Log in
Register|
Helmut ★★★   Vienna, Austria, 2011-04-22 17:16 (5543 d 06:33 ago) Posting: # 6935 Views: 5,912 |
|
|
Dear all, found another goodie. Draft Guideline EMA/CHMP/600958/2010 (17 February 2011, published 14 March 2011) Appendix IV of the Guideline on the Investigation on Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1): Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1 Table 3.1 Pharmacokinetic data for <analyte> +-----------------+---------------------------+Wow - that's clever! Arithmetic means for AUC, Cmax (lognormal); tmax (discrete). End of consultation (deadline for comments): 31 May 2011. — 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 |
|
ElMaestro ★★★ Denmark, 2011-04-23 02:23 (5542 d 21:26 ago) @ Helmut Posting: # 6936 Views: 5,080 |
|
|
Great post HS. Page 8: Certain bioanalytical parameters are marked with a "1" for "Might not be applicable for the given analytical method". Autosampler isn't one of them. So, if you happen to do analysis w/o an autosampler then you're out? Or is this a candiate for an N/A somehow? Page 8: Linearity? ... I think they mean r2, or that's at least my hope. It is still very meaningful to use quadratic equations now and then. Page 8: Plasma only? Or did they mean biological matrix, whether it be plasma, serum, whole blood or urine? — Pass or fail! ElMaestro |
|
Helmut ★★★ Vienna, Austria, 2011-04-24 17:43 (5541 d 06:06 ago) @ ElMaestro Posting: # 6938 Views: 4,984 |
|
|
Hi ElMaestro! ❝ Page 8: Linearity? ... I think they mean r2, or that's at least my hope. It is still very meaningful to use quadratic equations now and then. Yes, that’s ridiculous. r or r2 is meaningless, without giving the calibration function, the number (and location[*]) of data points, and the weighting scheme. How can anybody come up with just one value? This section is about validation of the method, so values should be presented from all batches. BTW, not only quadratic (in MS/MS and fluorescence if a large concentration range is covered) are common, but what about 4- and 5-parameter logistic regression in ligand-bindig assays‽ Anybody is invited to tell me the purposefulness of r there. Linearity of a nonlinear-function? BTW, the anonymous authors should have read the draft bioanalytical GL. r is not mentioned there at all; the text talks only about calibration curves (sic!). ❝ Page 8: Plasma only? Or did they mean biological matrix, whether it be plasma, serum, whole blood or urine? Again, the draft GL: The main objective of method validation is to demonstrate the reliability of a particular method for the determination of an analyte concentration in a specific biological matrix, such as blood, plasma, urine, saliva or tissue. Moreover, validation should be performed using the same anticoagulant as for the study samples. Matrix. What else. BTW, the wonderful document doesn’t ask for the anticoagulant.  The worst I have seen was a method validated in EDTA-plasma, and study's samples were serum.[*] OK, OK, must report the concentration of the CC. — 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 |
|
Helmut ★★★ Vienna, Austria, 2011-11-21 19:12 (5330 d 03:37 ago) @ ElMaestro Posting: # 7690 Views: 4,579 |
|
|
Hi ElMaestro, the final version [Appendix IV of the Guideline on the Investigation on Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1): Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1] was published last Friday (see here, effective with 1 June 2012; comments). After a first look it seems to be OK now.  Some footnotes added on page 8: 4Arithmetic Means (±SD) tmax3 3 Median (Min, Max) 4 Arithmetic Means (±SD) may be substituted by Geometric Mean (±CV%) page 10: Added Biological matrix <e.g. Plasma, Whole Blood, Urine> Removed Linearity <r> More detailed information about Matrix Factor requested ‘Plasma’ replaced by ‘Biological matrix’ — 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 |
|
ElMaestro ★★★ Denmark, 2011-11-21 19:43 (5330 d 03:06 ago) @ Helmut Posting: # 7693 Views: 4,441 |
|
|
Hi HS, ❝ the final version [Appendix IV of the Guideline on the Investigation on Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1): Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1] was published last Friday (see here, effective with 1 June 2012; comments). After a first look it seems to be OK now. Thanks for this info. It looks to me like stakeholder #4 abstained from using terms such "ridiculous"... I guess stakeholder #4 remembered to take his medicine the day the comments were due?!? I like this one: "Anticoagulant is an important detail but no regulatory decision is based on that." Alright seeing it that way, the same goes for Geometric Mean (±CV%). So why do these hafta be reported then? Re. the Geometric Mean, I really need to make a rant about it one of the next days on this forum. A misnomer if there ever was one. Geometric Means are not always LSMeans, but the world seems to be oblivious to this fact. Best regards, EM. |
|
Helmut ★★★ Vienna, Austria, 2011-11-21 22:07 (5330 d 00:42 ago) @ ElMaestro Posting: # 7695 Views: 4,345 |
|
|
Dear ElMaestro! ❝ It looks to me like stakeholder #4 abstained from using terms such "ridiculous"... I guess stakeholder #4 remembered to take his medicine the day the comments were due?!? Oh yes, I've heard that stakeholder #4 is very earnest in such situations. On other days (I've heard) he runs around screaming and head-banging. ❝ Re. the Geometric Mean, I really need to make a rant about it one of the next days on this forum. A misnomer if there ever was one. Geometric Means are not always LSMeans, but the world seems to be oblivious to this fact. Stakeholder #4 commented on that as well. Wasn’t accepted. He failed with median (quartiles) for tmax also. What does the range tell us? — 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 |
|
Ohlbe ★★★ France, 2011-11-22 00:07 (5329 d 22:42 ago) @ ElMaestro Posting: # 7696 Views: 4,388 |
|
|
Dear ElMaestro, ❝ It looks to me like stakeholder #4 abstained from using terms such "ridiculous"... I guess stakeholder #4 remembered to take his medicine the day the comments were due?!? "Ridiculous" is when stakeholder #4 does take his medicine. In other circumstances I've heard him talk of "bullshit", while addressing the Chairman of the very group which just released this new document Regards Ohlbe — Regards Ohlbe |
|
ElMaestro ★★★ Denmark, 2011-11-22 11:11 (5329 d 11:38 ago) @ Ohlbe Posting: # 7698 Views: 4,358 |
|
|
Dear Ohlbe, ❝ "Ridiculous" is when stakeholder #4 does take his medicine. In other circumstances I've heard him talk of "bullshit", while addressing the Chairman of the very group which just released this new document Oh dear...  I think (imagine / am not certain) the chairman is just about the only person who is not at fault. Anyways, it is an interesting choice of language that surely will be perceived as a peaceful gesture. Do you think stakeholder #4 should double his dose or is he completely beyond pharmacological reach? Best regards, EM. |
Ing. Helmut Schütz