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olacy ☆ Hungary, 2007-06-06 18:15 (6937 d 11:34 ago) Posting: # 782 Views: 7,202 |
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Dear All, I could not find in the guidelines that what should be done regarding the following issue. You had made a given formulation and it passed the biostudy. No problem till this point. :) However, the API supplier has changed and the new API is quite different from the previous one (impurity profile, residual solvents, etc.). The new API is also acceptable but DIFFERENT. Can I use the results of the biostudy conducted with the preceding API? Do I have to prove that the differences between the API would not alter significantly the bioavailability (and the safety) of the API? If so, how? If a slight difference is acceptable, what is the extent? Thanks in advance! Best regards, Laszlo |
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Helmut ★★★   Vienna, Austria, 2007-06-06 18:38 (6937 d 11:11 ago) @ olacy Posting: # 783 Views: 6,439 |
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Dear Lázló! ❝ You had made a given formulation and it passed the biostudy. No problem till this point. :) ❝ However, the API supplier has changed and the new API is quite different from the previous one (impurity profile, residual solvents, etc.). ❝ The new API is also acceptable but DIFFERENT. ❝ Can I use the results of the biostudy conducted with the preceding API? As an entry point I would suggest FDA's 'Scale-Up and Post-Approval Changes' (SUPAC) Guideline. IMHO you are subject to a change in 'Manufacturing, Level 3' (section VI, page 21pp). ❝ Can I use the results of the biostudy conducted with the preceding API? No. ❝ Do I have to prove that the differences between the API would not alter significantly the bioavailability (and the safety) of the API? Such a change would call for a biostudy (the classical example of phenytoin fatalities in the late 70ies was a change in the manufacturing process of a supplier, which was not communicated to the company). ❝ If so, how? If you are successful with an IVIVC, you may apply for a biowaiver… — 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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olacy ☆ Hungary, 2007-06-07 16:08 (6936 d 13:41 ago) @ Helmut Posting: # 786 Views: 6,010 |
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Dear Helmut! Thanks for the answers. I saw earlier the guideline mentioned. I read it through quickly but I have not found what should be done in case of API changes. It refers to the changes of excipients the site of manufacture and the technological process. This problem is not too rare, it is quite frequent that an API supplier changes the manufacturing method and it finally leads to a different API. Not to mention changing the API supplier, which could result an absolutely different API. I would not think that all changes in the API mean that the bioequivalence study should be repeated. But I could not find any references, guidelines which clearly declare what should be done in such cases. Thanks again! Best regards, Laszlo Edit: Full quote removed. Please see this post! [HS] |
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Helmut ★★★ Vienna, Austria, 2007-06-07 16:42 (6936 d 13:07 ago) @ olacy Posting: # 787 Views: 6,204 |
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Dear Lázló! ❝ I would not think that all changes in the API mean that the bioequivalence study should be repeated. But I could not find any references, guidelines which clearly declare what should be done in such cases. IMHO Level 1-2 changes do not call for a BE study.  — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Ing. Helmut Schütz