autoclave qualification some practical advice

7/21/2019 Autoclave Qualification Some Practical Advice

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Special Edition: Utilities Qualification 149

utoclaveQualification

Some

Practical

Advice

By Gamal Amer Ph.D.

Robert G. Beane Jr.

Validation and Process Associates

------------------------------------t\-----------------------------------

D

espite the fact that the sub

ject

of

autoclave qualifica

tion has been the topic of

numerous articles, books, and sym

posia in the past decade, autoclave

qualification shortcomings are a

mong the leading source of FD 483

citations reported for the biotech

industry. This article attempts to pre

sent a hands-on approach to efficient

ly and reliably qualify autoclaves .

This article assumes that the reader is

somewhat familiar with the basic the

oretical development of steam steril

ization 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 In

stallation and Operational Qualification IQ/OQ) to

also serve as the commissioning and start-up docu

ment

is

a practice that

has

recently gained populari

ty,

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 start

up function, failures and deviations from protocol

acceptance criteria will

most

likely result thus in

creasing cost. A better approach for saving time and

money would

be

to consider all the operational re

quirements for the autoclave prior to ordering and

commissioning the autoclave with

qualification

expected to

verify

these functional requirements . Such

an approach would also avoid du

plication

of

effort and lead to a

smooth qualification. A factory ac

ceptance 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 work

ing condition before the qualifica

tion phase can proceed.

Prior to beginning the qualifica

tion effort, assessments of the mater

ial being autoclaved should be made for cycle devel

opment. Some parameters to consider are susceptibil

ity 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 pat

terns should be established, assigned to cycles, and

tested. These tests should verify, at a minimum, tha

the load was not affected by the heat profile, the con

tainer integrity has not been compromised, and the

sterility of the load has been achieved. This is typical

ly done by a combination of heat penetration studie

and biological testing.



Special Edition: Utilities Qualification150

Installation Qualification IQ)

Upon completion

o

the load and cycle develop

ment, the IQ phase is initiated. Equipment IQs are gen

erally similar and vary little from one kind o equip

ment to another. Therefore, the IQ portion

o

the qual

ification will not be emphasized in this discussion. In

general, the IQ may verify the following information:

1 Equipment specifications: verification o pri

mary system components.

2. Component/Auxiliary equipment specifica

tions: verification o secondary system com

ponents.

3. Instrument specifications and calibration:

verification o associated critical and non

critical instruments.

4. Materials

o

construction: verification

o

product and non-product contacting surfaces.

5. Filter schedules: verification o system fil

ters with associated replacement procedures.

6. Control systems: verification o system con

trol type and necessity for individual control

system qualification.

7. Utility connections: verification that required

utilities are installed as required.

8. Design specifications and drawings: verifica

tion o system specifications and associated

diagrams.

9. Installation documentation and drawings: ver

ification o system schematics and as-built

diagrams.

10. Standard Operating Procedures SOPs) and re

lated programs: verification of approved SOPs

for start-up, shutdown, operation, preventive

maintenance, cleaning, calibration, and change

control.

11. Certification documents: verification o all

certifications resulting from the installation

o

the system.

12. Required training documents and procedures:

verification

o

the establishment and imple

mentation

o

approved training procedures.

Documents and manuals should be reviewed thor

oughly to confirm and assure that the information col

lected during the IQ phase

o

the qualification effort

is accurate and contradictions

do

not occur.

Gamal Amer Ph.D. and Robert

G

Beane Jr.

Operational Qualification OQ)

Depending on the complexity o the autoclave

control system, a variety o different tests should be

performed during the OQ portion o the qualifica

tion effort. The most important issue to keep in mind

when conducting the OQ

is

temperature mapping

o

the empty chamber.

Empty chamber tests, which should be performed

to verify the proper operation o 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 o thermo

couples, depending on the volume

o

the chamber,

should be distributed to establish the temperature

profile within the chamber and verify that there is a

minimum

o

temperature differential and fluctuation

during a cycle. The thermocouples should be:

• 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 temper

ature sensing capabilities o the thermocouples.

• positioned at the extremities

o

the chamber,

but slightly off the surface o the inside cham

ber; two to four inches, depending on the size

o the autoclave, is usually sufficient.

Other important factors to consider when devel

oping tests for an autoclave OQ include:

• Control system setup: Is the system set up to

operate by recording the Fo value o a control

thermocouple or by ramping and holding a

temperature for a period o time?

• System safety features: Are there locks on the

autoclave doors during pressurization cycles?

Should the system enter a slow exhaust mode i

shut down during a run? Does the system sound

an audible alarm when the cycle is complete?

• Quality o cooling water or air injects: Any me

dium that comes in contact with the sterilized

load should be shown to contain a low biobur

den and be part o a monitoring program.

• Vacuum and/or relative pressurization: Chamber



Special Edition: Utilities Qualification 151

operation while running loaded chambers and assess

ing the minimum lethality levels. In addition, these

tests should be developed to verify the heat penetra

tion throughout the load and the sterility level

reached. Tests conducted during a PQ are normally

comprised

o

two components; heat penetration stud

ies and biological challenge tests. The heat penetra

tion studies are performed to verify that each position

within the load is exposed to sufficient heat for prop

er 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

o

the chamber extremities.

Thermocouples should be strategically distrib

uted within the load with the purpose

o

measuring

the temperature and lethality at the locations that

may represent the most difficult heat penetration sit

uation. 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

o

the

thermocouple wires should ensure that the thermal

center o 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 i allowed.

The biological challenge tests are conducted at

the same time as the penetration studies by means

o

Biological Indicators (BIs). These BIs can be ob

tained in a variety

o

different types, including

ampoules, spore strips, discs, and suspensions. Re

gardless

o

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

o

1

6

are used. How

ever, other commercial BIs are available for moist

heat sterilization studies that are comprised

o

other

organisms such as B. subtilus B. coagulans and C

sporogenes

with populations from

1

3

to 1

9

and

possibly higher. BI requirements depend on the par

ticular load and sterilization requirements. However,

justification should be provided at the time o quali

fication. When conducting the studies, the BIs

should, at a minimum, be placed in the components

adjacent to the thermocouples, but ideally

as

close as

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

possible to the thermal areas, which are being mea

sured by the thermocouples. Tests are typically con

ducted 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.

inal Reports

Final reports, summarizing the results

o

the stud

ies, should be generated after completion

o

each

qualification step. All raw data generated, including

biological indicator growth results, should be attach

ed to the executed protocol. Autoclave re-qualifica

tion should occur periodically, according to estab

lished change control procedures and with associated

test protocols, to verify that the autoclave has re

mained in a validated state.

Summary

In summary, autoclave qualification is a fact

o

life in the pharmaceutical and biotechnology in

dustries, but doesn t have to be a source

o

stress

i

the system qualification is carefully thought out and

approached logically. The confirmatory nature

o

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 manufactur

er specifications, calibrated, connected to appropriate

utilities, and have associated diagrams and SOPs

established and available. The autoclave control sys

tem should be tested by means

o

logical system tests

to verify proper system operation and temperature

distribution. Furthermore, temperature penetration

tests and biological challenge tests should be per

formed to confirm the sterility

o

the materials afte

undergoing an established cycle. 0



Special Edition: Utilities Qualification152

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