Method Revalidation?

[Rhodium]

Thanks in advance for any help with this question.

Would all/any of these changes made to a GC instrument require a method revalidation? (GMP environ.) If so, what extend of validation is recommended?

1).Switching from packed to capillary column.

2). Switching carrier gas from helium to hydrogen.

3). Switching from helium makeup gas to N2?

My guess would be any of these would require at least some revalidation, but I was hoping there may be a way around this.

[dblux_]

Thanks in advance for any help with this question.

Would all/any of these changes made to a GC instrument require a method revalidation? (GMP environ.) If so, what extend of validation is recommended?

1).Switching from packed to capillary column.

2). Switching carrier gas from helium to hydrogen.

3). Switching from helium makeup gas to N2?

My guess would be any of these would require at least some revalidation, but I was hoping there may be a way around this.

Agree with you. All these changes require revalidation.

[chromatographer1]

#1 Assume a complete revalidation is necessary.

#2 Same

#3 I would assume this change would increase the sensitivity of the FID if the flow was held constant. If this were checked for each analyte in your methods and no loss in sensitivity or linearity were noted little else need be revalidated (the carrier gas remains the same).

These opinions should be confirmed by your lab's regulatory authorities.

best wishes,

Rod

[Rhodium]

Thanks for the input. I feared revalidation was required for all these. From a chromatographer viewpoint, what exactly are the changes in 1,2, and 3 that would trigger the revalidation? Flow rates and sensitivity?

[dblux_]

Thanks for the input. I feared revalidation was required for all these. From a chromatographer viewpoint, what exactly are the changes in 1,2, and 3 that would trigger the revalidation? Flow rates and sensitivity?

IMHO
1) - 2) resolution
1) - 3) LOD, LOQ

[Consumer Products Guy]

I'm definitely NOT a cGMP expert. Most of what I've experienced over the decades is 99% interpretation.

That said: yes, must revalidate for #1 and #2.

As to #3, I "think" a big question is whether the validated test method even mentions what the make-up gas is. I'd say the cGMP test methods we use do not specify stuff like make up gas composition or amount, or even FID fuel and air flow levels.

I just checked USP 32 GC Method <611> for alcohol content; there is nothing in it about the FID gases at all. It does specify helium as carrier gas.

[lkochraney]

The real answer to this question should be directed to the QA/QC Officer of your company; however, for practical purpose, the answer is yes, especially for changes #1 and #2.

You will see a significant change in retention time, resolution, increased sensitivity, etc. when moving from a packed column to a capillary column, and if the phase is polar, possibly a change in elution order of the compounds.

Difference in retention time, resolution, and increased sensitivity is self-explanatory; however, change in elution order is not. It has to due to difference in the polarity of the phase at different temperatures and the different amount of phase coating from a packed column compared to a capillary column. There is no direct method of getting the same phase load on a capillary column converting from a packed column; therefore, the actual polarity may not be the same.

If using a polar phase, the phase polarity changes with changes in temperature. This is also true if there is a difference in flow rate, or for capillary columns, linear velocity. For example, if using a method published in a journal article or a manufacturer of capillary columns, and the flow rate or linear velocity you use is different from the article method, compounds will elute at a different temperature. As stated above, polarity of polar phases change with temperature, which can create elution order changes. This is one of the reasons that it is very important to use individual compound standards to set up and achieve optimum chromatographic conditions.

As for possibly doing a mini validation, I would suggest doing a completely new validation. Mini validations are typically used when changing from one brand of column to another, but still the same phase type and dimensions.

I hope this helps answer your questions, but again, you should check with your QA/QC Officer and the SOP for method validations.

Regards,
Linda Koch

[krickos]

Thanks in advance for any help with this question.

Would all/any of these changes made to a GC instrument require a method revalidation? (GMP environ.) If so, what extend of validation is recommended?

1).Switching from packed to capillary column.

2). Switching carrier gas from helium to hydrogen.

3). Switching from helium makeup gas to N2?

My input would be any of these would require at least some revalidation, but I was hoping there may be a way around this.

The most intriging question is perhaps the amount of revalidation would be needed, depending on which of the above is done.

1. Big change (same phase or not?) most revalidation I would assume.
2. Signifacant change but really as big as 1?
3. Would typically improve sensitivity, limited revalidation?

Not all to easy depending on policy in companies and type of change.

[chromatographer1]

krickos wrote:

"The most intriging question is perhaps the amount of revalidation would be needed, depending on which of the above is done.

1. Big change (same phase or not?) most revalidation I would assume.
2. Signifacant change but really as big as 1?
3. Would typically improve sensitivity, limited revalidation?

Not all to easy depending on policy in companies and type of change."

1. Absolutely a complete revalidation.
2. You are right, not as big, but big enough to have so many possible complications that a complete revalidation is the safest bet.
3. As long as there is not enough improvement to affect LOD and LOQ and it shows no reduced sensitivity (remember, anything is possible unless it is shown NOT to be possible) very little additional work should be required. But a wise chemist who wants to keep his job and stay out of jail would demonstrate that a change to N2 would not cause any linearity or sensitivity issues.

best wishes,

Rod

[Rhodium]

I appreciate all the input- thanks guys

[Yama001]

Just a note - I have seen elution order changes when switching from Helium to Hydrogen carrier - no doubt some interesting physical chemistry going on there.

[Johnny Rod]

I would agree with Rod, for 1 and 2 these are big changes which can affect most or all areas of the analysis. with regard to 3, look at the table in ICHQ2. If it is an analysis for impurities then yes LOD/LOQ are needed to be examined, if it's an assay then no. You might want to consider linearity and range though, in either case.

Do you do regular PQ/PV/whatever you call it? If so (and you would do so after making the change on the instrument) and this shows linearity etc. is unaffected then you may get away with not doing it in revalidation in the case of 3.