nobody nothing 2015-05-12 12:01 (3263 d 22:18 ago) Posting: # 14788 Views: 4,499 |
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Hi! Is this new? http://www.fdanews.com/ext/resources/files/05-15/05-05-15-BEstudiesguidance.pdf?1430840199 ...class III biowaivers for FDA--- — Kindest regards, nobody |
Helmut ★★★ Vienna, Austria, 2015-05-12 14:27 (3263 d 19:52 ago) @ nobody Posting: # 14791 Views: 3,842 |
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Hi nobody, ❝ Is this new? Yep. Samaya notified us last week. The FDA proudly announced the revision at the “Global Bioequivalence Harmonisation Initiative” (March 2015, Amsterdam). Harmonized with their own product-specific recommendations and to a good part with EMA’s. Doubtful whether Japan will ever board the ship. ❝ ...class III biowaivers for FDA---
— 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 |
nobody nothing 2015-05-12 15:14 (3263 d 19:05 ago) @ Helmut Posting: # 14792 Views: 4,022 |
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❝ ❝ Is this new? ❝ ❝ Yep. ... Or better, Nope? Sorry for the double posting (little busy lately, not following all threads), maybe we can merge the threads or somefink like that? The 2000 guideline I have here, on papyrus, as we had it in ancient times Edit: Moving/merging of threads/posts is not implemented in the current version of the Forum’s scripts (on the to-do-list for ages). Too lazy to fiddle around in the MySQL-DB. [Helmut] — Kindest regards, nobody |
jag009 ★★★ NJ, 2015-05-14 18:31 (3261 d 15:48 ago) @ Helmut Posting: # 14820 Views: 3,712 |
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❝ Yep. Samaya notified us last week. And the Test and Ref need to be super fast in dissolution time. 15 mins... for Class 3 For Class 1 they only ask for within 30mins... John |
Helmut ★★★ Vienna, Austria, 2015-05-14 20:51 (3261 d 13:28 ago) @ jag009 Posting: # 14822 Views: 3,672 |
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Hi John, ❝ And the Test and Ref need to be super fast in dissolution time. 15 mins... for Class 3 ❝ For Class 1 they only ask for within 30mins... Harmonized with EMA’s requirements in the BE-GL, Appendix III, Section II. — 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 |
luvblooms ★★ India, 2015-05-15 09:31 (3261 d 00:48 ago) @ nobody Posting: # 14823 Views: 3,727 |
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Hi John and HS What baffles me the most is a) There is no clarity on the triplicate Solubility data generation whether it need to be generated on one lot of API or on data of different/all the lots of API used in different batches of formulation (This is one of the most frequently asked Question on all the products which are filled through bio waiver approach and I will surely generate all the data in advance to keep them handy in case of a query) b) Highest strength or highest dose??? Between line 135-139 guidance says that “ A drug substance should be classified as highly soluble 135 when the highest strength is soluble in < 250 mL of aqueous media over the pH range of 1-6.8. In other words, the maximum dose divided by 250 should be greater than or equal to the lowest solubility observed over the entire pH range of 1-6.8 of 1-6.8.” There could be a difference in highest strength and highest dose; example Capecitabine. Highest strength is 500 mg but highest dose is much higher at 1250 mg/m² orally twice daily. So in such conditions what to be used? c) In case one have to take the body surface area for highest dose calculation for Cancer medicines or medicines which are dosed as per the body surface, what should be the standard body surface area to be taken to show the solubility? BSA details as per Wikipedia Child of 2 years--> 0.5 m² 9 years--> 1.07 m² 10 years--> 1.14 m² 12–13 years--> 1.33 m² Women--> 1.6 m² Men--> 1.9 m² There was an average BSA of 1.73 m2 for 3,000 cancer patients from 1990 to 1998 in a European Organisation for Research and Treatment of Cancer (EORTC) database. During 2005 there was an average BSA of 1.79 m2 for 3,613 adult cancer patients in the UK. Among them the average BSA for men was 1.91 m2 and for women was 1.71 m2. As per the label of Xeloda dose should be SURFACE AREA (M²)->TOTAL DAILY DOSE* (MG) ≤ 1.25------> 3000 1.26-1.37------> 3300 1.38-1.51------> 3600 1.52-1.65------> 4000 1.66-1.77------> 4300 1.78-1.91------> 4600 1.92-2.05------> 5000 2.06-2.17------> 5300 ≥ 2.18------> 5600 Now what should be the dose used for Solubility study? a) 2800 mg (derived from BSA of 2.18? b) 2300 mg (based on normal published BSA of cancer patients? There are many more crude thoughts on the guidance but it will take some time to formulate them in questions. — ~A happy Soul~ |
nobody nothing 2015-05-15 12:34 (3260 d 21:45 ago) @ luvblooms Posting: # 14824 Views: 3,633 |
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❝ What baffles me the most is ❝ ❝ a) ...of different/all the lots of API used in different batches of formulation... Use common sense: All relevant batches should be studied, IMHO ❝ b) Highest strength or highest dose??? ... Again: Common sense, only the WORST CASE, i.e. absolute highest therapeutic dose thinkable makes sense. If there is a "switch" from high to low solubility within the therapeutic dose range, might be interesting to the authority... ❝ c) In case one have to take the body surface area for highest dose calculation ... See b) — Kindest regards, nobody |
luvblooms ★★ India, 2015-05-15 14:09 (3260 d 20:10 ago) @ nobody Posting: # 14826 Views: 3,589 |
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Hi Nobody ❝ Use common sense: All relevant batches should be studied, IMHO Using coomen sense I mentioned that but I have a bit different run in with FDA on couple of products a) in one of our filing they didn't ask for data of any other lot of API b) In recent submission they asked for all the data ❝ ❝ b) Highest strength or highest dose??? ... ❝ ❝ Again: Common sense, only the WORST CASE, i.e. absolute highest therapeutic dose thinkable makes sense. If there is a "switch" from high to low solubility within the therapeutic dose range, might be interesting to the authority... Totally agreed to your point. But common sense also tells me that may be BSA of 2.18 will not be the right BSA for cancer patient. So does using the "absolute highest therapeutic dose thinkable" really make sense? If so why to cut it off at 5600 mg? Why not even higher? ❝ ❝ c) In case one have to take the body surface area for highest dose calculation ... Again the same augument! A recent study showed that in a total of 3613 patients receiving chemotherapy for head and neck, ovarian, lung, upper GI/pancreas, breast or colorectal cancers were included, The overall mean BSA was 1.79 m2 (95% CI 1.78–1.80) with a mean BSA for men of 1.91 m2 (1.90–1.92) and 1.71 m2 (1.70–1.72) for women. So why to use BSA of 2.18? In past we had the some arguments with FDA on the dose calculation using BSA and after long discussion FDA finally agreed on calculations based on BSA of 1.78-1.91 m2. So better to get clarity on the stupid questions that one have — ~A happy Soul~ |
nobody nothing 2015-05-15 18:40 (3260 d 15:39 ago) @ luvblooms Posting: # 14835 Views: 3,575 |
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Hi Luvbloom ❝ Using coomen sense I mentioned that but I have a bit different run in with FDA on couple of products ❝ a) in one of our filing they didn't ask for data of any other lot of API ❝ b) In recent submission they asked for all the data Learning curve ❝ ❝ ❝ b) Highest strength or highest dose??? ... ❝ Totally agreed to your point. But common sense also tells me that may be BSA of 2.18 will not be the right BSA for cancer patient. So does using the "absolute highest therapeutic dose thinkable" really make sense? ❝ If so why to cut it off at 5600 mg? Why not even higher? I don't get the the point here, sorry For a biowaiver the absolute highest dose makes sense to me. Only if you can show that e.g. 99% of patients receive "highly soluble" doses and only 1% is on "low solubility" dose in practice this would matter. IMHO ❝ ❝ ❝ c) In case one have to take the body surface area for highest dose calculation ... ❝ ❝ Again the same augument! So why to use BSA of 2.18? I never mentioned that figure ❝ In past we had the some arguments with FDA on the dose calculation using BSA and after long discussion FDA finally agreed on calculations based on BSA of 1.78-1.91 m2. Sounds good! Go ahead! If you want clarity write some comment to include the "dosing based on bodyweight" thing into the guidance with some sound suggestions (based on clinical practice) and see what happenz. You will never know before you start... Happy weekend! — Kindest regards, nobody |