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What are the corrective actions to be taken incase of there is any oos or breakdown in stability studies due to failure of results or due to other equipment utility problems.
please guide me if there is any solution that accepted to regulatory.
I agree with Dr. Rajeev, Please satte your problem clearly. You have discussed about two issues one Dr.Rajeev has answered. The second is if there break down in the equipment, you have to investigate the breakdwon mean wile shift the material to the stand by equipment. Also veriy that effect has on other samples also.
Thanks for the reply, i got the answer to my question.
but still have some doubts as follows,
1. If there is no additional sample for the stability study and the results of the respective interval is failing. can we use the sample quantity kept for the next frequency.
2. If not then what?
3. If in case there is no standby stability chember, then what?
4. if there is contineous alarms for the failure of chember conditions due to any of the reason (Water supply, electric supply, environmental condition in the area)
In addition to the answer given by Dr. Rajeev and Raghav, please go through the SOP on OOS/Breakdown in stability studies. If necessary revisit the Protocol. Some guidance can be obtained from "How to Do Document" given by fefic/APIC Ver. 5 Nov 2006. Please try to find the differnece between ca and continuous improvement. caPA - give more time for PA rather than doing ca.
Standby Stability Chamber is highly recommended.
If there is a continous failure of the equipment due to utility related issues, please do the ca first and more attention to PA.
Q . If there is no additional sample for the stability study and the results of the respective interval is failing. can we use the sample quantity kept for the next frequency.
A Study the root cause, production process, if necessary apply change control.
Hi, I think we should answer to Sunil's question, ie. if we observed negative result at one time point what is next? Can we use samples which is alloted for next time point?
I think using sample from next time point is possible. Otherwise we should have a set of sample back up to take care of this particular task.
When we design the stability program and calculate the sample requirement for the the entire stability program, we should keep sufficient samples including samples required for restest due to OOS or any significant difference occures with respect to the initial time point resutls. My recomendation is to store and pull additional samples every pull point to avoid the sample deficiency in case of OOS. Also, it is a good practice to maitain retain samples during each pull points which will help to solve the issues Mr Sunil has brought and it is a good laboratory practice too. We can always pull the additional samples from the chamber meant for next time points but the duration between the actual pull point and the additional pull date should not be morethan 2 weeks. There is no regulation to quote here but from the scientific point of view, the sample pull date should be close to the actual pull date.
If you are dealing with development stage stability studies, you have some freedom in pulling samples few weeks after the actual pull dates or from the next time points. If you are dealing with clinical or Phase III or registration stability studies, we need to approach the above issue very carefully because FDA inspectors can raise lot of red flags with your stability program if you are not keeping enough samples for retest or investigation etc.,
In my view all the method of analysis used for stability studies are validated methods.The followings questions are to be raised if studies goes out of OOS
1.During forced degradation studies( At all extremes) we will observe impurities occur during studies. is the OOS impurities are related to those impurities , If no then sample is contaminated.
2.The OOS impurities are compared with validation methods if the impurities are not related to known and un known impurities you can confirm that sample is contaminated.
3. In stability sample plan we take sample qty which is the double qty for one complete analysis, so in such case we can take next intervel sample and can be verified and officaily documented.
4.But i am not clear about regulatory requirement reference for taking next intervel sample, but any regulatory requirement refers actual documentation(Online) with proper Justifications and CAPA.
5.Comming to stabiliity chamber failure a CAPA to be taken and go through a predetermined schedule for preventive maintainance of the equipment with a stand by equipment for emergency.
If there is the electricity main supply problem continuously which leads to continuous interruptions in the stability study what to be done in this case.
The only solution (the best one too!) is to have a very good UPS system. I don't know whether your question is real or hypothetical (for discussion purpose). If it is real, study the interruption pattern, try to solve with the EB Engineer. If the problem is related to transformer (power distribution related due to load) attend to this and resolve this issue.
I wonder whether any guideline is available as an answer for your question.
Sunil if you want to perform real stability, then take necessary control measures as per the requirement.
As far as guidance document related to permissible interruption is concern , see ICH Q1A, Glossary , Storage condition tolerance
Storage condition tolerances “The acceptable variations in temperature and relative humidity of storage facilities for formal stability studies. The equipment should be capable of controlling the storage condition within the ranges defined in this guideline. The actual temperature and humidity (when controlled) should be monitored during stability storage. Short term spikes due to opening of doors of the storage facility are accepted as unavoidable. The effect of excursions due to equipment failure should be addressed, and reported if judged to affect stability results. Excursions that exceed the defined tolerances for more than 24 hours should be described in the study report and their effect assessed”
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