Chromatography Forum

Hi,

I have a deficiency letter from one authority that wants us ''Signal to noise ratio has been compliant (> 10) for both impurity A and impurity D at a concentration of 0.0003 mg/ml each. The corresponding LODs and LOQs for impurity A and impurity D should be indicated in terms of relative concentration in the finished product.''

Our results is below. We didn't perform LOD parameter in the validation because it is not necessary according to ICH.

Signal-to-Noise (S / N)
Compound Concentration (mg / mL) Acceptance Criteria Average Result
Impurity A 0.0003 not less than 10 19
Impurity D 0.0003 not less than 10 19

What is means ''relative concentration''?

Thank you

Is your product a liquid, and when you say 0.0003 mg/mL, do you mean that is the maximum possible impurity of an intended 100% liquid product? I.e. you're telling me that I can buy 1 mL of oily liquid from you, and your current assay will detect the impurities if at least 0.0003mg is present in my mL? If so, I don't think the deficiency letter is fair, because you're already giving a relative concentration.

If, however, your assay can detect anything in excess of 0.0003 mg/mL in a prepared solution of the intended product, then what they probably mean is they'd rather you express your LOD as a minimum percentage purity that you could detect. Their question is "is your assay guaranteed to detect any impurity present at > 0.1% of the intended product?". Their concern is that if your answer is "we can detect 0.0003 mg/mL of impurity" they need to ask "... but how concentrated was the intended product, because if you had only 0.003 mg/mL of intended product in your assay, you're telling us you could only detect a 10% impurity!"

Hi,

Our product is lyophilized powder.
The Test Solution Cons.(Sample) = 1.0 mg/mL
The LOQ solution Cons. = 0.0003 mg/mL

So, we can detected % 0.03 impurity level.
I didn't understand relative concentration. I have never calculated it, I don't know how can I calculate.

I think you've just done it. They wanted 0.03%, not 0.0003 mg/mL. I hope that's all it is, anyway! Good luck!

Hi,

Our product is lyophilized powder.
The Test Solution Cons.(Sample) = 1.0 mg/mL
The LOQ solution Cons. = 0.0003 mg/mL

So, we can detected % 0.03 impurity level.
I didn't understand relative concentration. I have never calculated it, I don't know how can I calculate.

... they just being very very formal , you were ok since the beginning