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Darborn ☆ Taiwan, 2024-09-30 03:14 (221 d 16:24 ago) Posting: # 24206 Views: 1,920 |
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Hi Everyone, In the section "2.1.6 Dose or Strength to be Studied" of ICH M13A, it's said: In cases of documented less than proportional increases in AUC and/or Cmax with increasing dose over the range of strengths proposed, BE should be established with the lowest strength if this is due to saturation of absorption. If the less than proportional increase in AUC and/or Cmax with increasing dose is due to limited drug solubility, BE studies should be conducted with both the lowest and highest strengths. If the reason for less than dose proportionality is unknown, BE studies should be conducted with both the lowest and highest strengths. If the drug product is highrisk (see Section 2.1.5), in general, a fasting and fed BE study at the highest strength and a fasting BE study at the lowest strength are needed. I'm wondering the sentences in red. Does it mean ALL drug product that is highrisk should conduct a fasting and fed BE study at the highest strength PLUS a fasting BE study at the lowest strength? OR this is only applied to highrisk drug products with less than proportional increase in AUC and/or Cmax with increasing dose.  Thanks for any thought on this |
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BEQool ★ 2024-10-07 12:33 (214 d 07:05 ago) @ Darborn Posting: # 24221 Views: 1,524 |
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Hello, I was wondering the exact same thing but I think that this red text applies just to high-risk products with less than proportional increases in AUC and/or Cmax with increasing dose over the range of strengths proposed (the latter explanation of yours). Otherwise this would have been written at least in a seperate paragraph as this whole paragraph is talking about less than proportional increases in AUC and/or Cmax with increasing dose. Regards BEQool |
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Darborn ☆ Taiwan, 2024-10-08 02:58 (213 d 16:40 ago) @ BEQool Posting: # 24223 Views: 1,486 |
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Thanks BEQool for the reply, I totally agree with your point that a separate paragraph will be needed if it truly means that all high-risk products should be conducting those studies. However, this still needs to be clarified by the authorities.  Best regard |
Ing. Helmut Schütz