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zuzanna ☆ Poland, 2024-07-31 09:54 (50 d 01:57 ago) Posting: # 24108 Views: 1,661 |
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Dear Forum members, Please share your thoughts regarding the timing of meal in the situation below: SmPC of Reference: administer the drug at the beginning of meal EMA guideline: In case the study is to be performed during fed conditions, the timing of administration of the drug product in relation to food intake is recommended to be according to the SmPC of the originator product. ICH M13A draft guideline: For a fed BE study, it is recommended that subjects start the meal 30 minutes before administration of the drug product and consume the meal within 30 minutes (and no reference to the label/SmPC) First sampling point: 20 min (sic!), then 40 min etc… What would you do in this situation: 1) start the meal within 5 min following drug administration (and keep or move the first sampling point?) or 2) start the meal 30 min before drug administration (let’s say “standard fed conditions” but not fully in line with SmPC)? I’m confusing, grateful for all suggestions! |
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Helmut ★★★   Vienna, Austria, 2024-07-31 11:14 (50 d 00:37 ago) @ zuzanna Posting: # 24109 Views: 1,493 |
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Hi Zuzanna, the ICH M13A was already adopted on 23 July 2024 (step 4). Let’s see when it will appear on the ICH’s website and which changes to the draft have been made. Interesting that the Q&A document is already available. See for example the EMA’s Bioanalytical Method Validation Guideline of 2011 stating that it was superseded by ICH M10 of 2022. As long as this does not happen for the BE guideline as well (ICH M13A in step 5 = implemented), it is still applicable. — 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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zuzanna ☆ Poland, 2024-07-31 12:32 (49 d 23:20 ago) @ Helmut Posting: # 24110 Views: 1,433 |
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Thanks Helmut, but based on your experience/gut feeling, what option would you choose in this case? meal before or after the drug admonistration? |
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Helmut ★★★ Vienna, Austria, 2024-07-31 14:21 (49 d 21:30 ago) @ zuzanna Posting: # 24111 Views: 1,435 |
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Hi Zuzanna, ❝ but based on your experience/gut feeling, what option would you choose in this case? meal before or after the drug admonistration? So far I followed the EMA’s GL (i.e., administration according to the SmPC of the originator). Furthermore: I try not to think with my gut. In the meantime M13A was published. No changes in this respect (page 10): For a BE study conducted under fed conditions, it is recommended that subjects start the meal 30 minutes before administration of the drug product and completely consume the meal within 30 minutes. Contrary to us mere mortals who have to maintain a version control of documents, agencies (and the ICH!) don’t care. Although the draft is still on the ICH’s server, it’s no more linked on the website. — 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 |
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zuzanna ☆ Poland, 2024-07-31 15:47 (49 d 20:05 ago) @ Helmut Posting: # 24113 Views: 1,416 |
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Wow, this is called "timing", did we pressure ICH to make the guidelines published, wiretapping? spying? 😉 Luckily I saved a draft version on the server, checkmate 😉 Still a hard nut to crack 😉 But I'm a little afraid that the EMA guidelines will be replaced unexpectedly quickly. Thanks for all the suggestions and: It is through science that we prove, but through intuition that we discover Henri Poincare |
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ElMaestro ★★★ Denmark, 2024-07-31 16:14 (49 d 19:37 ago) @ zuzanna Posting: # 24114 Views: 1,419 |
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Hi Zuzana, the ICH document was written in a generic fashion, it does not take into consideration specific cases like yours. This fully justifies a deviation from the guidance. It is for that reason that I think EU regulators would suggest to dose as per SmPC and not as per ICH guidance if you ask for scientific advice. So that is what I would lean towards. Gut feeling only. — Pass or fail! ElMaestro |
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zuzanna ☆ Poland, 2024-08-01 14:49 (48 d 21:02 ago) @ ElMaestro Posting: # 24121 Views: 1,345 |
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Hi ElMaestro, Thanks for sharing your thoughts, it sounds really reasonable. There is one more problem - in this case, the first sampling point was scheduled for 20 minutes. The subjects should eat their meal within 30 minutes and I am afraid that moving this point to 40 minutes may be associated with the risk of a high "Cmax at first sampling point" number  |
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qualityassurance ★ 2024-08-02 07:09 (48 d 04:42 ago) @ zuzanna Posting: # 24124 Views: 1,303 |
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Hello Zuzana, ❝ There is one more problem - in this case, the first sampling point was scheduled for 20 minutes.❝ You can withdraw blood while subject is having their meal. Do you see any challenge here? Regards, QA |
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ElMaestro ★★★ Denmark, 2024-08-02 17:14 (47 d 18:37 ago) @ qualityassurance Posting: # 24126 Views: 1,275 |
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Hello again, ❝ You can withdraw blood while subject is having their meal. Do you see any challenge here? That is one thing. Another aspect is of course that in these special cases there is good reason to take a scientific advice. Also, from the regulators perspective there will often be some thinking along the lines of picking the conditions that maximise the chances of detecting a difference, if a difference exists. If you can argue that "meal 30 minutes before dosing" is more sensitive to detect a difference than "dosing at the start of the meal" then there's your answer. In practice, this often strands on a lack of evidence, though. I do not know of any generic company much interested in studying the phenomenon to get an answer to it. But where did the t=20 minute first sample enter the story? Is there a product-specific guideline? — Pass or fail! ElMaestro |
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zuzanna ☆ Poland, 2024-08-03 23:16 (46 d 12:35 ago) @ qualityassurance Posting: # 24127 Views: 1,199 |
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Hi QA, ❝ You can withdraw blood while subject is having their meal. Do you see any challenge here? Yes, the challenge is indeed there. The median Tmax is expected to be 1.5h, and the range may start at 40 min or even earlier. I'm afraid to have DLs about the unreliable PK profile with some Tmax at the first sampling points. Hi ElMaestro, Yes, the SA will be the best option here, but, unfortunately, we need to start the study ASAP  I have found one info from Q&A EMA BE guideline that for MR products meal 30min before drug administration is considered "the worse case scenario" compared to SmPC timing. But first, this is for MR products, and second, it was in 2010 
Edit: Standard quotes restored; see also this post #8. Please don’t use small fonts for long text. [Helmut] |
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qualityassurance ★ 2024-08-05 14:45 (44 d 21:07 ago) @ zuzanna Posting: # 24130 Views: 1,072 |
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Hello Zuzana, ❝ Yes, the challenge is indeed there. The median Tmax is expected to be 1.5h, and the range may start at 40 min or even earlier. I'm afraid to have DLs about the unreliable PK profile with some Tmax at the first sampling points.❝ If you anticipate Tmax at 20 minutes, add other blood collection at 10 minutes. You can collect blood while subjects are having their meal. You can specify this also in protocol. In this way I do not anticipate any DLs. Regards, QA |
Ing. Helmut Schütz