Regulatory requirements

[marinacohen11111]

Dear Forum,
We are pharmaceutical company (new) that starts preparing to FDA inspections.
We have consulted regarding certain HPLC topics and I wanted to ask if they are usually performed in FDA regulated pharmaceutical companies:
1) We perform system suitability test at the beginning of the work (system suitability solution, control standard preparation, standard repeatability (5 or 6 injections) and then standard every 6 samples or after 3 hours and the end. We were consulted that FDA requires performing all the initial system suitability tests (including 5 standard injections) also at the end of work and in the middle of the work, if it takes more than 8 hours.

2) Empower 2 is not FDA compliant, and we have to switch at least to Empower 3.

3) When we switch to Empower 3, we would have to revalidate all the methods.

Please advise, if FDA regulated lab should act according to all this requirements?

If revalidation is really required, is it full revalidation? Including stability indicating and all?

Thank you very much!

[Blazer]

1) I've never been told by an inspector or auditor that you need to perform full system suitability in the middle and at the end of an HPLC analysis. Some sort of check at the end is important to ensure that your system hasn't drifted during the analysis. A check in the middle of the sequence can be considered a good business practice if the run time is long and you have a lot of samples.

2) Empower 2 is just as compliant as Empower 3. That said, it could be that the consultant found issues with your IQ/OQ/PQ or found that you're having issues with the audit trails (as examples). But other than something like that, I know of no reason why Empower 2 is considered non-compliant and Empower 3 is considered compliant. I've worked with many places in the past several years that have one or the other and all of those places have been found to be in compliance by FDA/EMA.

3) Changing from Empower 2 to Empower 3 will not require you to re-validate your methods.

In sum, without knowing the details of the consultant's exact wording and concerns, I think the advice you've gotten from this consultant is all wrong.

[marinacohen11111]

Thank you very much for the reply, may be requirements for oversea companies are stricter?
Other people working in FDA regulated labs agree?

[marinacohen11111]

Please, it will be very helpful if more people can comment!
Thank you!

[Consumer Products Guy]

1) I've never been told by an inspector or auditor that you need to perform full system suitability in the middle and at the end of an HPLC analysis. Some sort of check at the end is important to ensure that your system hasn't drifted during the analysis. A check in the middle of the sequence can be considered a good business practice if the run time is long and you have a lot of samples.

Agree. We did an initial SS of 5 injections, then an injection at the end and did an overall SS. If we had more than 10 samples, the overall SS was done using a standard injection after every 10 samples.

We typically injected every sample twice.

3) Changing from Empower 2 to Empower 3 will not require you to re-validate your methods.

It's the chemistry of the method that has been validated, and confirmed to be legitimate. Not the software package. For example, a test method validated on Agilent at R&D would not need to be re-validated using a Waters instrument, or at a different location like at manufacturing.

[DR]

Moving from Empower 2 to Empower 3 is pretty much a complete de-installation of the old and installation of the new software. As a result, you will have to repeat I/O/PQ on your servers, LACEs and any Citrix stacks. This is probably the "revalidation" that was mentioned.

Clearly, you're getting some bad information. You will have to figure out why and make some changes.