2018-02-25 09:49

Posting: # 18460
Views: 2,540

 biowaiver-acceptable dissolution&proportional similarity [Dissolution / BCS / IVIVC]

Hello everyone, how to understand the two prerequisites for a biowaiver of additional strengths? :confused: can you present detailed cases? thanks.

Edit: Category changed; see also this post #1. [Helmut]
Vienna, Austria,
2018-02-25 13:20

@ powell
Posting: # 18461
Views: 2,163

 Strength biowaiver

Hi powell,

I suggest:
  1. Cardot J-M, García-Arieta A, Paixão P, Taševská I, Davit B. Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches. AAPS J. 2016;18(4):1039–46. doi:10.1208/s12248-016-9915-0.
  2. Cardot J-M, García-Arieta A, Paixão P, Taševská I, Davit B. Implementing the additional strength bio­waiver for generics: EMA recommended approaches and challenges for a US-FDA submission. Eur J Pharm Sci. 2018;111:399–408. doi:10.1016/j.ejps.2017.10.013.
Both papers contain case studies.

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. ☼
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giang nidqc

2018-08-22 13:01
(edited by giang nidqc on 2018-08-23 03:40)

@ Helmut
Posting: # 19196
Views: 1,308

 Strength biowaiver

Dear Helmut, I've read the two articles above and have a question.
FDA stated: "Active and inactive ingredients are not in exactly the same proportion between different strengths as stated above, but the ratios of inactive ingredients to total weight of the dosage form are within the limits defined by the SUPAC-IR and SUPAC-MR guidances (up to Level II)."
I'm confusing by the words. Could the proportion of the active ingredient change?
For example: Drug Y is formulated as a IR tablets of 4 and 16 mg strengths with total mass of 204 and 101 mg, respectively. The same inactive ingredients are used for both strength with same propotions out of the total weight, except for filler ingredient (to account for the change of the active subtance).
Could biowaiver be applied for 4-mg strength in this case? The articles above don't have example like this.
I'm a newbie in this field, so please excuse for my little knowledge. And my English is not so good too. Thanks!

Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5[Helmut]

2018-08-24 19:44

@ giang nidqc
Posting: # 19198
Views: 1,239

 Strength biowaiver


Up to my know how proportional similarity could be define in one of two ways for FDA:

(1)all active and inactive ingredients are in exactly the same proportion (percentage) between different strengths: in all strength the percentage of API and inactive ingredients are similar (mass are different between strength but percentage remains identical): for example if a single bulk of granulate is existing the mass is increased proportionally to the strength for each strength;
(2)for high-potency drug substances (where the amount of active drug substance in the dosage form is relatively low) an additional option is existing, the total weight of the dosage form should remain nearly the same for all strengths (for example for FDA within ± 10 % of the total weight of the biostudy strength), the same inactive ingredients should be used for all strengths, and the change in any strength is obtained by altering the amount of the active ingredients and possibly one or more of the inactive ingredients. For example mass of formulation is similar between all strengths (for example when API is decrease lactose is increased to keep mass identical).

for FDA specifically, for Abbreviated New Drug Applications (ANDAs) for generic drug products if active and inactive ingredients are not compositionally proportional between different strengths, the strengths can be considered proportionally similar with adequate justification (such as in vivo dosage form proportionality studies that demonstrate equivalent BA).

Rules for Europe are close except for(2) where mass must be identical or only decrease by the amount of API and only one filler could be used to compensate it and API limit is fixed at 5% for all strengths.

Hope that could help you

best regards,

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