The recommendation, part of draft guidelines issued last week, is designed to ensure that capsule-formulated drug products that are approved for mixture with soft food to aid delivery perform correctly and can be properly absorbed.
The Food and Drug Administration (FDA) said it: “Recognized the specific importance of a maximum bead size limit for modified-release products, where unintentional chewing of beads may lead to pharmacokinetic differences.”
The agency suggested that considerable “taste and performance issues” may arise from accidental chewing and that these again could result in non-compliance and decreased therapeutic efficacy.
The draft guidance also flags up bioequivalence as an area likely to be affected by differences in bead size.
For NDA submissions the agency calls on manufacturers to undertake bioavailability studies to prove that drug’s mixed with food perform in a manner consistent with non-mixed product as a condition of gaining “sprinkle” approval.
And for ANDAs said it wanted generics manufacturers to carry out bioequivalence tests for modified-release products but deemed such assessment unnecessary for immediate-release products.
The recommendations are roughly in keeping with the results of research published in the AAPS PharmSciTech Journal last year.
In the paper “Analysis of Bead Sizes for MR Capsules Labelled for Sprinkle,” lead author Laxma Nagavelli advocates a maximum bead size of 1.5mm, based on a review of 436 products approved for “sprinkle delivery” by the FDA at the time.