heat resistant tape, or a
similar material that will not affect the temperature sensing capabilities of the thermocouples.
positioned at the extremities of the chamber,
but slightly off the surface of the inside chamber; two to four inches, depending on the size
of the autoclave, is usually sufficient.
Other important factors to consider when developing tests for an autoclave OQ include:
Control system setup: Is the system set up to
operate by recording the Fo value of a control
thermocouple or by ramping and holding a
temperature for a period of time?
System safety features: Are there locks on the
autoclave doors during pressurization cycles?
Should the system enter a slow exhaust mode if
shut down during a run? Does the system sound
an audible alarm when the cycle is complete?
Quality of cooling water or air injects: Any medium that comes in contact with the sterilized
load should be shown to contain a low bioburden and be part of a monitoring program.
Vacuum and/or relative pressurization: Chamber
Gamal Amer, Ph.D. and Robert G. Beane, Jr.
operation while running loaded chambers and assessing the minimum lethality levels. In addition, these
tests should be developed to verify the heat penetration throughout the load and the sterility level
reached. Tests conducted during a PQ are normally
comprised of two components; heat penetration studies and biological challenge tests. The heat penetration studies are performed to verify that each position
within the load is exposed to sufficient heat for proper sterilization. These tests are conducted in a manner
similar to the OQ empty chamber tests, except that
the thermocouples are positioned within the load
instead of the chamber extremities.
Thermocouples should be strategically distributed within the load with the purpose of measuring
the temperature and lethality at the locations that
may represent the most difficult heat penetration situation. Special care should be taken to monitor large
thermal masses, highly insulated components, and
all product-contacting surfaces. Once these locations
have been identified, the actual placement of the
thermocouple wires should ensure that the thermal
center of the component is measured and that no
harm comes to the thermocouples. Load carts and
metal covers can easily damage thermocouple wires
and ruin tests if allowed.
The biological challenge tests are conducted at
the same time as the penetration studies by means of
Biological Indicators (BIs). These BIs can be obtained in a variety of different types, including
ampoules, spore strips, discs, and suspensions. Regardless of the type chosen, positive controls should
be collected for each test performed. Special care
should be taken to record the organism's name, the
BI supplier, spore population, lot number, expiration
date, and specific resistance information. Typically
in autoclave qualification, B. stearothermophilus
BIs with a spore population of 106 are used. However, other commercial BIs are available for moist
heat sterilization studies that are comprised of other
organisms such as B. subtilus, B. coagulans, and C.
sporogenes with populations from 103 to 109 and
possibly higher. BI requirements depend on the particular load and sterilization requirements. However,
justification should be provided at the time of qualification. When conducting the studies, the BIs
should, at a minimum, be placed in the components
adjacent to the thermocouples, but ideally as close as
possible to the thermal areas, which are being measured by the thermocouples. Tests are typically conducted multiple times and with worst-case scenarios
in mind. However, it is strongly recommended that
tests be conducted at a minimum in triplicate for
each load pattern.
Final Reports
Final reports, summarizing the results of the studies, should be generated after completion of each
qualification step. All raw data generated, including
biological indicator growth results, should be attached to the executed protocol. Autoclave re-qualification should occur periodically, according to established change control procedures and with associated
test protocols, to verify that the autoclave has remained in a validated state.
Summary
In summary, autoclave qualification is a fact of
life in the pharmaceutical and biotechnology industries, but doesn't have to be a source of stress if
the system qualification is carefully thought out and
approached logically. The confirmatory nature of
validation suggests that the system's operation
should be known prior to conducting qualification
tests. Once installed, load development tests should
be run to establish a baseline for the system. Once
established, the system qualification can start. The
system should be installed according to manufacturer specifications, calibrated, connected to appropriate
utilities, and have associated diagrams and SOPs
established and available. The autoclave control system should be tested by means of logical system tests
to verify proper system operation and temperature
distribution. Furthermore, temperature penetration
tests and biological challenge tests should be performed to confirm the sterility of the materials after
undergoing an established cycle. 0
151
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Autoclave Qualification:

Some Practical Advice

commissioning the autoclave with

Gamal Amer, Ph.D. and Robert G. Beane, Jr.

Installation Qualification (IQ)

Operational Qualification (OQ)

Depending on the complexity of the autoclave

1. Equipment specifications: verification of primary system components.

Empty chamber tests, which should be performed

Special Edition: Utilities Qualification

positioned throughout the chamber and within

Gamal Amer, Ph.D. and Robert G. Beane, Jr.

Special Edition: Utilities Qualification

Save 20% Off the Regular Price of $99.00

Defines FDA terminology and compares it to

Special Edition: Utilities Qualification

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