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srinivasuk ☆ India, 2014-11-30 09:53 (3794 d 00:08 ago) Posting: # 13956 Views: 8,028 |
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Dear all, We have the formulation of solid dosage form, API is BCS-Class-II and registered formulation. During processing of the the product we had some physical properties problem, to resolve many experiments carried out by using same excipients which are present in the registered formulation but not resolved. Finally we resolved by adding additional excipeint (1%) which was not present in the formulation. Same excipient was used by many other marketed leaders (formulation) of same molecule. Hence there is no incompatibility issue. To address this with regulatory authorities (TGA) how we can proceed (with scientific justification). Justification require: There will not be any impact on Bioavailability/Bioequivalence with addition of the additional excipient which is not present in the registered formulation. We have done the comparative dissolution studies in release media and compared with previously manufactured batch dissolution data, data is complying there is no difference. Hope some body can guide in this regard. Thanks in advance Rgds, Srini Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2014-11-30 15:24 (3793 d 18:37 ago) @ srinivasuk Posting: # 13957 Views: 6,635 |
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Hi Srini, ❝ Justification require: There will not be any impact on Bioavailability/Bioequivalence with addition of the additional excipient which is not present in the registered formulation. Since the drug is BCS Class II and you have an additional excipient nobody will be able to give you such a “justification”. TGA’s BE-GL covers biowaivers for BCS Class I and – under certain conditions – Class III. Perform a biostudy. — 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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nobody nothing 2014-11-30 21:44 (3793 d 12:17 ago) @ srinivasuk Posting: # 13958 Views: 6,745 |
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afaik only WHO considers (some limited) class II APIs egligilbe for biowaivers. Look up literature for ibuprofen to have details on limitations for this approach, has been discussed here in the past iirc... Regards nobody — Kindest regards, nobody |
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Dr_Dan ★★ Germany, 2014-12-02 10:34 (3791 d 23:27 ago) @ nobody Posting: # 13964 Views: 6,587 |
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Dear all Some time ago I started a discussion about excipients (see this link) which faded out without result. So I thought this might be a good opportunity to restart. I would like to know if there is a chance to justify a different qualitative composition for a biowaiver if well established excipients are used (Lactose, Microcrystalline Cellulose, Magnesium Stearate, Croscarmellose Sodium, Colloidal Silicon Dioxide, Hydroxypropyl Cellulose Starch, Sodium Starch etc.). My Problem is that you will find an endless number of papers describing an impact of an excipient on a special drug substance. What I need is a rationale that at least for drugs considered for a biowaiver the difference in qualitative composition would not affect the in-vivo performance as long as in vitro dissolution tests show similarity between the test product and the reference. Do you have an idea? I am looking Forward to your reply. Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
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nobody nothing 2014-12-02 11:38 (3791 d 22:23 ago) @ Dr_Dan Posting: # 13966 Views: 6,427 |
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I don't think there is kind of "generic" justification, I would go for a specific API, specific excipient and regulator... In depth analysis from known and unknown unknows from the literature. Piece of work but cheaper and faster than biostudy. In case of no success (during Sci Adv) go ahead with BE studie, or?  — Kindest regards, nobody |
Ing. Helmut Schütz