Bioequivalence and Bioavailability Forum

Dear Phani,

please search in the future.

❝ Is phenotyping/genotyping mandatory in a parallel design of study, this is stated in EMEA guidance.

No, it is not mandatory - but highly advisable. If you have the slightest hint of genetic polymorhism, do it. Remember, that in a parallel design the treatment effect is based on a between-subject comparison. What if you have by chance one slow metabolizer in one group of subjects and none in the other? The treatment effect will be biased.

I would not phenotype/genotype only if

• the drug is excreted unchanged, or
  
• you have - well documented - evidence that the metabolic pathway is not subjected to polymorphism.

❝ Isn't the procedure cumbersome?

Phenotyping, yes. Genotyping, no. The former needs administration of a model drug, collection of (24h-) urine, having a validated method, relying on an accepted metabolite/parent-ratio,… The latter is technically easier (collection of just one blood sample), but requires adherence to additional legal requirements in some countries.

For a CRO genotyping is the method of choice. From one blood sample the subject can be genotyped for all expressing alleles. In other words, you get information about all phenotypes - contrary to simple phenotyping (only one specific pathway).

BTW, see this bad case.