Log in
Register|
Dr_Dan ★★ Germany, 2013-09-27 14:35 (4304 d 00:38 ago) Posting: # 11569 Views: 6,657 |
|
|
Dear all In general a generic product is a copy of the originator product. However, the quantitative composition of excipients is not known and sometimes the qualitative composition can not be copied due to patent issues. Applying for a BCS class biowaiver how can I demonstrate that the difference in quantitive and/or qualitative composition of my test product with regards to the the reference product does not: modulate/alter permeability of the drug influence intestinal residence time alter GI motility and permeability alter PK absorption profile without performing respective in vivo or in vitro tests? I am not talking about exotic exipients just the usual well established ones (Lactose, Microcrystalline Cellulose, Magnesium Stearate, Croscarmellose Sodium, Colloidal Silicon Dioxide, Hydroxypropyl Cellulose Starch, Sodium Starch etc.). I am looking forward to your reply. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
|
jag009 ★★★ NJ, 2013-09-27 23:44 (4303 d 15:29 ago) @ Dr_Dan Posting: # 11572 Views: 5,836 |
|
|
Hi, ❝ without performing respective in vivo or in vitro tests? Without in-vitro release testing? If you don't do this then what supportive data do you have? John |
|
luvblooms ★★ India, 2013-09-30 08:29 (4301 d 06:44 ago) @ Dr_Dan Posting: # 11575 Views: 5,579 |
|
|
Dear Dr. Dan ❝ Applying for a BCS class biowaiver how can I demonstrate that the difference in quantitive and/or qualitative composition of my test product with regards to the the reference product does not: ❝ modulate/alter permeability of the drug ❝ influence intestinal residence time ❝ alter GI motility and permeability ❝ alter PK absorption profile ❝ without performing respective in vivo or in vitro tests? How about doing a quick literature search? There are many published literature available about impact of excipient on bioavailability (see this), permeability, GIT residence time and so on. The examples what I mentioned was just to give you an idea, you can look for impact of specific ingredient/excipient in a similar way. Hope this will help. — ~A happy Soul~ |
|
Dr_Dan ★★ Germany, 2013-10-02 12:12 (4299 d 03:01 ago) @ luvblooms Posting: # 11587 Views: 5,498 |
|
|
Dear Luv ❝ There are many published literature available about impact of excipient on bioavailability (see this), permeability, GIT residence time and so on. This is my problem. 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 quantitative (and 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. Otherwise you could nearly kill every biowaiver approach, because you do not know the exact quantitative composition of the reference and how to decide which difference would become significant and relevant? Kind regards Dan — Kind regards and have a nice day Dr_Dan |
|
luvblooms ★★ India, 2013-10-03 07:53 (4298 d 07:20 ago) @ Dr_Dan Posting: # 11592 Views: 5,423 |
|
|
Dear Dan Agree to your point that there are ❝ an endless number of papers describing an impact of an excipient on a special drug substance. And yes they cause confusion too. Now coming to your point ❝ you do not know the exact quantitative composition of the reference and how to decide which difference would become significant and relevant? How about doing reverse engineering? Try using NIR or some other method (some time chemical methods works too) to estimate the excipient quantitatively. We have done it for one of the BCS class I drug for US and EU submission and did not faced much problem. (In that condition reference was having poloxamer and different amounts for US and EU, quantitative estimations helped) — ~A happy Soul~ |
Ing. Helmut Schütz