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Helmut ★★★   Vienna, Austria, 2014-12-31 14:40 (4193 d 08:02 ago) Posting: # 14206 Views: 5,340 |
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Dear all, and the methylphenidate-story continues. On Dec 18 the FDA published a new draft for MPH extended release suspension. In line with the ER tablet guidance, three partial AUCs instead of only two in the Sep 2012 draft (see also here about cut-points). But: 2×2 crossovers (no S × F interaction assessed in fully replicated studies). I don’t understand these guys. Submit your comments to regulations.gov until Feb 23, 2015. — 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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AngusMcLean ★★ USA, 2015-01-01 22:25 (4192 d 00:17 ago) @ Helmut Posting: # 14208 Views: 4,378 |
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Helmut: Thank you for this reference. It seems that this new Guidance focuses on an MR suspension type formulation akin to a Quillivant type product available here in the US. In the Guidance it mentions in the beginning that Design: Single-dose, two-way crossover in vivo This appears to be a regular BE study. It then goes on to say The fasting BE study may be conducted in a single dose, two-treatment, two-sequence, four-period, replicated design. Now this contrasts with the previous methylphendidate Concerta guidance, which states up front Design: Single-dose, two-treatment, four-period, two-sequence, fully replicated crossover in vivo Therefore my interpretation of what they are saying for the suspension is that, although the study design is firstly envisaged as Single-dose two-way crossover in vivo, the sponsor is given the option of running Single-dose, two-treatment, four-period, two-sequence, fully replicated crossover study in vivo. |
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Helmut ★★★ Vienna, Austria, 2015-01-02 00:07 (4191 d 22:34 ago) @ AngusMcLean Posting: # 14209 Views: 4,307 |
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Hi Angus, ❝ […] the sponsor is given the option of running Single-dose, two-treatment, four-period, two-sequence, fully replicated crossover study in vivo. Correct. But that’s a trivial statement, right? According to FDA’s practice (for years!) one can always perform a replicate study instead of simple cross-over. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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AngusMcLean ★★ USA, 2015-01-02 01:22 (4191 d 21:20 ago) @ Helmut Posting: # 14210 Views: 4,369 |
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Helmut: I am not sure whether that general statement can be made. Have you seen any FDA documents stating their policy in such terms? I know that if an innovator has set precedent with a BE study design for an MR formulation during their development program then a generic company will tend to do the same study. For example if the innovator has performed BE studies with a non-highly variable drug (non replicate) and determined BE then I do not know if a generic company during their program would be allowed {if they wish} to use a replicate design BE for their formulation. Or would the FDA direct then to use a non-replicate design. My background is not in generics; it is in 505 b(2). Angus |
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Helmut ★★★ Vienna, Austria, 2015-01-02 02:11 (4191 d 20:30 ago) @ AngusMcLean Posting: # 14211 Views: 4,346 |
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Hi Angus, ❝ Helmut: I am not sure whether that general statement can be made. Have you seen any FDA documents stating their policy in such terms? I don’t need a policy. That’s basic statistics. From any replicate design you can infer average BE. ❝ I know that if an innovator has set precedent with a BE study design for an MR formulation during their development program then a generic company will tend to do the same study. That’s stupid unjustified copy-and-paste. ❝ For example if the innovator has performed BE studies with a non-highly variable drug (non replicate) and determined BE then I do not know if a generic company during their program would be allowed {if they wish} to use a replicate design BE for their formulation. Or would the FDA direct then to use a non-replicate design. Doesn’t make sense. The applicability of replicate designs is not limited to RSABE (upscaling for HVDs, downscaling for NTIDS) or estimating S×F for ER MPH. I agree with one European regulator who once said “From a scientific perspective I would like to see all BE studies in a fully replicated design”. OK, if you want a quote: On David Bourne’s PKPD-list this question popped up and on 30 Jun 2002 FDA’s Mei-Ling Chen replied: No restrictions are imposed to anyone wishing to conduct a replicate design bioequivalence study. In fact, replicate designs are encouraged from a scientific point of view. (my emphasis)— Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Ing. Helmut Schütz