Chromatography Forum

Can anybody tell me, what should be the limit of RSD for Method Precision study for an API. (the assay limit is NLT 98.0 % and NMT 101 %.

Mostly % RSD limit is NMT 2.0 % for 6 samples. Should this limit be made stringent to 1.0 %


Regards,

Hi Surbhi
As per which regulation your following for method validation. If it is as per ICH then for 6 injection it should be less than 1.0% but if it is as per FDA it should be less than 2.0%.

Hi Surbhi
As per which regulation your following for method validation. If it is as per ICH then for 6 injection it should be less than 1.0% but if it is as per FDA it should be less than 2.0%.

not that 2% is appropriate w/ a 3% acceptance window...

Thanks.

I have referred the ICH guidelines for AMV. Can you tell me where the limit of 1 % is mentioned.

As it is API, and the limit being 98-101 %, I will fix the acceptance criteria as 1 % only.

Regards,

Refer the guidline 2a and 2b of ICH. Visit www.ich.org in that one quality guidlines it is given

Refer the guidline 2a and 2b of ICH. Visit www.ich.org in that one quality guidlines it is given

2A and 2B are obsolete, and their replacement, Q2, is now in revision 1. From memory, no % limits for precision are provided in ICH Q2, as it covers method validation.

As DR notes above, precision should be suitable for the specification range.

Bruce Hamilton

As rightly said by Bruce, no limits are stated in ICH, Q2a and Q2b. I have referred it thoroughly.

Also as per DR, i agree that if the specification limit is 98.0 - 101.0 %, % RSD limit for the AMV studies should be made more stringent, ie. 1 %.

Still further input required from all who are on line

Regards,

Dear Surabhi:

In an analytical method validation, we normally set limits for precision as follows: RSD for Area <1.0% (n =10), and RSD for RT <0.5% (n=10).

Note: In normal runs, we set RSD<3% (n=6).

The basis for this is the document titled "Reviewer Guidance: Validation of
Chromatographic Methods". (Dated 1994). According to the guidance:

As part of methods validation, a minimum of 10 injections
with an RSD of 1% is recommended. With the methods
for release and stability studies, an RSD of 1% RSD for
precision of the system suitability tests for at least five
injections (n 5) for the active drug either in drug substance
or drug product is desirable. For low level impurities, higher
variations may be acceptable.

The link:
http://www.fda.gov/CDER/GUIDANCE/cmc3.pdf

ICH Q2A and Q2B have basically definitions.

Here is another page that I normally use to justify (read: defend) my validation criteria with our QA people (our QA people are not chemists):
http://www.labcompliance.com/methods/meth_val.htm
(My apology to labcompliance.com for the deep-linking!).

Hope that this helps

Alfred

Thanks a lot Alfred.

A very nice response received from your end.

Further inputs on AMV are appreciated.

Regards,