Bioequivalence and Bioavailability Forum

Hello Velupharm!

❝ But according to USFDA requirements, we have to submit the sprinkle studies

❝ done with the innovator's and test drug (if i am correct). But our study

❝ was passing with routine fed studies (innovator vs test) but failing on

❝ upper limits in the sprinkle fed study (innovator vs test).

Referring to the http://www.fda.gov/cder/guidance/5194fnl.pdf US-FDA Guideline:

III. RECOMMENDATIONS FOR FOOD-EFFECT BA AND FED BE STUDIES
B. Modified-Release Drug Products
2. ANDAs
In addition to a BE study under fasting conditions, a BE study under fed conditions should be conducted for all orally administered modified-release drug products.

So if you have done both fasting and fed studies (test vs reference) and demonstrated BE, you should get the approval. Only if the innovator makes a claim of BE (sprinkled vs intact) in his label, additionally:

VI. OTHER CONSIDERATIONS
A. Sprinkles
In ANDAs, BE of the test to the RLD is demonstrated in a single dose crossover study. Both treatments should be sprinkled on one of the soft foods mentioned in the labeling, usually applesauce. The BE data should be analyzed using average BE and the 90 percent CI criteria should be used to declare BE. If there are questions about other foods, the design, or the analysis of such BE studies, the sponsors and/or applicants should contact the Office of Generic Drugs.

After reading the paragraph a couple of times, I think you are correct:
If the innovator makes a claim of BE (sprinkled vs intact), then you should perform a study (necessarily in fed state?) test vs reference, both products sprinkled.

Since you failed to demonstrate BE in this study, IMHO it should still be possible to include a statement like 'The drug product must not be opened and it's contents sprinkled on soft food, e.g., apple sauce.' in your label.

Actually my first answer was coming from a too European point of view in your case (stupid me, you were referring to US-FDA), because in the EU a 'sprinkled' study is not mandatory for approval - even if the innovator makes such a claim in his SmPC (the European label).
In the EU generally we start with a labeling given above, and later on (optionally!) go for a 'line extension' of our product, which includes BE of 'sprinkled' vs 'intact' (no more testing against the innovator, because our product is already approved).

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Edit: Link corrected for FDA’s new site. [Helmut]