Bioequivalence and Bioavailability Forum • Applicability of reference-scaling

Applicability of reference-scaling [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2017-05-10 16:10 (2874 d 00:16 ago) – Posting: # 17343
Views: 23,411

Hi nobody,

❝ ❝ Nobody knows how to deal with this story. :-(

❝

❝ ... sorry, no.

Didn’t mean you. Nobody ≠ nobody (case sensitive). ;-)

❝ […] At least you need to write a new, Chapter 2.5-like overview on the pk, pharmacology, safety to make the assessor sleep well next night after reading your application for a generic. On the other hand, assessors for originator's MAs have a much, much better sleep (better sleeping pills?), in my experience...

Well, maybe assessors should take stimulants instead of sleeping pills. Les Benet’s claim “HVD(P)s are safe drugs” was based on two arguments:

If an HVD(P) does not have a flat dose-response curve, there would have been safety/efficacy issues in phase III and the originator’s product would not get approved.
- Correct, if the originator does not ‘forget’ to report serious AEs (remember Boehringer’s dabigatran…).
No safety/efficacy issues were found in clinical practice.
- OK, we all know that pharmacovigilance isn’t very sensitive and the system not well implemented in some countries. However, 32% of 222 novel therapeutics were affected by a postmarket safety event.*

Hence, I would rather say:

Reference-scaling for the innovator’s product

Should not be allowed when scaling up to the production batch size.
Should not be allowed for major formulation changes for a certain time after approval (e.g., five years).
If there were no relevant issues, it should be allowed.
Easy for the FDA because the product-specific guidance is issued fast and updated regularly.
Takes a while for the EMA, but some already exist (e.g., posaconazole).

Reference-scaling for a generic product

Should generally be allowed (#3 for the innovator is applicable).

Just my two ¢ worth.

Downing NS, Shah ND, Aminawung JA, Pease AM, Zeitoun J-D, Krumholz HM, Ross JS. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010. JAMA. 2017; 317(18): 1854–63. doi:10.1001/jama.2017.5150.

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Helmut Schütz

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Complete thread:

Highly Variable Drug BE Justification jag009 2017-03-20 04:42 [Regulatives / Guidelines]
- Highly Variable Drug BE Justification ElMaestro 2017-03-20 06:55
  - Study costs: Replicate vs. 2×2×2 Helmut 2017-03-20 13:12
    - Study costs: Replicate seems to be cheaper VStus 2017-03-21 12:49
      - Study costs: Replicate seems to be cheaper Dr_Dan 2017-03-21 13:06
        
        Study costs: Replicate seems to be cheaper Helmut 2017-03-21 14:50
        
        expected power d_labes 2017-03-21 15:16
        Doesn't hurt! VStus 2017-03-23 14:24
    - Study costs: Replicate vs. 2×2×2 mahmoud-teaima 2017-03-23 08:17
    - Study costs: Replicate vs. 2×2×2 M.tareq 2017-05-07 21:21
      - Replicate vs. 2×2×2 (ethics?) Helmut 2017-05-08 14:21
        
        Replicate vs. 2×2×2 (ethics?) nobody 2017-05-08 14:52
        
        Applicability of reference-scalingHelmut 2017-05-10 14:10
        
        Replicate vs. 2×2×2 M.tareq 2017-05-14 23:04
        
        Replicate vs. 2×2×2 Helmut 2017-05-15 19:07
        
        Replicate vs. 2×2×2 M.tareq 2017-05-15 21:02
        Regulators view of HVD drugs DavidManteigas 2017-05-16 12:41
        
        Regulators view of HVD drugs Helmut 2017-05-16 15:01
        What's the problem? ElMaestro 2017-05-17 03:30
        
        What's the problem? nobody 2017-05-17 07:48
        
        What's the problem? nobody 2017-05-17 09:31
        
        What's the problem? DavidManteigas 2017-05-17 11:25
        
        What's the problem? ElMaestro 2017-05-17 12:07
        
        What's the problem? kumarnaidu 2017-07-11 14:43
        
        What's the problem? ElMaestro 2017-07-11 14:56