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Regaffairs ● 2006-10-06 12:38 (6791 d 11:55 ago) Posting: # 284 Views: 9,078 |
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Hi, Solicit your opinion / guidance on the below. We had submitted generic version of X product without BE. The Waiver for the same based on the BCS classification. Off late the review of the dossier has raised question on the BE with notification to submit the data by conducting the same. To update, the registration samples were submitted from the commercial lot and assigned 24 months shelf life. Now the proposed shelf life of 24 months is complete for the product and QC analysis of the last due point indicate the samples to be well confined to the shelf life specification. Hence could you confirm that the samples manufactured 24 months back will still be a good candidate for BE as Test product versus the fresh lot of the innovator ? Is there any time regulatory time frame where in the time lag between the formulation manufactured and the BE conducted is freezed / discussed ? If not, how could I support the BE using the old samples to the regulatory body ? If not I may have to take fresh commercial lot and do the same. Thanks |
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H_Rotter ★ Germany, 2006-10-06 15:21 (6791 d 09:11 ago) @ Regaffairs Posting: # 285 Views: 7,442 |
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Hi Regaffairs! I'm a little bit confused, and I think we need some clarification...  ❝ We had submitted generic version of X product without BE. The Waiver for the same based on the BCS classification. Off late the review of the dossier has raised question on the BE with notification to submit the data by conducting the same. You only may get a waiver for an in vivo BE study, if all of the conditions stated in the respective guideline (slightly different from country to country) are fulfilled, i.e., submitting dissolution similarity by an f2 >50. Do you mean, you haven't submitted any in vitro data, and are now asked to show them, or your application for a biowaiver was rejected and the regulator now wants to see a biostudy? Whitout this clarification, it will be difficult to answer your questions.  regards, Hermann |
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Regaffairs ● 2006-10-06 16:24 (6791 d 08:08 ago) @ H_Rotter Posting: # 287 Views: 7,553 |
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Dear Mr.Rotter, Further to your quoted reply please find a suitable response ❝ You only may get a waiver for an in vivo BE study, if all of the conditions stated in the respective guideline (slightly different from country to country) are fulfilled, i.e., submitting dissolution similarity by an f2 >50. ❝ Do you mean, you haven't submitted any in vitro data, and are now asked to show them, or your application for a biowaiver was rejected and the regulator now wants to see a biostudy? We have claimed BCS waiver based on the applicable guideline and also have submitted the invitro dissolution data performed in the required regulatory media. The disso profile met the applicable requirement with more than 85% release in desired 30 minutes and F2 values > 50. The application was reversed citing information on biostudy. Thanks -- Edit: Original quotes restored. [Helmut] |
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H_Rotter ★ Germany, 2006-10-06 17:07 (6791 d 07:26 ago) @ Regaffairs Posting: # 289 Views: 7,501 |
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Hi Regaffairs, now I - hopefully - got your point  ❝ We have claimed BCS waiver based on the applicable guideline and also have submitted the invitro dissolution data performed in the required regulatory media. The disso profile met the applicable requirement with more than 85% release in desired 30 minutes and F2 values > 50. ❝ ❝ The application was reversed citing information on biostudy. Remember that guidelines are guidelines, not laws... You may apply for a biowaiver, but there is no guarantee that it will be granted. Did the regulator give any explanations for the rejection? If you decide to go for a biostudy, I would suggest do perform it with new batches of both test and reference, because: ❝ Is there any time regulatory time frame where in the time lag between the formulation manufactured and the BE conducted is freezed / discussed ? IMHO no, but... ❝ If not, how could I support the BE using the old samples to the regulatory body ? You mentioned in your original post, that after 24 months your product is still within the shelf life specifications (95% or 90% or ...?). Assuming that you don't have enough samples of the reference product you used in the in vitro study left to perform a biostudy, you will have to use a new batch of the reference anyhow. By this you will have to increase your sample size, since you should expect a lower point estimate in the comparison Testold vs. Refnew. I am not sure, whether the regulator will accept this study - even if you are not discouraged from such a case in a guideline... Regards, Hermann |
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Ahmed meeran ● 2006-10-10 15:49 (6787 d 08:44 ago) @ Regaffairs Posting: # 299 Views: 7,512 |
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Dear Reg affairs, Kindly clarify the following point w. r. to biowaiver.
With regards, D.Ahmed Meeran |
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H_Rotter ★ Germany, 2006-10-10 16:19 (6787 d 08:14 ago) @ Ahmed meeran Posting: # 301 Views: 7,524 |
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Hi Ahmed, you summarized the important points, but since (as Regaiffairs has already stated in his/her previous post: ❝ We have claimed BCS waiver based on the applicable guideline [...] BTW, which country's MOH (Ministry of Health?) are you talking about - guidelines differ... Regards, Hermann |
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Ahmed meeran ● 2006-10-10 16:41 (6787 d 07:51 ago) @ H_Rotter Posting: # 302 Views: 7,596 |
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Dear Hermann, Yes MOH = Ministry of Health. The guidlines which I have referred is from MCC South Africa Dec 2003 version. Of course the guidline on Biowaivers can slightly vary on limits but in my opinion over all the summarised points are important to consider when any BW is sought. regaffairs though quoted ..but did not spell out on which point exactly the MOH rejected the BW application.. hence I have asked whether the points quoted are taken care enough ... Of course the final decision to grant BW or not is with the MOH. But if the BW is rejected due any other reason other than I have summarized, if regaffairs can uncover the details so that our group members can be benefited. With regards, Ahmed |
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H_Rotter ★ Germany, 2006-10-10 17:02 (6787 d 07:30 ago) @ Ahmed meeran Posting: # 303 Views: 7,471 |
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Hi Ahmed! ❝ Yes MOH = Ministry of Health. The guidlines which I have referred is from MCC South Africa Dec 2003 version. OK, maybe you are interested in the new draft (as far as I can see, no major changes). ❝ Of course the guidline on Biowaivers can slightly vary on limits but in my opinion over all the summarised points are important to consider when any BW is sought. Full ACK ❝ regaffairs though quoted ..but did not spell out on which point exactly the MOH rejected the BW application.. hence I have asked whether the points quoted are taken care enough ... Of course the final decision to grant BW or not is with the MOH. ❝ ❝ But if the BW is rejected due any other reason other than I have summarized, if regaffairs can uncover the details so that our group members can be benefited. Yes, this would be a very valuable input - we learn more from failures than from successes... Regards, Hermann |
Ing. Helmut Schütz