Bioequivalence and Bioavailability Forum • Meal, Posture, Age Impact on BE and Study Requirement

Alpesh Ramani
☆

Ahmedabad, India,
2011-10-18 16:12
(5369 d 11:02 ago)

Posting: # 7513
Views: 2,662

Meal, Posture, Age Impact on BE and Study Requirement [Regulatives / Guidelines]

Dear All,

It has been learned so far that age, BMI, posture, composition of meal, etc should be uniform as strictly as possible because we measure only PK not efficacy. Thus by maintaining uniform conditions except Test/Reference we can identify formulation difference between test and reference in BE study.

It is recommended by regulatory authorities to prove the bioequivalence in fed state (Fed BE Study) in addition to fasting state (Fasting BE Study), when the drug is having food effect/ modified release formulation. This may be because to ensure the BE and thus therapeutic equivalence in fed conditions.

So, apart from fast/fed study is it not required to prove the BE with respect to other restrictions like different postures, abnormal BMI, old/child population ?

And if it is not required to conduct such studies why only fed study is being recommended ?

Keep answering.

—
Alps

Helmut
★★★

Vienna, Austria,
2011-10-18 17:57
(5369 d 09:18 ago)

@ Alpesh Ramani
Posting: # 7516
Views: 2,146

BE model: healthy subjects

Post reply

Dear Alps!

❝ So, apart from fast/fed study is it not required to prove the BE with respect to other restrictions like different postures, abnormal BMI, old/child population ?

❝

❝ And if it is not required to conduct such studies why only fed study is being recommended ?

See EMA’s current BE GL (Section 4.1.3 Selection of subjects):

The subject population for bioequivalence studies should be selected with the aim of permitting detection of differences between pharmaceutical products. In order to reduce variability not related to differences between products, the studies should normally be performed in healthy volunteers unless the drug carries safety concerns that make this unethical. This model, in vivo healthy volunteers, is regarded as adequate in most instances to detect formulation differences and to allow extrapolation of the results to populations for which the reference medicinal product is approved (the elderly, children, patients with renal or liver impairment, etc.).
(my emphases)

It’s a model considered to be adequate to extrapolate to other populations. Fed studies required for MR do not reflect the clinical situation as well (who is able to ingest the high-fat high-calory breakfast on a daily basis?) but are expected to challenge the formulation most (e.g., dose dumping, delayed release).

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

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