Method transfer in a GMP lab

[GT]

Hy,
I need to transfer a full validated HPLC purity method for Active Pharmaceutical Ingredient from an old models of HPLC to a new models.
Which are the paremters I have to revalidate (ex. precision, LOD for all know impurities...) ?
Any suggest will be appreciate.

[tom jupille]

If the original method did not specify the brand and model of HPLC, I believe that no revalidation is required so long as you meet the system suitability test requirements.

[pochengjean]

If the original method did not specify the brand and model of HPLC, I believe that no revalidation is required so long as you meet the system suitability test requirements.

hmm...according to the FDA requirements, I think you are required to perform a validation on your own sets of system unless the clients specified.

[Consumer Products Guy]

Our cGMP test procedures do not specify an instrument manufacturer or model. Similarly, our pure solvents are listed as HPLC grade. We do (obviously) specify the column completely, including its Supplier name and part number, and same for any gusrd column used. So I agree with Tom, no need to do anything special for a new(er) HPLC.

[tom jupille]

hmm...according to the FDA requirements, I think you are required to perform a validation on your own sets of system unless the clients specified.

Actually, if you can point me to a reference for that requirement, I'd be grateful. My interpretation has always been that transferrability is what system suitability is all about. To quote from a current FDA draft document:

• "Each analytical procedure submitted should include an appropriate number of system suitability tests defining the critical characteristics of that system." (italics mine) http://www.fda.gov/cder/guidance/2396dft.htm#XI

Basically, if your system meets the system suitability test(s), it is suitable for the analysis.

[MK]

we've done few transfer studies from a contract lab where the methods were developed. we wrote a short protocol including SST and analysis of few samples which were analysed earlier in the original lab. All kinds of problems may appear even on transfer between very similar equipments. For example we needed to change the injection volume on transfer from binary pump to a quat. pump due to terrible peak fronting. Therefore we repeated LOD and LOQ.

However, a good SST would include a precision, tailing, control sample, LOQ/D solution etc. I agree SST could be enough if it's correctly set up.

[pochengjean]

hmm...according to the FDA requirements, I think you are required to perform a validation on your own sets of system unless the clients specified.

Actually, if you can point me to a reference for that requirement, I'd be grateful. My interpretation has always been that transferrability is what system suitability is all about. To quote from a current FDA draft document:

• "Each analytical procedure submitted should include an appropriate number of system suitability tests defining the critical characteristics of that system." (italics mine) http://www.fda.gov/cder/guidance/2396dft.htm#XI

Basically, if your system meets the system suitability test(s), it is suitable for the analysis.

hm...the way I read it is that the system suitability has to be within criteria in order for the data result to be valid, provided by the fact that the full system validation or partial validation was done by the user or developer. Therefore, the user laboratory should always perform at least partial validation (if stability test is established, then the stability test might not be required...etc) according to (http://www.fda.gov/cder/guidance/cmc3.pdf). I can be wrong.

Anyway, I always advise the clients to perform at least the partial validation to avoid the trouble from the auditor.

"Methods validation should not be a one-time situation to fulfil Agency filing
requirements, but the methods should be validated and also designed by the developer or user to ensure ruggedness or robustness. Methods should be reproducible when used by other analysts, on other equivalent equipment, on other days or locations, and throughout the life of the drug product. Data that are generated for acceptance, release, stability, or pharmacokinetics will only be trustworthy if the methods used to generate the data are reliable. The process of validation and method design also
should be early in the development cycle before important data are enerated. Validation should be on-going in the form of re-validation with method changes."

[adam]

As someone who has worked in the Pharmaceutical industry for some time, I defenitely agree that full re-validation would be overkill here. The industry standard approach, when transferring a method to another lab, is to perform a method transfer. And this generally consists of a compararive accuracy study: meaning that some lots would be run at both labs and the results must agree within certain predefined acceptance criteria. You also should re-determine the LOD/LOQ because this is instrument dependent.

Adam

[tom jupille]

Anyway, I always advise the clients to perform at least the partial validation to avoid the trouble from the auditor.

I won't argue with that statement at all!

I think we're responding to different interpretations of the original post, which (in my reading) didn't say anything about transfering to a client or a different lab, merely to a newer instrument. In that scenario (new instrument, same lab), I really don't see a regulatory requirement for revalidation (again, assuming the new instrument meets the SS, and that the SS is meaningful; i.e., the method was properly validated to begin with).