(153 d 11:11 ago)
Posting: # 23641
I am posting these questions for getting clarification, to know the industry practice and the regulatory acceptance in the following two different cases.
For FDC formulations like Memantine & Donepezil, metronidazole and Tetracycline, Amlodipine & celecoxib, etc with simultaneous analysis in bioanalytical. Already we have proved selectivity, P&A, and all matrix stabilities in validation.
whether a specificity experiment has to be performed in validation? i.e., spiking the ULOQ concentration or anticipated cmax concentration in LLOQ and blank. or other approaches.
In a study design like Fluphenazine hydrochloride (To prevent severe dystonia, consider administering benztropine tablets before and during the study duration) concomitant medication is administered, in such cases of studies during validation whether specificity i.e., spiking the ULOQ concentration or cmax concentration in LLOQ and blank proving is sufficient or all matrix stabilities in presence of the concomitant drug is required.
During subject sample analysis whether QCs should have both analytes of interest and the concomitant drug Cmax spiked.
Kindly share your practice and inputs.
Edit: Please don’t post twice. I deleted the other post. [Helmut]
(147 d 10:24 ago)
Posting: # 23659
My opinion is that your validation should mimic the actual study condition. In BE studies of FDC, plasma samples contains all the analytes of interest and hence CC/QC during validation should contain the other analyte at ULOQ concentration or cmax concentration.
What is opinion of other (bioanalytical) experts?
(144 d 09:48 ago)
Posting: # 23667
According to the ICH M10 guideline, section 3.2.8:
For fixed dose combination products and specifically labelled drug regimens, the freeze-thaw, bench-top and long-term stability tests of an analyte in matrix should be conducted with the matrix spiked with all of the dosed compounds.
I would consider that both cases you describe fall under this category. Meaning that even if you already have stability data for each analyte separately, you would still need to repeat the stability evaluation with the combined products.
I would also consider that in both cases described, you should perform a specificity experiment, considering the provisions of section 3.2.2.
In your case 2: if you are not measuring the concomitant medication, I would not consider it necessary for the QC samples to contain that analyte, if specificity and stability have been demonstrated as above.