javier ☆ Spain, 2017-03-29 01:21 (2579 d 10:04 ago) Posting: # 17196 Views: 4,111 |
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Dear All First and foremost, I have been looking for a while in older post regarding this question, but although i have found some ideas, i dont have the main picture, so i kindly ask you to ilustrate all the beginners like me that we look here for enlightment Regarding Bioequivalence studies on drugs with long half life, for example monoclonal antibodies or filgastrim,etc.... guidelines EMA and FDA says "AUCt will be ok if it is at least 80% of AUC∞." the big question is how to calculate the amount of time to reach this conclussion about AUCt is at least 80% if you only have the information of the SmPC? (with so many important PK information omited ) on another way: how to forecast the number of days that you will need to takes blood samples to cover the magic number of 80%? in other post i have read that 2-4 times Tmax will be enought as a thumb rule, but if we are talking about intravenous infusion and long half life 's drugs i dont know if this rule will be applicable in this case or not Thanks in advance for your time and if you ask me for the existence of this forum. I think a bebac book with all the information contained in the forum would be top list in amazon for a while.. Best regards Javier |
javier ☆ Spain, 2017-03-30 15:36 (2577 d 19:49 ago) @ javier Posting: # 17212 Views: 3,459 |
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If anyone knows a guideline or PK book when this issue es explained it would be very helpful too thanks in advance |
ElMaestro ★★★ Denmark, 2017-03-30 15:54 (2577 d 19:31 ago) @ javier Posting: # 17213 Views: 3,563 |
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Hi javier, ❝ the big question is how to calculate the amount of time to reach this conclussion about AUCt is at least 80% if you only have the information of the SmPC? (with so many important PK information omited ) ❝ ❝ on another way: how to forecast the number of days that you will need to takes blood samples to cover the magic number of 80%? This is not what you want to do. This what your boss wants you to do. Biologics are much less defined that synthetic drugs, especially if they are produced by eukaryotic cells (S. cerevisiae etc). There are all sorts of little games going on with them which is not well understood and well controlled even in the most strictly regulated GMP facility. Check for example your batch release chromatograms (if you have them, if chromatolophystique is used where you work): You will see chromatograms that look like porcupines or someone having a really bad hair-day and where the individual spikes correspond to variants of post-translational modfication and where you don't really know -exactly which ones are active -their exact structure -how potent they are -and which ones aren't potent/active. All these species may have different properties in terms of ADME. You will likely see differences in apparent t½ for Test and Ref. I recommend that you do a pilot trial and forget all about the info on the SPC. You are facing a source of error that is potentially much much higher than what you are used to from synthetics. I think a pilot trial in a dedicated phase I facility is also the ethically correct thing to do. — Pass or fail! ElMaestro |
javier ☆ Spain, 2017-03-30 16:12 (2577 d 19:13 ago) @ ElMaestro Posting: # 17214 Views: 3,529 |
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Hi ElMaestro! ❝ This is not what you want to do. This what your boss wants you to do. I couldnt agree more with you ❝ I recommend that you do a pilot trial and forget all about the info on the SPC. You are facing a source of error that is potentially much much higher than what you are used to from synthetics. ❝ I think a pilot trial in a dedicated phase I facility is also the ethically correct thing to do. One more question,assuming that we will do the pilot trial, (in our case would be a healthy volunteer study because there is no safety concern about the drug)and the end of the day the question is the same right, How can we sure that que are taking enough sampling to cover the 80% of AUC-inf? Forgive me for insisting but at heart i want to know how to do it just only for improving my kownlegde in pharmacology Thanks in advance |
ElMaestro ★★★ Denmark, 2017-03-30 17:08 (2577 d 18:18 ago) (edited by ElMaestro on 2017-03-30 18:25) @ javier Posting: # 17215 Views: 3,533 |
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Hola javier, ❝ One more question,assuming that we will do the pilot trial, (in our case would be a healthy volunteer study because there is no safety concern about the drug)and the end of the day the question is the same right, How can we sure that que are taking enough sampling to cover the 80% of AUC-inf? The purpose of your pilot is dual: To get an idea of variability so that your can dimension your pivotal trial appropriately, and to establish the time by which AUCt>0.8*AUCinf in the majority of (expected future) trial patients/volunteers. — Pass or fail! ElMaestro |
javier ☆ Spain, 2017-03-31 00:44 (2577 d 10:42 ago) @ ElMaestro Posting: # 17216 Views: 3,459 |
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❝ The purpose of your pilot is dual: To get an idea of variability so that your can dimension your pivotal trial appropriately, and to establish the time by which AUCt>0.8*AUCinf in the majority of (expected future) trial patients/volunteers. Thanks again for the answer (y por el tiempo que me has dedicado en contestar a la pregunta, que no es poca cosa) Best regards Javier Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Helmut] |