Log in
Register|
jag009 ★★★ NJ, 2022-09-02 00:16 (769 d 22:06 ago) Posting: # 23258 Views: 4,731 |
|
|
Hi all, A question, has anyone ever filed an ANDA with great BE study results (90% Cmax and AUC ~ 98-100%, adequate sample size, ISCV~25%) but with f2 << 50 (F2=30 due to differences in very early timepts) in the comparative dissolution study based on method recommended in the BE guidance for IR product? 1) F2 is not really applicable for IR, correct? The sampling timepts were 5, 10 ,20, 30, 45mins. I know that f2 is not really relevant if % dissolve > 85% in 15 mins, but my product is >85% after 20 mins.. 2) is f2 based on guidance recommendation even relevant if the BE results are so good? Thx john |
|
wienui ★ Germany/Oman, 2022-09-02 01:22 (769 d 21:01 ago) @ jag009 Posting: # 23259 Views: 4,110 |
|
|
Hi John & all, ❝ A question, has anyone ever filed an ANDA with great BE study results (90% Cmax and AUC ~ 98-100%, adequate sample size, ISCV~25%) but with f2 << 50 (F2=30 due to differences in very early timepts) in the comparative dissolution study based on method recommended in the BE guidance for IR product? normally, In vivo study overrules in vitro dissolution study i.e, even if f2 doesn't show the similarity between the test & reference formulations, the two formulations are considered as therapeutic equivalence. ❝ 1) F2 is not really applicable for IR, correct? The sampling timepts were 5, 10 ,20, 30, 45mins. I know that f2 is not really relevant if % dissolve > 85% in 15 mins, but my product is >85% after 20 mins.. What about if you start with sampling time points @ 10 min ( EMA) and not @ 5min ( FDA)? have you tried with bootstrapping to overcome the high variability in the early sampling time points? ❝ 2) is f2 based on guidance recommendation even relevant if the BE results are so good? f2 is a supportive in vitro method to the in Vivo crucial BE study to prove the therapeutic equivalence. — Cheers, Osama |
|
jag009 ★★★ NJ, 2022-09-02 02:29 (769 d 19:54 ago) @ wienui Posting: # 23260 Views: 4,062 |
|
|
Thanks Osama. That's my thinking as well since the BE studies were ~ 100% in ratios and reasonably sized. But explaining to those non-pk/bioparm management f**ls who keep asking for risk assessment BS is a challenge. ❝ What about if you start with sampling time points @ 10 min ( EMA) and not @ 5min ( FDA)? ❝ have you tried with bootstrapping to overcome the high variability in the early sampling time points? Unfortunately the guidance asked for 5 and 10 mins and on... evaluating the data now to see if there is need to evaluate.. john |
|
dshah ★★ India, 2022-09-02 13:37 (769 d 08:46 ago) @ jag009 Posting: # 23261 Views: 4,150 |
|
|
Hi John! I think the talk is about BE strength only, but what about other strength waiver? Regards, Divyen Shah |
|
jag009 ★★★ NJ, 2022-09-05 01:13 (766 d 21:10 ago) @ dshah Posting: # 23267 Views: 4,064 |
|
|
HI Divyen, ❝ I think the talk is about BE strength only, but what about other strength waiver? John |
|
dshah ★★ India, 2022-09-05 13:16 (766 d 09:07 ago) @ jag009 Posting: # 23269 Views: 3,998 |
|
|
Hi John! You guess it right John. Kindly refer below PSG for example. ![[image]](img/uploaded/image10.jpg) So, if only BE strength is in the focus, there is no need to worry. Regards, Divyen |
|
wienui ★ Germany/Oman, 2022-09-06 01:29 (765 d 20:54 ago) @ dshah Posting: # 23270 Views: 3,946 |
|
|
Hi Divyen, ❝ You guess it right John. ❝ Kindly refer below PSG for example. ❝ I think you have asked this question several times and we have discussed it before, for example here: https://forum.bebac.at/mix_entry.php?id=21680#p21742 and here https://forum.bebac.at/mix_entry.php?id=22747#p22768 By the way, I will hold a presentation at The 4th MENA Regulatory Conference on Bioequivalence, Biowaivers, Bioanalysis, and Dissolution about this topic on September 19th, 2022, in Amman, Jordan. "Additional strength Biowaiver: Practical Regulatory Similarities & Differences Approaches" http://rbbbd.com/IPRC_Program.aspx — Cheers, Osama |
|
dshah ★★ India, 2022-09-06 02:49 (765 d 19:34 ago) @ wienui Posting: # 23272 Views: 3,933 |
|
|
Dear Osama! I was not asking the question but suggesting to focus on other strength waiver as well. Regards, Divyen |
|
jag009 ★★★ NJ, 2022-09-08 21:32 (763 d 00:51 ago) @ dshah Posting: # 23280 Views: 3,848 |
|
|
Hi, ❝ You guess it right John. If you fail f2 comparison between highest and lowest (or other) strengths then they wont grant you the waiver unless you run bio, even if you claim formulations are proportional. John |
|
dshah ★★ India, 2022-09-09 19:56 (762 d 02:27 ago) @ jag009 Posting: # 23290 Views: 3,869 |
|
|
Hi John! ❝ If you fail f2 comparison between highest and lowest (or other) strengths then they wont grant you the waiver unless you run bio, even if you claim formulations are proportional. You can try multi tablet for dissolution, or perform bootstrap for f2, try model dependent and independent approaches to prove similarity in dissolution. Regards, Divyen |
|
dshah ★★ India, 2022-09-15 13:09 (756 d 09:14 ago) @ jag009 Posting: # 23296 Views: 3,645 |
|
|
Hi John! Below decision tree might help you. ![[image]](img/uploaded/image841.png) Regards, Divyen |
|
Rayhope ☆ India, 2022-09-15 17:13 (756 d 05:10 ago) @ dshah Posting: # 23298 Views: 3,611 |
|
|
❝ Below decision tree might help you. ❝ HI Divyen , Please let me know from where u got this flow chart. Please name the guidance will be helpfull. |
|
dshah ★★ India, 2022-09-20 18:02 (751 d 04:20 ago) @ Rayhope Posting: # 23309 Views: 3,506 |
|
|
Dear Rayhope: The decision tree is from article: In Vitro Dissolution Profiles Similarity Assessment in Support of Drug Product Quality: What, How, When—Workshop Summary Report. Regards, Divyen |
Ing. Helmut Schütz