Expectation for sterile fill vial weight check data

[PaladinMike]

Hello all.
Looking for information regarding industry standards for weight check data obtained during filling from the filling machine itself. Not related to in-process QC checks during filling....

1) Is there an expectation (FDA or other reg body) that the data file from the filling machine capture the fill weight of every vial during a batch?
2) And then is the captured data reviewed, trended, etc. in some standard manner to be included in the batch documentation?

I have a client that is considering 'speeding up' the filling process by reducing the check weight to every 3rd or 5th vial...want to advise them properly of the merits or risks of that change. Personally, I think if every vial can be monitored/recorded, it should be, but they are reporting that the overall impact on filling time could be 1-2 hrs over the batch filling time. And I did do a quick review on the FDA Guidance for Sterile Drug Products and don't see a specific answer to the question, other than it should be part of the filling and media fill processes.

Thank you for your suggestions

 

[indubioush]

Was process validation done? https://www.fda.gov/files/drugs/published/Process-Validation--General-Principles-and-Practices.pdf

 

[PaladinMike]

That was the initial intent of the 3x media fills that the client performed to qualify the filling equipment and process. Initial expectation was to perform the media fill and collect all data, including fill weight data, to establish all the various tolerances and validation parameters needed. During the first run they made a decision to speed up the filling process by reducing the check-weigh monitoring to every 5th bottle which reduced their fill time by about 1.5 hrs, meeting their planned expectations regarding fill time, settle plate media exposure, etc. Being off site, I wasn't made aware of the change until after the three media fills were done over three successive days and had started reviewing the data from the unit and found the change in the data acquisition. So while we have some data regarding the fill weight accuracy, it was a deviation on the media fill that they are documenting.
My ask is how to proceed from here. They are adamant that they can't go back to check-weigh on 100% of the vials as the run will take too long and cause other issues that they don't want to experience. My experience in sterile vial filling is to have the check-weight info on 100% of the vials and allow the machine and the established tolerances to perform any needed individual vial rejections based on fill weight. I need more evidence and industry practices to try and convince the client to reduce the batch size and allow for 100% vial weight check and meet their 8 hr fill timing, as I don't feel confident that the regulatory agencies will allow for them to proceed as they want.
Any and all help welcomed on this.

Mike

 

[indubioush]

Are you following this guidance: https://www.fda.gov/media/71026/download
The purpose of process validation is to have assurance the process consistently produces product that meets specifications. If you are 100% verifying, there is no point to process validation.
If changes were made during process validation, the process validation activities that have been negated by the change need to be repeated.

Process control tests are used to confirm the state of control. The sampling plan for this should be based on risk. However, if process validation of a process is done, and the results are acceptable, 100% verification is not required and doesn't make sense.

 

[PaladinMike]

Good morning, and than you Indubioush....I completely understand and I am working with the client to perform a full process validation. However my question from the original post still stands....if the machine is capable of check weigh of each vial, is there an expectation from regulatory bodies to utilize that functionality 100%?

Thank you.

 

[indubioush]

If process validation has been completed, the FDA is not going to require a 100% verification. They will require that statistical techniques and consideration of risk were used in determining the data collection plan for process monitoring.

You have not completed process validation. You need to have a process validation plan and be working under those protocols at this time.

 

[PaladinMike]

Thank you.