hello,Good day for all,
How to Qualify vial washing machine.what kinds of tests are to be carried out to qualify the vial washing machine.Is there is any guideline about tempelate of PQ protocol.
This may be useful
A vial washer is a relatively simple machine commonly used to clean containers during the manufacture of dosage form drugs. Some drug manufacturers only perform Installation Qualification (IQ) and Operational Qualification (OQ) of the machine as no regulatory requirements clearly state that the 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. 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.
21CFR Part 211.94 states: “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.”
The FDA Guideline for Dosage Form Drug Manufacturers also states:” Determine how containers and closures are handled and stored. Decide if the cleaning, sterilization, and depyrogenization are adequate, and have been validated.” So drug manufacturers have to evaluate the cleaning capability of the vial washer for endotoxin, as well as for chemical substance and particulate.
Then, where do you begin the validation?
The IQ/OQ of the machine should be performed prior to the Performance Qualification (PQ). As IQ/OQ is simple, and most drug manufacturers already have already conducted these tests, let’s focus on the topic of performance qualification
Before showing how we conducted the validation, it is better to give a brief description of our vial washer. 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 (compressed air for stations one and eight, recycled water for stations two and four, deionized water stations for five and six, and Water-for-Injection [wfi] for station seven). 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.
Two questions will help us design the PQ study:
• First, which parameters 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.
• Second, what’s the purpose of washing?
As mentioned above, 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. 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.
Questions may arise regarding the contamination level before washing and the acceptance level after washing. The initial contamination level of vials from qualified vendors was tested to set up the deliberate contamination level of the study. 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. 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.
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Thus three decontamination studies were performed for each kind of vials. 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.
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. 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.
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.
It should be emphasized that all these validation studies are performed under worst-case conditions as mentioned previously.
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. 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.
Also from Figure 4, we can find that there is no obvious difference for residual endotoxin level in those testing vials from the beginning, middle, and end of the washing process. It demonstrates that the performance of the machine is quite stable during the whole washing process.
Conclusion
In 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. 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.
About the Author
Lu Liqiang is Quality Assurance Manager of Rhodia Wuxi Pharmaceutical Co., Ltd. He has over 10 years in the pharmaceutical industry in areas that include manufacturing, marketing, technical services, and quality assurance. Mr. Liqiang specializes in the validation of equipment, utilities, manufacturing, and cleaning processes. He can be reached by phone at 086-510-3266266-202, by fax at 086-510-3263993 or e-mail at Liqiang.Lu@ap.rhodia.com
Suggested Reading
[LIST=1]
OQ: Operational Qualification
PQ: Performance Qualification
WFI: Water-for-Injection
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dear all,
I have a problem,
we has a vial washing machine with ultrasonic bath.and I am prepering to write to operational qualification of vial washing machine,however,i haven’t any information of ultarasonic bath and how to verify ultrasonic bath in washing machine.
Is there is any guideline about tempelate of baths verification?
right now Thanks for your help.
[quote=tuti]dear all,
I have a problem,
we has a vial washing machine with ultrasonic bath.and I am prepering to write to operational qualification of vial washing machine,however,i haven’t any information of ultarasonic bath and how to verify ultrasonic bath in washing machine.
Is there is any guideline about tempelate of baths verification?
right now Thanks for your help.[/quote]
Well, I think this bath functions for heating water at a certain temperature and definitely it wud be operated by control panel, may be some safty precautions wud b there as ultrasonic rays are hazardous in open environment, Anyway the prime objective is to check and control temperature like the maximum and minimum set values, safety alarams in case of overshooting.
sir, can you give me the validation protocol for vial washing.
thanks.
regards,
nida
there is no need ov validating awashing machine for endo toxin reduction as per FDA