Analytical method and Method validation question-Linearity

GOOD VALIDATION PRACTICE (cGVP) LABORATORY, METHOD AND ANALYTICAL VALIDATION
1

Hi,
I am in the process of creating an analytical method for the technicians to run following a USP 36 monograph. The steps i have taken are

Developing the method on to hard copy with slight changes to the column .The API is Minoxidil.
Validating the method

Now the QA has come back and updated the method requesting linearity run for every time the Assay is done . Now my question is, since we have already implemented this in the method validation , is this still required in an assay after the fact?

In my years of practice i have not seen this and the new QA is requesting this. adding this can not only add cost to the test but also time. USP 36 only specifies System Suitability with requirements of a resolution and a relative standard deviation but no linearity.
Please let me know your thoughts on this.

2

[quote=pidluk]Hi,
I am in the process of creating an analytical method for the technicians to run following a USP 36 monograph. The steps i have taken are

Developing the method on to hard copy with slight changes to the column .The API is Minoxidil.
Validating the method
…[/quote]

Assuming you are running a typical assay with one level of standard and sample concentrations, if the method did not require running linearity every time, you don’t have to do it. Even if you do, what is the use of it? There is no system suitability requirement or use of linearity data in assay calculation. Ask QA the reason for doing it. Thanks.

3

[quote=pidluk]Hi,
I am in the process of creating an analytical method for the technicians to run following a USP 36 monograph. The steps i have taken are

Developing the method on to hard copy with slight changes to the column .The API is Minoxidil.
Validating the method

Now the QA has come back and updated the method requesting linearity run for every time the Assay is done . Now my question is, since we have already implemented this in the method validation , is this still required in an assay after the fact?

In my years of practice i have not seen this and the new QA is requesting this. adding this can not only add cost to the test but also time. USP 36 only specifies System Suitability with requirements of a resolution and a relative standard deviation but no linearity.
Please let me know your thoughts on this.[/quote]

Not Required.

For every activity, there is a purpose.

Simply, assessing linearity without any reason doesn’t make any sense.

And no where it is written to do that.

as per USP <621>, chromatographic chages are acceptable to achieve the system suitability.

as per USP <1226> The suitability of the method should be verified for the intended use.

In this(1226) Linearity is not given, Of-course.

The purpose of the parameter linearity is introduced to verify the beer’s law[absorbance is proportional to concentration].
Even it is done in validation, why everytime the linearity is required.

No where in the world is doing this, I hope…

Ask your QA to show the reference guide or SOP for this. They might be fainted.

Regards,
Bujji Reddy Kanchi.
9676749937.

4

The reply given was :
Reason #1) Due to the fact that we are running different tests of different products and the fact that we are only testing this product maybe 3 times a year hence the linearity needs to be tested to prove there is no deviance in curves.
Reason # 2 , since we are not a testing lab but a manufacturing facility with the above given reasons.

My argument was we are not making injections but a topical with a single concentration of 2 % API and a single RM API.
Suitability requirements set by USP 36 Page 4378 for minoxidil is already set for resolution NLT 2.0 between the internal standard and minoxidil
Relative standard deviation NMT 2% from NLT four replicates.
So my question to the forum is what benefit will linearity serve? What will it prove? Is there really a need ?

5

[quote=pidluk]The reply given was :
Reason #1) Due to the fact that we are running different tests of different products and the fact that we are only testing this product maybe 3 times a year hence the linearity needs to be tested to prove there is no deviance in curves.
Reason # 2 , since we are not a testing lab but a manufacturing facility with the above given reasons.

My argument was we are not making injections but a topical with a single concentration of 2 % API and a single RM API.
Suitability requirements set by USP 36 Page 4378 for minoxidil is already set for resolution NLT 2.0 between the internal standard and minoxidil
Relative standard deviation NMT 2% from NLT four replicates.
So my question to the forum is what benefit will linearity serve? What will it prove? Is there really a need ?[/quote].

you do one thing…

do whatever QA says. Close the Issue. so that you will be fine.

The answer for your question is : Linearity is not required in you case.

Regards,
BR
9676749937

6

[quote=bujjikanchi].

you do one thing…

do whatever QA says. Close the Issue. so that you will be fine.

The answer for your question is : Linearity is not required in you case.

Regards,
BR
9676749937[/quote]

hi, validation proves that the method is consistent in all parameters including linearity. Once validation is compleated, no need repeat the same for all the tests.

7

[quote=pidluk]The reply given was :
Reason #1) Due to the fact that we are running different tests of different products and the fact that we are only testing this product maybe 3 times a year hence the linearity needs to be tested to prove there is no deviance in curves.
Reason # 2 , since we are not a testing lab but a manufacturing facility with the above given reasons.

My argument was we are not making injections but a topical with a single concentration of 2 % API and a single RM API.
Suitability requirements set by USP 36 Page 4378 for minoxidil is already set for resolution NLT 2.0 between the internal standard and minoxidil
Relative standard deviation NMT 2% from NLT four replicates.
So my question to the forum is what benefit will linearity serve? What will it prove? Is there really a need ?[/quote]

Linearity can be beneficial when testing samples infrequently because it confirms a concentration range above and below your target standard value. You can achieve linearity via injection volume as oppose to preparing several standards at different concentration especially since it’s a USP method and the linearity was confirmed during USP validation. It’s important that you maintain a good slope and R squared value for your linearity so that your sample concentration result falls on that line every time. Maybe your QA will except a linearity via injection volume.

8

[quote=pidluk]The reply given was :
Reason #1) Due to the fact that we are running different tests of different products and the fact that we are only testing this product maybe 3 times a year hence the linearity needs to be tested to prove there is no deviance in curves.
Reason # 2 , since we are not a testing lab but a manufacturing facility with the above given reasons.

My argument was we are not making injections but a topical with a single concentration of 2 % API and a single RM API.
Suitability requirements set by USP 36 Page 4378 for minoxidil is already set for resolution NLT 2.0 between the internal standard and minoxidil
Relative standard deviation NMT 2% from NLT four replicates.
So my question to the forum is what benefit will linearity serve? What will it prove? Is there really a need ?[/quote]

Hi there,

Presumably you prepare duplicate standard solutions one used as a check standard for the other. Could you not prepare two standards solutions with concentrations that bracket your expected result, force calibration through zero and use that as your linearity check.

Incidentally I do not understand your QA reason #2. Presumably you are a testing laboratory within a manufacturing facility, the GMP requirements are the same irrespective of the facility.

Regards

David