Working standard qualification


let me give some background.

we have been using USP method to quality working standard(In-house standard).

we qualify In-house working standard against Referance standard. the following test is performed.

1) ID 2) Assay 3) Water/LOD 4) Appearance

I have following question.

1) Does any one know required method validation parameters for Assay working standard qualification of API?

2) Assay working standard method - Forced degradation required?

3) I know there is FDA GMP stage II guidence which recommend that no need to perform forced degradation if sample is available at expiry period. sample may be injected to check the peak purity and based on that it is proven that degradant is seperated from the main peak and peak is pure. Now i want to know is this a right approach? see below link

Let me clarify that we make OTC products and it is not for filing purpose.


Replies to this Topic


Its required ,

 if you are not a manufcacturer of the perticular API (which is your working std). ask  the vendor to get the report of forced degradation and validation study,



only two parameters, Specificity and precision is enough for method validation as a part of method verification.


Forced degradation is required  only when  you are the manufacturer of the API, because API root of synthesis is different from one manufacturer to another manufacturer.

If you are not the manufacturer , get the details from the vendor , in this case only assay validation is required. forced degradation is not required.


of course , the approach is right, but you have no evidence that the expiry evaluated by the anlytical method should be stabilty indicating(forced degradation passed).

Any method which is not evaluated forced degradation study is not suitable for stability assessment like retest or expiry.

Forced degradation study is a verification of anlaytical method only.

you have one more option : check the peak purity for the last interval sample which is incubated at the stability chamber .


Bujji Kanchi.




I hope I'm not gonna derail this thread, but how do you qualify a working standard if the assay is by titration ?

the working standard qualification is done to the material.

Analytical method valiation and forced degradation done to analytical method.

Any analytical method must be validated.

Working std qualification procedure

Analyse the your inhouse material in triplicate assay, take the average assay value.

1.If it is titrimetry, assay it directly as per STP(TEST PROCEDURE)

Identification against USP standard.  test for MC/LOD

2.If it is by LC/GC, assay it against the USP standard

Identification against USP standard.test for MC/LOD.


Bujji Kanchi.

That was my reasoning too.

Why only 3 repeats though ? If for validation one needs six repeats for some parameters (and 2 analysts) is just 3 repeats enough for the working standard ?

Is there a specific guideline dealing with this subject ? 

thanks ~lucian

That is your choice. No guideline  specifiying six replicates in case working standard qualification, each organisation has their own sop.

if you want to repeat six times. you can do .


Please remember that, you are qualifying a working standard on a validated method.

Treat method validation is different concept from working standrd qualification.

Few of the organisations are doing six replicates while carrying out working stadnard qualification.

Actually I do not understand your concern exactly ?

ICH Methodology Q2 is specifying six replicate determination of precision study

why you are relating the precision study with working standard qualification.

Any way you got the answer. I hope.

please write for any further clarifaction

Thank you very much.

Best regards,

Bujji kanchi.


Thank you very much Bujji. One of my concerns, was that I wanted to validate a method using an working standard. (We are required to validate all methods even if we're using well established pharmacopoeia methods). And I was thinking that my working standard had to be characterized better than any other validation parameters (precision for example).

I'm assuming you are using a primary standard to validate a method and then use that method to characterize the secondary standard.

So if I wanted to validate a titrimetric method which has no CRS standard, I would have to characterize a standard first and then use the standard to validate the method. It seems a circular problem for me so here I am with my many questions.

thanks you very much



I am very happy to discuss with your approaches.

Any material which has characterised and assayed can be a CRS.

In this case you characterise your material(which you have plenty of Raw material, take a batch and characterise it)

Once it is characterised, It will be your CRS(IN-HOUSE), This will be used instead of ws.

If the method is pharmacopial, and CRS is available, first we qualify working standard , then method validation will be done(Method verification as per USP <1226> General chapter, only specificity and Precision is verified)

If the method is pharmacopial, Where CRS is not available, we prepare Primary std by characterising it. then validation, no working stnd preparation. primary will be used as working std.

can you call me , if you have time. so that we will discuss further about this.


Bujji Kanchi.


CRS has additional tests like NMR, UV,IR, Mass along with the Battery of tests(STP).

Where as working std does not require all this.

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