Bioequivalence and Bioavailability Forum

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

posted by Helmut  – Vienna, Austria, 2018-05-10 15:55 (2170 d 15:49 ago) – Posting: # 18760
Views: 3,175

Dear all,

the EMA requires multiple dose studies of prolonged release products if the mean AUC_τ–∞ of both products after a single dose is >10% of AUC_0–∞,^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.

Kudos. Accumulation <2 (AUC_τ–∞ <50% of AUC_0–∞) is considered negligible.

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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.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


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Complete thread:

• Necessity of MD study based on expected accumulationHelmut 2018-05-10 13:55 [Regulatives / Guidelines] 
  • Necessity of MD study based on expected accumulation nobody 2018-05-17 15:39
    • EEA = Armorica? Helmut 2018-05-17 15:52
      • EEA = Armorica? nobody 2018-05-17 16:30
        • EEA = Armorica? Helmut 2018-05-17 16:40