Doubts regarding IS variation, ISR failure & SEL/SPE Acceptance criteria [Regulatives / Guidelines]

posted by ElMaestro  – Denmark, 2021-05-12 09:10 (168 d 03:26 ago) – Posting: # 22342
Views: 805

(edited by ElMaestro on 2021-05-12 12:48)

Hello Rams,

(typo in my first post, edited)

how right you are when you say that information is wealth. :-)
On the very general level I am kind of trying not to ask questions starting with "Why" or words to this effect, when it comes to guidelines and guidances. Though we have FOI acts and public consultations and symposia with regulatory attendance, the true answers to the questions starting with "Why" are not often in the public domain.

» 1) Why we are fixing IS variation range ±50% from the average IS response of accepted CCs &
» QCs. (while using a dutrated IS why we not keeping ±15% or ±20% or some other range).

I don't know why you or your company follows this practice. Ask internally.:-D
There is no requirement to follow exactly this rule, and you are free to decide on rules that make more sense.
±50% is common, ±80% is not unusual. Both may be acceptable.
Lots of it may be equipment-dependent and it is always a bit analyte and IS-dependent, too. So, sometimes you need an assay-specific rule for IS-variation rather than a system-wide rule.

» 2) If in one project ISR failure observed frequently/continuesly means what will go to next
» actions and please give some exaples with clarification for the reasons for those
» failures.

Scenario: When you fail, investigate. If no root cause (which is most comm,on) perhaps you can re-inject or re-extract once. If failing again and there was no root cause, the method may not be good. A run failed and a run passed should be assessed with caution. Discuss. Make very clear on source why the passing run was a more true reflection of assay performance than the failing run.
Variations in internal voltage, static phenomena, matrix effect, there are all sorts of weird things that can affect your IS variation, many of which you have no way of knowing when investigating.

» 3) As per new guideline in Selectivity and Specificity for analyte interference in blank
» samples were comparing with the speific lot LLOQ response (Which lot used for BLK & LLOQ
» Preparation) but why the ISTD response of the balnk samples were comparing with the
» average response of accepted CCs & QCs why not comparing with respective LLOQ ISTD
» response.Please clarify.

The rhetorical answer must be that this approach is suggested in FDA's guideline e.g. Table 1.
Why FDA wrote their propposal that way, I have no idea, see above. When I write "I have no idea" it does not mean "I disagree" or "I agree". It just means "I have no idea" as I was not following these discussions so closely and I would not have been privy to the true reason anyway.

Pass or fail!
ElMaestro

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