MR generic application [Regulatives / Guidelines]

posted by vixen – Czechia, 2020-03-27 21:20  – Posting: # 21304
Views: 427

Hello Mikkabel,

I'd say no chance for that. The guideline is pretty clear about it - you have to test at least two strengths in fasting conditions (no "bracketing" possible without testing two extremes). I guess you will be lucky if you are able to bracket one of the three strengths anyway (what if the extremes selected according to the different factors are not always the same two strengths?).

Of note, the waiver for lower strength is possible in case of multiple unit formulations. Should you wonder why the requirements differ for single vs multiple unit formulations, the following article may offer some insights:

"Except for the multiple-unit dosage forms where various strengths differ only in the number of units, a lower strength of an ER drug product made either by making proportional change in composition or by only matching in vitro drug release may or may not be bioequivalent to the higher strength. Hence, allowing biowaiver for lower strengths of ER products based on in vitro drug release in the absence of an IVIVC or IVIVR (...) can result in compromised product performance and increased risks to the patients. (...)
For a monolithic dosage form, smaller dosage unit size of the proportionally similar lower strength generally results in a shorter diffusional pathlength and/or time for complete hydration in a matrix system, thinner coating film in the membrane-controlled reservoir, or semipermeable membrane in the osmotic devices because higher S/V provides larger normalized surface. As a result, drug release is usually faster than that of the higher strength counterpart."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779102/

Best regards,
vixen

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