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jag009 ★★★ NJ, 2022-01-24 08:48 (960 d 00:33 ago) Posting: # 22747 Views: 3,496 |
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Hi folks, A weird question about an immediate release product. If I have 1) A BE study showing BE between a test and a reference at lower strength 2) A higher strength test product that is formulation proportional to the lower strength test product but the strengths are not interchangeable (meaning for example the lower strength product is 160 mg and the higher strength product is 500 mg). 3) Dissolution test lower vs higher strengths f2> 50. 4) I have efficacy and safety data for a reference product. Same molecule, immediate release and same strength as the highest strength test product. Based on the above, can I file a biowaiver for the higher strength test product so I don't have to run a PK BE study? This is an NDA. Thanks John |
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dshah ★★ India, 2022-01-24 12:01 (959 d 21:20 ago) @ jag009 Posting: # 22750 Views: 3,010 |
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Hi John! Interesting question but when we revisit guidelines, the biowaiver recommendation is mostly for lower strength formulation only. I believe that the criteria of not using higher strength due to safety/AE if justifiable, then may be used to support waiver using lower strength. Regards, Dshah |
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jag009 ★★★ NJ, 2022-01-24 16:09 (959 d 17:12 ago) @ dshah Posting: # 22753 Views: 2,998 |
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HI Dshah, ❝ Interesting question but when we revisit guidelines, the biowaiver recommendation is mostly for lower strength formulation only. I believe that the criteria of not using higher strength due to safety/AE if justifiable, then may be used to support waiver using lower strength. According to the guidance it seems possible. "For an NDA, biowaivers of a higher strength will be determined to be appropriate based on (1) clinical safety and/or efficacy studies including data on the dose and the desirability of the higher strength, (2) linear elimination kinetics over the therapeutic dose range, (3) the higher strength being proportionally similar to the lower strength, and (4) the same dissolution procedures being used for both strengths and similar dissolution results obtained. A dissolution profile should be generated for all strengths." thx John |
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dshah ★★ India, 2022-01-24 21:18 (959 d 12:03 ago) @ jag009 Posting: # 22755 Views: 2,960 |
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Thank you John! So what was the rational for conducting BE on lower strength rather than higher strength? Regards, Dshah |
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dshah ★★ India, 2022-02-03 20:07 (949 d 13:15 ago) @ jag009 Posting: # 22771 Views: 2,753 |
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Hi John! From the guideline- "The higher strengths of the test and reference products are proportionally similar to their corresponding lower strength" could be important as if the lower strength 160 mg and higher strength 500 mg are not interchangeable. Regards, Dshah |
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Ohlbe ★★★ France, 2022-01-24 13:16 (959 d 20:06 ago) @ jag009 Posting: # 22751 Views: 2,988 |
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Hi John, Does your drug show linear PK ? If not: does it show more-than-proportional increase (then the highest strength would be more sensitive to show differences in BA) or less-than-proportional increase (lowest strength would be more sensitive, giving you good arguments) ? — Regards Ohlbe |
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jag009 ★★★ NJ, 2022-01-24 16:06 (959 d 17:15 ago) @ Ohlbe Posting: # 22752 Views: 2,994 |
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Hi Ohlbe, ❝ Does your drug show linear PK ? If not: does it show more-than-proportional increase (then the highest strength would be more sensitive to show differences in BA) or less-than-proportional increase (lowest strength would be more sensitive, giving you good arguments) ? Yes its linear PK. I read the FDA guidance about Guidance, for NDA it seeems "possible" as long as one can provide safety and efficacy data. John |
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wienui ★ Germany/Oman, 2022-02-01 10:12 (951 d 23:09 ago) (edited by wienui on 2022-02-01 15:29) @ jag009 Posting: # 22768 Views: 2,866 |
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Hi John, ❝ Based on the above, can I file a biowaiver for the higher strength test product so I don't have to run a PK BE study? Are both strengths (low & high) follow the following EMA 5% & exceients rule? EMA : Amount of API must be < 5% of tablet core weight, and Amounts of excipients are same per strength, or Only the amount of a filler is changed to account for changes in API weight. — Cheers, Osama |
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