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Helmut
Hero
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Vienna, Austria,
2018-05-10 13:55

Posting: # 18760
Views: 943
 

 Necessity of MD study based on expected accumulation [Regulatives / Guidelines]

Dear all,

the EMA requires multiple dose studies of prolonged release products if the mean AUCτ–∞ of both products after a single dose is >10% of AUC0–∞,1,2 whereas Health Canada was less restrictive (>20%).2,3 However, according to the current guidance of HC steady-state studies are not generally required.4

Discovered this goody about BE of extended release veterinary products:5,6,7
  • For extended release formulations intended for repeated dosing, demonstration of BE should be based on multiple dose studies if there is accumulation between doses (i.e., if there will be at least a 2-fold increase in drug concentrations at steady state as compared to that observed after a single dose). […] If there is no or negligible accumulation, single dose BE data could also be sufficient for extended release formulations intended for repeated dosing.


[image]

Kudos. Accumulation <2 (AUCτ–∞ <50% of AUC0–∞) is considered negligible. :thumb up:


  1. European Medicines Agency, Committee for Medicinal Products for Human Use. Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms. 20 November 2014. EMA/CPMP/EWP/280/96 Corr1.
  2. Scheerans C, Heinig R, Mueck W. Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms. Biopharm Drug Dis. 2015;36:93–103. doi:10.1002/bdd.1923. Open access.
  3. Health Canada, Health Products and Food Branch. Guidance for Industry. Conduct and Analysis of Bioavailability and Bioequivalence Studies – Part B: Oral Modified Release Formulations. 1996.
  4. Health Canada, Health Products and Food Branch. Guidance Document. Comparative Bioavailability Standards: Formulations Used for Systemic Effects. 22 May 2012. Online.
  5. International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products. Bioequivalence: Blood Level Bioequivalence Study. August 2015. VICH GL52.
  6. European Medicines Agency, Committee for Medicinal Products for Veterinary Use. VICH GL52. Bioequivalence: blood level bioequivalence study. 10 September 2015. EMA/CVMP/VICH/751935/2013 – Corr.1.
  7. Food and Drug Administration, Center for Veterinary Medicine. Guidance For Industry. Bioequivalence: Blood Level Bioequivalence Study. December 2016. VICH GL52.

Cheers,
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. ☼
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nobody
Senior

2018-05-17 15:39

@ Helmut
Posting: # 18775
Views: 600
 

 Necessity of MD study based on expected accumulation

Vienna calling...

Have you switched to Animal Farm? All pigs are created equal? Nobody didn't get it... including me?

Can you elaborate on this a little more? Scheerans et al. showed that EMA is overly conservative, not really a surprise, or?

Kindest regards, nobody
Helmut
Hero
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Vienna, Austria,
2018-05-17 15:52

@ nobody
Posting: # 18776
Views: 629
 

 EEA = Armorica?

Hi nobody,

» Vienna calling...

Rightyright.

» Have you switched to Animal Farm? All pigs are created equal?

When I posted that I almost referred to Mr Orwell. :-D

» Can you elaborate on this a little more? Scheerans et al. showed that EMA is overly conservative, not really a surprise, or?

It isn’t. At the EUFEPS 3rd International Conference of the Global Bioequivalence Harmonisation Initiative last month in Amsterdam an entire session was devoted to this issue. Guess my opinion.
EMA reminded me of the indomitable village.

Cheers,
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. ☼
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nobody
Senior

2018-05-17 16:30

@ Helmut
Posting: # 18777
Views: 597
 

 EEA = Armorica?

» Guess my opinion.

Slides or it didn't happen.. 8-p

» EMA reminded me of the indomitable village.

https://www.youtube.com/watch?v=7WJXHY2OXGE

Kindest regards, nobody
Helmut
Hero
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Homepage
Vienna, Austria,
2018-05-17 16:40

@ nobody
Posting: # 18778
Views: 604
 

 EEA = Armorica?

Hi nobody,

» https://www.youtube.com/watch?v=7WJXHY2OXGE

One of my favorites. Also a rare example where Terry Gilliam performs (as Cardinal Fang). I have everything of MP still on VHS-tapes rotting away.

Cheers,
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. ☼
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