Performance Qualification Performance Qualification of a vial washerof a vial washer

ContentsContents

Introduction-DQ, IQ, OQ, PQ

Performance Qualification of a vial washer

IntroductionIntroduction

DQ(Design Qualification)

IQ(Install Qualification)

OQ(Operation Qualification)

PQ(Performance Qualification)

Performance Qualification Performance Qualification of a vial washerof a vial washer

The importance of PQ for a vial washer

Performance of the vial washer should be qualified. Alt

hough 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, althoug

h there are no pyrogens present.

Performance Qualification Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof a vial washer

Provision -21CFR Part 211.94

Drug product containers and closures shall be clean a

nd, 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 Performance Qualification of a vial washera vial washer

Provision -The FDA Guideline for Dosage Form

Drug Manufacturers Determine how containers and closures are handled a

nd stored. Decide if the cleaning, sterilization, and depyrogenizat

ion are adequate, and have been validated.

Performance Qualification Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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, m

edia 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof 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 Performance Qualification of a vial washerof a vial washer

Conclusion The PQ testing of the washer is essential to ensure the eli

mination of contamination from the vials itself. The quantitative decontamination study can provide a hig

h 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 Performance Qualification of a vial washerof 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.