Transcript Performance Qualification of a vial washer

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)
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OQ(Operation Qualification)
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PQ(Performance Qualification)
Performance Qualification
of a vial washer
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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
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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
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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 crosscontamination 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
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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
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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 100010,000EU 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
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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
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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.