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jag009 ★★★ NJ, 2012-03-14 17:57 (5219 d 07:46 ago) Posting: # 8275 Views: 5,735 |
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Gentleman, Could you please provide guidance on ANDA criteria for a prodrug on the following scenario? For prodrugs, BE assessment will be made based on the active metabolite because the levels of the prodrug is too low, yes? What if for a drug product both a fasting and a fed study is needed and the prodrug levels in the fed study is measurable. Thanks |
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drgunasakaran1 ★★  2012-03-16 07:24 (5217 d 18:19 ago) @ jag009 Posting: # 8282 Views: 5,091 |
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Dear Mr.Jag, As per Canadian BE guidance “Conduct and Analysis of Comparative Bioavailability studies”, a pro-drug is to be treated as a 'parent drug'. That is, if the substance released from the dosage form is absorbed intact and is reliably measurable in the systemic circulation, it should be used in the assessment of Bioequivalence. Fasting state: Bioequivalence estimation of the active metabolite of the prodrug is allowed if
If the prodrug levels are measurable in the fed state, you need to analyse Prodrug for bioequivalence estimation. However, quantification of its metabolite levels may sometimes be helpful, e.g., to explain extreme values caused by metabolic changes within a subject. In the above case, bioequivalence estimation will be based both on the Pro-drug and its metabolite. — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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Helmut ★★★   Vienna, Austria, 2012-03-16 13:27 (5217 d 12:15 ago) @ drgunasakaran1 Posting: # 8283 Views: 5,387 |
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Dear Gunasakaran & John! ❝ As per Canadian BE guidance […] Since John mentioned the term “ANDA” in his/her post I guess we should refer to FDA’s practice – which is inconsistent. The prodrug should be targeted whenever possible. If we have a look at product-specific guidances, we find different cases, e.g.,
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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jag009 ★★★ NJ, 2012-03-16 21:05 (5217 d 04:38 ago) @ Helmut Posting: # 8288 Views: 5,060 |
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Thanks Gunasakaran & Helmut, Here is the issue, The immediate release innovator I am looking at is to be given with meal (as per product monograph) due to it's higher bioavailability. FDA does not have a guidance on whether both fast and fed studies are needed (none on their website). The parent compound is a prodrug with little or no detectable concentrations under fasting (because it's rapidly converted into the active metabolite form); The active metabolite has high concentrations. When given under fed conditions, both compounds increase in concentrations and are detectable. Do I need to do both fasting and fed studies for an ANDA? If so, does that mean for the fasting ANDA study I need to demonstrate equivalence based on the active metabolite since parent prodrug is mostly BLQ? And for the fed study then I will need to demonstrate equivalence based on the parent drug (prodrug) since it's measurable? Thank you. Jag |
Ing. Helmut Schütz