E-DRUG: bioequivalence

e-drug
1

E-drug: bioequivalence
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Dear Colleagues,

I have been confronted here in Colombia with the issue of the general
quality of generic medications, specially those relating with
bioequivalence of selected medicines like ampicillin.

Extrapolating from the clinical trial field, is there a general
consensus in this setting on when differences are close enough that
equivalence is accepted? and its related power and sample size issues
for statistical significance testing, to minimize false negative (type
II) errors?

Thanks in advance,

Rodolfo J Dennis, MD
Head, Clinical Epidemiology & Biostats Unit
Javeriana University, Bogota
Colombia
Email: rdennis@javercol.javeriana.edu.co

---note from the moderator:
WHO has published official guidelines on this: see WHO Technical Report
Series No 863: 34th report of WHO expert Comm on specifications for
Pharmaceutical preparations. WHO, Geneva, 1996.

In annex 9 (page 114-139): Multisource (generic) pharmaceutical products:
guidelines on registration requirements to establish interchangeability,
WHO defines 3 levels of "equivalence":

1. pharmaceutical equivalence (same route, same molecule, same standard)

2. therapeutic equivalence: 1 + "afteradministration in the same molar
dose, their effects, with respect to efficacy and safety, will be
essentially the same, as determined from appropriate studies (bioequi-
valence, pharmacodynamic, clinical or in vitro studies).

3. bioequivalence: 2 + "and their bioavailabilities (rate and extent of
availability), after administration in the same molar dose, are similar
to such a degree that their effects can be expected to be essentially
the same."

These different 'levels of confidence' in 'equivalence' then must be
interpreted at national level by Drug Regulatory Authorities.

Oral ampicillin is no longer recommended by WHO (replace with
amoxicillin)

Oral amoxicilline preparations are not on the list of products that might
be subject to bioavailability problems in The Netherlands or Germany.
Opinions, however, differ from country to country.

Wilbert Bannenberg, E-drug moderator
Email 73377.3055@compuserve.com

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