Bioequivalence and Bioavailability Forum • Reference scaled BE

Reference scaled BE - EMA [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2010-04-28 16:46 (5480 d 02:02 ago) – Posting: # 5258
Views: 36,147

Dear Dave!

❝ In general, I would always take the guidance literally, instead of scientifically.

I never did that (and will not do so in the future).

❝ For instance, when the EMEA general BA/BE guidance said: "The interval must be prospectively defined e.g. 0.75-1.33" I never took the reciprocal of 0.75 to give 1.33 repeating, even though in theory that would make the most sense. This is for the sole reason that you never know when you are going to hit THAT regulator - the type A that doesn't care what makes scientific sense and takes every digit literally.

Well I always stated the limits based on the acceptable difference (∆). For the ‘old’ extended range it’s 25%. So in my protocols I gave L=1-∆ and U=1/L. Never got a deficiency letter.

❝ So when the new guidance says 0.760, even though you and I both know that it doesn't back-calculate to a perfect 30.0% CV, guess what I would recommend using?

The back-calculated CV was just an example. I would recommend to use the exact value.

❝ This problem pops up again and again. Look at the older Canadian

❝ guidelines for narrow therapeutics:

❝ http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/guide-ld/bio/critical_dose_critique-eng.pdf

❝ The requirements are 90.0-112.0%, not 90.0-111.11 repeating. They didn’t even round down, they rounded UP. So I became a to-the-letter kind of guy, despite my academic side crying “unfair! unfair!”. I learned to suppress those little hairs standing up at the back of my neck.

Right, it’s also in the recent draft. I asked Eric Ormsby about that at the last BioInternational Conference and he said they have suggested this value for simplicity. I guess Eric has a low opinion about the IQ of people in the pharmaceutical industry. :cool:

❝ […] There were 3 stop overs to that trip, and it took almost 12 hours to get there!!!!

Come on. Last week I stranded in Brussels (you know, the volcano-business) and it took me five hours queuing to get a train ticket and finally 21 hours (including change trains six times) to go back to Vienna. ;-)

—
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

Complete thread:

Reference scaled BE - FDA (and FARTSSIE update) ddubins 2010-04-26 20:28 [RSABE / ABEL]
- Reference scaled ABE - FDA d_labes 2010-04-27 08:58
  - Reference scaled ABE - FDA ElMaestro 2010-04-27 13:39
    - Factor 2 is unbiased d_labes 2010-04-27 14:30
    - Biased bonus from MoM d_labes 2010-05-04 12:10
      - Biased bonus from MoM ElMaestro 2010-05-04 12:54
        
        Mixed MoM d_labes 2010-05-04 14:40
        
        Mixed MoM ElMaestro 2010-05-04 15:08
        
        R and G, CSH and UN d_labes 2010-05-05 10:42
        
        A sailor gets confused ElMaestro 2010-05-05 11:49
        
        Confused V/Z matratzen and tips d_labes 2010-05-05 14:49
        
        superb post! ElMaestro 2010-05-05 21:32
        
        Gambling with UN d_labes 2010-05-06 11:00
        
        Mixed MoM yjlee168 2010-05-05 09:12
- Reference scaled BE - FDA (and FARTSSIE update) KR 2010-04-27 13:14
- Reference scaled BE - EMA Helmut 2010-04-27 14:58
  - Reference scaled BE - EMA ddubins 2010-04-27 17:52
    - Partial replicate design and FDA ABE code d_labes 2010-04-28 09:47
    - Reference scaled BE - EMAHelmut 2010-04-28 14:46
    - Switching - null sWR d_labes 2010-05-04 14:04
- The unknown x d_labes 2010-05-06 13:26
  - The unknown x jdetlor 2010-09-28 17:22
    - Unknown x corrected? d_labes 2010-10-01 12:14
      - Unknown x corrected? Qilex 2016-09-21 12:25
        
        Official unknown x d_labes 2016-09-21 13:22