Qualification of working standards

Dear Friends,


I've a query regarding the qualification of secondary reference standard or working standard.

• Is it mandatory to use the reference standard of pharmacopeial standard like supplied by BPCRS, EPCRS & USPRS only for qualification of working standard to be used in routine analysis?

• Can we use a primary standard(A standard having the complete characterization like assay, related substance, mass spectroscopy, NMR, XRD) supplied by the API manufacturers for preparation of working standard to be used in routine analysis?

Secondly, we are qualifying the working standards against reference standard for one year as validity. can we do the same for two year validity?

 

Replies to this Topic

It is not mandatory to use reference standard of Pharmacopeial, we can also use a primary std. supplied by the other sources (well characterized ) but the source should be validated against reference standard. Substituting without supporting data is not acceptable.

 

 

 

based on sound reasoning and knowledge of how the material has been stored, you can decide the validity......

 

Thanks Anshul,

You mean to say the whatever the primary standard id supplied by the API manufacturer requires a back data that the primary standard is evaluated against a pharmacopoeial reference standard.

 

Secondly can we have the working standard qualified for a validity of 2 years.

Saleem,

you must place your standard into your stability program.  If you synthesize your primary standard and characterize, I recommend a 6 month retest period.  Once you completely characterize and qualify a primary standard, then you can assign an expiry date.  I hope this helps.  

Hi Saleem,

Is it mandatory to use the reference standard of pharmacopeial standard like supplied by BPCRS, EPCRS & USPRS only for qualification of working standard to be used in routine analysis?

Its not mandatory...

All oraganizations may not be able to  procure pharmacopeial reference standards due to price matters and other reasons.

Practically even those reference standards also well characterized and have proven scientific data .

Can we use a primary standard(A standard having the complete characterization like assay, related substance, mass spectroscopy, NMR, XRD) supplied by the API manufacturers for preparation of working standard to be used in routine analysis?

Yesss.....If you are using the pharmacopeial reference standard which is fully characterized, why not from manufacturer if i am right.

Additionally ask them to provide data if required.

Secondly, we are qualifying the working standards against reference standard for one year as validity. can we do the same for two year validity?

Validity of the working standard purely depends on stability of the API.

As courtland say have stability program by giving 6 months validity as initial.

You can not go for two year validity without any scientific data.

Finally you can recertify your working standard.

 

Regards

Satya,

In case If i have 2 years stability data for my API, can i assign 2 years validity for the working standard.

If your answer is yes, then why most of the manufacturers  will keep only 1 year validity?

regards,

Hi Rama,

I have products having 5 years retest and 4 years like that.

Based on above i can not give 4 or 5 years validity for working standard.

As per ICH or based on R&D supporting data we can give 6 months (not more than that) retest or validity period.

If you have sufficinet stability data (Not less than  two years) then we can go up to  one or two years validity,and this varies orgnization to organization.Suppose we are giving two years as validity for working standard which is having more than two years stability data.

We better to have working standard validity as 2 or 1 after that take a new lot for evaluation .If you dont have new lot recertify the same and reassign validity period.

Note: Recertification assined validity period should not exceed original retest period of API.

Hope got the answer

Regards

Dear friends

               As per ICH guidelines working standard  should be periodically requalified in accordance with a written protocol. And if you have stability data for long term upto 36 months or more than 36 months, You can give retest up to 36 months. Even though you have stability data more than that(36 monts)  extrapolation of retest is not accepted. So you maximum retest is 36 months (3 yrs)

People will give retest up to 36 months based on their product experience. Some people will give 6 months , some other 1 yrs and some other 2 yrs. What ever it may be you should prepare protocol for that.

Thanks Satya, i will agree with you..

 

Generally every body follow a maximum of 12 months validity even though they have 36 months longterm stability data for being safe side. But we can go upto 36 months based on ICH. No auditor will question you on that.

Actual scenorio is

If you dont have stability data - 6 months validity

9 months LT stability data - 18 months validity

12 months LT stability data- 24 months validity

18 months LT stability data- 30 months validity

24 months LT stability data- 36 months validity

36 months or more LT stability data- 36 months validity

After that no extrapolation of retest.

Above are few examples listed from ICH. Based on your stability data(LT,ACC,Intermesdiate) You can assign validity.

 

Dear Friends 

 

Pls. find below the mail trail for the query of reference standards by MHRA.


Dear Saleem Jawed

I have annotated your email with my replies.

I hope that this helps

Regards

Maria Barrett
Senior Pharmacopoeial Scientist
British Pharmacopoeia Secretariat
MHRA
Buckingham Palace Road, London, SW1W 9SZ, UK
Telephone: 020 3080 6555
Email: maria.barrett@mhra.gsi.gov.uk
Stay connected: mhra.gov.uk/stayconnected
MHRA is a centre of the Medicines and Healthcare Products Regulatory Agency

________________________________________
From: Saleem Jawed- Manager QC [mailto:saleem.jawed@optimusgenerics.com]
Sent: 10 September 2013 08:06
To: Barrett, Maria
Cc: Holland, Dr Patience
Subject: RE: Enquiry from the BP Website
Dear Maria Barrett,

Thanks for reply and support for understanding the issue.

Here are some specific query where I need your suggestions.

1. For API's, where the assay is carried out by titration,

a) No reference standard required for assay quantification?
That is correct.


 b) For identification by IR we require the reference standard, in that case can we use the BP reference spectra as reference?
The first time you carry out the test you should use the EP reference standard. For further tests you may use the reference spectrum that you have run.


 c) If BP does not have the reference spectra then can we use the IR spectra given in DMF of the API?

If the BP has a different means of identification then you should use these tests. If the IR of the BPCRS is concordant with the API then this may be used .


 d) We are doing Identification and assay as critical test for qualification of secondary reference standard or working standard. Can you suggest what are the critical test parameter to be carried out while qualifying a working standard and do give me some reference also.
This will depend on the use of the standard. When qualifying a secondary standard you would carry out the tests where the BPCRS is used. (Supplementary Chapter SC IV M reference standards) A secondary standard should exhibit the same property or properties as the primary standard, relevant for the test(s) for which it is established. The extent of testing is not so great as is required for the establishment of a primary standard. The secondary standard is established by comparison with the primary standard to which it is traceable. An official primary standard is used wherever possible for establishment of secondary standards.


2. Secondly as you reverted that we can use the In-house reference standard(previously validated with primary reference standard, like EPCRS, BPCRS or USPRS).

a) Suppose "X" API(Having expiry period of 3 years) is validated against current lot of BPCRS. The "X" API is also characterized. Now we can use the "X" API for working standard qualification. Can we "X" API for continuous 3 years as reference standard for qualifying the secondary reference standard?
When you purchase a BPCRS it must be used within 3 months of purchase. Your API may have an expiry period of 3 years but is it stored in exactly the same way as the reference standard? The BP cannot recommend how long you may use your secondary standard it. You will have to be able to provide documentation that it is suitable for use.

Warm Regards,

Saleem Jawed

From: Barrett, Maria [mailto:Maria.Barrett@mhra.gsi.gov.uk]
Sent: Monday, September 02, 2013 3:10 PM
To: Saleem Jawed- Manager QC
Cc: Holland, Dr Patience
Subject: RE: Enquiry from the BP Website

Dear Saleem Jawed

If you validate your standard from the API manufacturer against the primary reference standard then this is acceptable.

Regards

Maria

Maria Barrett
Senior Pharmacopoeial Scientist
British Pharmacopoeia Secretariat
MHRA
Buckingham Palace Road, London, SW1W 9SZ, UK
Telephone: 020 3080 6555
Email: maria.barrett@mhra.gsi.gov.uk
Stay connected: mhra.gov.uk/stayconnected
MHRA is a centre of the Medicines and Healthcare Products Regulatory Agency

________________________________________
From: Saleem Jawed- Manager QC  
Sent: 02 September 2013 09:51
To: Barrett, Maria
Cc: Holland, Dr Patience
Subject: RE: Enquiry from the BP Website
Dear Maria Barret,

Thanks for your prompt reply.

I've already read the below mentioned query on the site.

Presently the practice is we are qualifying working standards/ secondary reference standards using a primary reference standard (BPCRS, EPCRS or USPRS).

My question is can we replace the primary reference standard to API manufacturer supplied reference standard having complete characterization and if we can replace what are necessary supporting data we require for the same.

 

Warm Regards,

Saleem Jawed

From: Barrett, Maria [mailto:Maria.Barrett@mhra.gsi.gov.uk]
Sent: Monday, September 02, 2013 1:49 PM
To: saleem.jawed@optimusgenerics.com
Cc: Holland, Dr Patience
Subject: FW: Enquiry from the BP Website

Dear Saleem Jawed

In answer to your questions I have copied the information that is available on the questions and answers section on reference materials on the BP website.
Q. If we are testing to a BP monograph for a pharmaceutical dosage form,
can we use a different reference standard and treat as equivalent to the BPCRS?
A. To evaluate any product against a BP monograph, the reference standard specified in the monograph should be used. If the monograph specifies BPCRS,
the BPCRS should be used. If the monograph specifies EPCRS, the EPCRS should be used.
It is only acceptable to use a different reference material from the one specified in the monograph if the alternative has been validated against
the prescribed standard. Substituting without supporting data is not acceptable.
I hope that this helps.

Kind regards
Maria Barrett
Senior Pharmacopoeial Scientist
British Pharmacopoeia Secretariat
MHRA
Buckingham Palace Road, London, SW1W 9SZ, UK
Telephone: 020 3080 6555
Email: maria.barrett@mhra.gsi.gov.uk
Stay connected: mhra.gov.uk/stayconnected
MHRA is a centre of the Medicines and Healthcare Products Regulatory Agency

 

________________________________________
From: Saleem Jawed- Manager QC
Sent: 31 August 2013 12:06
To: BPCOM
Subject: Enquiry from the BP Website
Dear Sir / Madam,

I want to ask a query regarding the reference standard used in pharmaceutical testing.

• Is it mandatory to use the reference standard of pharmacopeial standard like supplied by BPCRS, EPCRS & USPRS only for qualification of working standard to be used in routine analysis?

• Can we use a primary standard(A standard having the complete characterization like assay, related substance, mass spectroscopy, NMR) supplied by the API manufacturers for preparation of working standard to be used in routine analysis?

Kindly revert for the same.

 

Edited Fri, Sep 13, 2013 10:21 AM

Can anyone guide me regarding any guideline present on qualification of working standards.

secondly, is it mandatory to do the related substance test for qualifying working standards.

We are performing description, identification water/LOD and assay.

 

Regards

 

Saleem Jawed

Hi Saleem,

First Your working or reference standard must pass the all test parameters against your specification.

Your procedure can be used If you are recertifying the working standard and justify it.

 

Regards

Hi Satya,

Yes we are using pre approved API for preparing working standards. For API to be qualified as working standard we are reanalyzing for description, identification water/LOD and assay.

Now additional related substance is required to be performed or not.

 

Regards

It is mandatory use for reference standard which evaluation of API working standard and structual elucidation is also required (NMR,IR,Mass,XRD,DSC etc.,)

 

We can assign the re-test period for 2 years from the date of evaluation and Assay by HPLC and RS/HPLC tests to be evaluate after one year and comparision data shall be made with previous results.

If the results well within the specified limits you can use another 1 year. If not new working standard shall be made.

 

 

 

 

 

 

Post Reply

You must be logged in and a member of this Groupsite in order to post a reply to this topic.
To post a reply, contact your group manager(s) Join this Groupsite