validation

[upamaniah]

Dear All,
In lc analytical method validation - robustness - mobile phase composition variation does only organic composition shall be varried such as
As per STP buffer:400mL and Acetonitrile:600mL
Variation-01(110%) buffer:400mL and Acetonitrile:660mL
Variation-01(90%) buffer:400mL and Acetonitrile:540mL.

or do we have to perform for buffer composition also.
please calrify.
related to this quiery, any publication, article or guidelines are available
thanks and regards
vijay

[Uwe Neue]

If indeed your method requires a buffer, you need to include its pH and its concentration in the robustness protocol.

[gbalock]

Vijay,
Are you are asking about buffer concentration? If so, and you believe that buffer concentrrration has an impact on separation, then you should do it. If you don't think that it has an impact on seperation, then don't.
George

[Consumer Products Guy]

gbalock - my company QA would require the entire validation to be repeated from scratch because you mis-spelled "separation" the second time, and you mis-spelled "concentration". They's also make me start over because I used a hyphen in "mis-spelled". It's so good for my company to have such a dedicated QA department....

As to the subject, I'd say that one must demonstrate and document that reasonable changes in buffer do NOT affect the results (otherwise, how would you know? For example, when we used 0.4% phosphoric acid in the aqueous phase, we also assayed the same sample using 0.3% and 0.5% phosphoric, each a whopping 25% change in acid content.

[tom jupille]

There is an interesting attachment (Attachment A) in FDA document ORA-LAB.5.4.5 ( http://www.fda.gov/ora/science_ref/lm/v ... _04_05.pdf ) which suggests default adjustment limits on LC conditions. That allows a 10% variation in buffer or salt concentration. At a minimum you should establish that this variation poses no problem (whether you need to fold this into the robustness part of the validation or whether you can simply refer to experimental data obtained during method development is a matter of your SOPs).

If you set tighter limits, you will probably be asked justify them with more rigorous robustness testing.

[Consumer Products Guy]

Tom - I've recently printed and shown FDA document ORA-LAB.5.4.5 including the attachments to our famous QA department (of which I'm not a member), and have gotten some concessions for a current validation project (the first one they've ever stuck their noses into, and insisted we validate the existing USP procedure because we don't make the active-just the finished dosage form). But my QA seems reluctant most times to accept the written FDA word, especially if that word doesn't agree with their pointyhaired boss'. Interestingly, though: my QA seems to pick and choose certain aspects of cGMP to follow, and ignores others......my new boss just says to do what they want, they're paying......I need to write a book someday....just submitted were 4 four-month freeze-thaw samples (all same lot) - all had leaked, and there were no control/ambient samples, so how will anyone know if any active loss is from freeze-thaw or from aging (they looked around yesterday, couldn't find any samples from that lot anywhere to use as a control)? Too bad they didn't spend time on a two-minute phone call to me four months ago or they could have had an ambient control sample...the QA arrogance here is beyond belief, like they never feel they need to ask for anyone's opinion or help.

[jtreacy]

I get the feeling Consumer Products Guy doesn't like QA people for some reason??

[WK]

CPG - the pointy haired boss is in Dilbert right?
Have QA been issued with laptops by yourself?! Maybe you can shake to reboot them!

[Consumer Products Guy]

jtreacy - I'd like our QA if:
they knew what they were doing
they knew the cGMP regulations and documents
they were willing to listen
they were willing to compromise
they stayed at same lower price range hotels as others
they didn't inflate their travel reimbursements
they didn't have an ear to the VP because they sure get staffing
they didn't bury (immediately) all their mistakes
they actually walked into the QC lab at Manufacturing to take a look, instead of just looking at documents

WK - of course QA all has laptops, how else could they surf the Internet while at Manufacturing? My department does not have laptops.

[WK]

CPG,
Dilbert issued his pointy-haired boss an etch-a-sketch and made out it was his new lap-top. So when pointy-haired boss complained it had crashed he came in and showed him the re-boot routine (shake,shake..)!!
WK

[MIB_EO]

"actually walked into the QC lab at Manufacturing to take a look, instead of just looking at documents "

The downfall of all QC depts anywhere. It is an EASY trap to fall into. Having previously been the QC dept for a while. In the various ISO "Quality STandards" there is very little actual requirements for written records. A few, but not that many. However if you write a procedure stating that this must be recorded, then it must. And then QC write a checklist to record that it has been recorded. And very quickly QC becomes a matter of huge manuals detailing every little step and checking paperwork rather than real results. However once established it is very hard to get rid of.

Try an effeciancy audit - does this manual and this step and these people and those procedures reduce the cost/time of the product (including product recalls)?

[jtreacy]

QA and the like are populated by failed or poor scientists in general.

The 'thick' one from your college is usually to be seen driving around in a huge BMW and is QA or "Stop Things Happening' manager somewhere.

It is indeed an unfair world!

Don't get me on to health and safety people though. They make the QA guys look like visionaries!

[Russ]

Our QC department used to test samples of products made for us by other companies using our formulations. They were having problems getting acceptable assays for some of the products; some were less than 50 % of what they should have been. The VP QA at that time was concerned that if we knew there was a problem, we needed to do something to fix it. The solution? Some of you may have already guessed it. The QC lab was told by the VP QA to quit testing the samples from that supplier! I am not making this up. My imagination is not that vivid.

[upamaniah]

i didn't get the reply.
i am not talking about variation of buffer concentration, but buffer volume presents in the total mobile phase composition. i hope buffer concentration should not be changed at any cast because it is an integral part of the method of analysis.
vijay

[Uwe Neue]

Vijay: You did get an answer. If your method requires a buffer, you will need to change the buffer concentration as well as the pH. Simply changing the buffer volume in the mobile phase (i.e. changing the ratio of buffer to total solvent) is not enough.