Performance Qualification

of a vial washer
 Contents

• Introduction-DQ, IQ, OQ, PQ

• Performance Qualification of a vial washer

 Introduction

• DQ(Design Qualification)

• IQ(Install Qualification)

• OQ(Operation Qualification)

• PQ(Performance Qualification)
 Performance Qualification
of a vial washer
• The importance of PQ for a vial washer

Performance of the vial washer should be qualified.

Although depyrogenation may be achieved using a
heating tunnel or oven, if the washing process cannot
remove chemical contaminants or particles, they will
produce a pyretic response in humans or animals,
although there are no pyrogens present.
 Performance Qualification
of a vial washer
• The importance of PQ for a vial washer

Some drug manufacturers may perform a qualitative trace

study for coloring matter in washed vials using a white wiper
to verify the performance of the washer, but it is not a
quantitative method to reflect the actual performance of the
washer for particles,endotoxin, and chemical contaminants.
 Performance Qualification
of a vial washer
• Provision
-21CFR Part 211.94

Drug product containers and closures shall be clean and,

where indicated by the nature of the drug, sterilized and
processed to remove pyrogenic properties to assure that
they are suitable for their intended use.
 Performance Qualification of a vial washer

• Provision
-The FDA Guideline for Dosage Form
Drug Manufacturers

Determine how containers and closures are handled and

stored.
Decide if the cleaning, sterilization, and depyrogenization
are adequate, and have been validated.
 Performance Qualification
of a vial washer
• A brief description of our vial washer (LIBRA
HYDRA1000-7-B)

Our automatic vial washers (LIBRA HYDRA1000-7-B) are

designed to wash externally and internally many kinds of
glass or plastic cylindrical containers.

There are eight washing stations, plus two dripping

stations equipped with independent connections to their
respective circuits to prevent cross- contamination
among the various media.
 Performance Qualification
of a vial washer
• A brief description of our vial washer (LIBRA
HYDRA1000-7-B)

Each station has seven washing channels.

When washing, the needles on each station enter the
vials as the various media are sprayed.
Each washing channel may have a different spray
strength due to the distance of the spray nozzle from the
utility supply point.
Media spray time can be individually adjusted according
to bottle size and production speed.
 Performance Qualification
of a vial washer
• Designing of PQ Study
Parameters which will affect the ability of the
cleaning
The ability of cleaning is largely dependent on vial size,
media spray time, and pressure and washing speed.
So each size of the vials will be subjected to the PQ
study.
To incorporate the worst case scenario into the validation
studies, higher washing speed (+10%), shorter media
spray time (-10%), and lower media spray pressure (-
10%) than the pre-established washing cycle will be
implemented during validation.
 Performance Qualification
of a vial washer
• Designing of PQ Study
what’s the purpose of washing?
The vial washer is used to clean the drug container to
eliminate the contamination (endotoxin, chemical
substance, particles etc.) from the container itself to
ensure that the products produced meet expectations for
purity, identity, safety, and quality.
Thus decontamination studies for endotoxin, chemical
contaminants, and particles should be performed.
 Performance Qualification
of a vial washer
• Designing of PQ Study
what’s the purpose of washing?
As the internal surface of the vial is product-direct contact,
a certain quantity of each contaminant will be placed into
the vials, and washed in the vial washer.
Then the quantity of contaminants in each washed vial
will be determined, thus the reduction of contaminants
can be obtained to verify the machine performance.
 Performance Qualification
of a vial washer
• Questions regarding with the contamination
level before washing and the acceptance level
after washing
The initial contamination level was obtained by testing
samples taken from three different production lots
according to Military Standard 105E.
In this case, for endotoxin, the initial level is quite low, and
the depyrogenation process of dry heat will ensure the
endotoxin reduction, so we use 1000-10,000EU as the
initial level, and set acceptance criteria at three log
reduction of 1000EU.
 Performance Qualification
of a vial washer

For particle and chemical substance (free alkali), we

double the data averaged from the test results of the
initial contamination level testing.
As any particle or chemical contaminants may affect the
quality of the products, the acceptance criteria should be
free of particles and chemicals for washed vials.
Thus three decontamination studies were performed for
each kind of vials.
 Performance Qualification
of a vial washer

Each study was challenged three times to verify the

reproducibility of the machine’s performance.
Preparation procedures of contaminated testing vials for
each study and their acceptance criteria are listed in
Figure 1.
 Performance Qualification
of a vial washer

For each study, the quantity of vials to be washed is the

same as normal production size to demonstrate the
performance of the normal process.
Those 280 contaminated vials were divided into four
groups.
The first group is put at the beginning of the washing
process, the second and third group is put in middle of
the process randomly, while the fourth group is
scheduled at the end of the washing process.
 Performance Qualification
of a vial washer

Each group contained 70 vials in 10 rows, each row

containing seven contaminated vials washed on each
washing channel.
To ensure each washing channel will be challenged and
easy to analyze in the case of failure, these
contaminated testing vials were marked consecutively,
and deliberately arranged as specified in Figure 2.
 Performance Qualification
of a vial washer

The washed vials were carefully collected with gloves,

tweezers, placed into identified, particle-free cleaning
bags as they exited the washer, and sent to the
laboratory for testing.
As outside contamination will significantly affect the test
results, special attention was required during the
collection of the vials.
 Performance Qualification
of a vial washer
Laboratory test results for the washed vials demonstrated
the high efficiency of the machine.
Testing vials for particle decontamination study were all
free of particles and testing vials for the chemical
decontamination study are all free of sodium chloride.
Three log endotoxin reductions were achieved for each
endotoxin decontamination study.
Further analysis of the results for residual endotoxin
demonstrated the performance of the vial washer.
The average testing results for vials washed at different
locations show an obvious trend as illustrated in Figure 3.
 Performance Qualification
of a vial washer

It appears to be nearly a 400% variation in performance

between Channel number one and Channel number
seven.
This is due to the distance of the spray nozzle from the
utilities supply point.
The closer channel has the higher washing efficiency due
to the high pressure of media when sprayed out.
There is a consideration to add a utility supply point at the
other side of each washing station to increase the
pressure of sprayed media at locations five, six, and
seven to ensure a more uniform performance.
 Performance Qualification
of a vial washer
• Conclusion

The PQ testing of the washer is essential to ensure the

elimination of contamination from the vials itself.
The quantitative decontamination study can provide a
high degree of assurance to validate the performance of
the washer with presetting parameters.
Requalification of the washer is not necessary if no
change occurs.
Of course, in case of any changes on the vials or
washing parameters, the washing cycles applied should
undergo PQ testing again.
 Performance Qualification
of a vial washer
• Conclusion(continue)

Periodic initial contamination testing for supplied vials is

recommended to ensure all vials to be washed are still
under validated conditions.
Periodic testing of washed vials especially coming off
Channel number five to seven is also advisable.