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jag009 ★★★ NJ, 2014-07-23 17:17 (3558 d 12:23 ago) Posting: # 13300 Views: 5,678 |
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Hi all, Can someone give me some hints on running a BE study involving injectable device? i.e., design, sources of variability etc? Thanks John |
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Dr_Dan ★★ Germany, 2014-07-25 14:18 (3556 d 15:22 ago) @ jag009 Posting: # 13312 Views: 4,923 |
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Dear John In order to understand your question could you please provide some more information? Are you talking about some kind of intramuscular/subcutaneous depot formulation? Is the device biodegradable or must it be removed by surgery? In general such devices act over a long period of time and therefore you will end up with a parallel group design. Variability strongly depends on the solubility of the drug, the release mechanism and the metabolism of the study participants. To my experience the variability will be comparably high. Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
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jag009 ★★★ NJ, 2014-08-05 21:30 (3545 d 08:09 ago) @ Dr_Dan Posting: # 13336 Views: 4,723 |
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Thanks Dr. Dan, It involves an intramuscular auto-injector. The subject basically push the needle into their thigh and the drug is delivered automatically. Subject then removes the device themselves. My concern is that some folks here suggested the subjects will do their own drug administration --> This can introduce a lot of errors when compared to having a drug administration person doing it. John |
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Dr_Dan ★★ Germany, 2014-08-06 09:45 (3544 d 19:55 ago) @ jag009 Posting: # 13341 Views: 4,696 |
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Dear John I agree with ElMaestro, the better option is to have only one person to perform the administration. A BE study is an in-vivo quality test and you do not have to reflect the clinical situation. Your aim must be to keep the variability low and one way would be to have only one person to perform the administration. As I assume for testing an intramuscular auto-injector a standard 2x2x2 design should be possible and therefore you should avoid the parallel design in order to remove the intersubject variability. I hope this helps Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
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jag009 ★★★ NJ, 2014-08-08 18:53 (3542 d 10:47 ago) @ Dr_Dan Posting: # 13355 Views: 4,668 |
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Hi Dr. Dan, I fully agree but then we heard from our RA group that some company ran something similar for a different drug(allowing the clinic staff to do the drug administration) but FDA came back and said they wanted to see subjects do their own drug administration... John |
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Dr_Dan ★★ Germany, 2014-08-11 01:48 (3540 d 03:52 ago) @ jag009 Posting: # 13358 Views: 4,673 |
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Dear John As always one assessor's opinion does not necessarily reflect the opinion of the FDA. The aim of a BE study is to show differences in formulations. As long as there is no difference in the way of administration or in technical performance I do not see the necessity of having the subjects doing selfadministration. Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
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Ohlbe ★★★ France, 2014-08-25 01:40 (3526 d 04:00 ago) @ Dr_Dan Posting: # 13424 Views: 4,512 |
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Dear Dan and John, ❝ The aim of a BE study is to show differences in formulations. As long as there is no difference in the way of administration or in technical performance. True. But if the administration device differs between the two products and there is a technical difficulty in administering one of them, this may result in a different bioavailability if patients don't do the administration properly. In this regard I think it makes sense to ask the subjects to self-administer the products. — Regards Ohlbe |
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ElMaestro ★★★ Denmark, 2014-08-06 01:39 (3545 d 04:00 ago) @ jag009 Posting: # 13339 Views: 4,797 |
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Hi John, ❝ Can someone give me some hints on running a BE study involving injectable device? i.e., design, sources of variability etc? This is a situation very similar to what you encounter when you develop generic inhalers: Train volunteers very well to do the self-administration, or, sometimes a better and approvable option, let the staff do the administration. At any rate, the clinical staff has to be trained very well too. If using the self option: Staff may be able to literally make an "x" on musculus vastus lateralis or whereever with a marker and the task for the volunteer is to hit the "x". Note that a lot of healthy volunteers cannot in practice self-inject even after signing icf and will chicken out. If the product is an epi-pen generic then originator training devices are available. Your own formulation should be accompanied by training dummies too. Device training takes quite a bit of resources but isn't per se difficult - it just need to be done thoroughly. Training should be done before each dosing and individually for each subject. A relevant goal is to make the volunteer show the staff three to five consecutive successful administrations just prior to time zero. If the staff are to administer the drug the staff can demonstrate the same to your own clinical trial manager/staff/someone in the presence of monitor. Relying on simple pre-trial training e.g. the evening before first period will likely give you results that are all over the place. The chicken factor can be very pronounced (can be your biggest source of variation) and even if this is a drug that has few side-effects volunteers might opt out after period 1 in case of crossovers. If a parallel trial is an option then that might be better in practice. Thus my initial proposal is a parallel group design with training the evening prior to dosing and with individual training before drug administration in the morning. — Pass or fail! ElMaestro |
Ing. Helmut Schütz