FDA issued a draft guidance for industry on Jan. 18, 2011, about the size of beads within drug products labeled for sprinkle. Beads are often included in capsule products that contain labeling that indicates patients can break the capsule and sprinkle its internal beads on soft foods to swallow (without chewing) as an alternative administration technique. According to the document, this type of administration is common with extended- or delayed-release characteristics. The concern lies in whether patients can swallow the beads with the soft foods without chewing the product. If the beads are chewed, the drug product may be absorbed and released too quickly into the body.
The guidance specifically calls for a maximum bead size of 2.0 mm. This is based on approved product information and human studies that demonstrate food is chewed to approximately 2 mm in median particle size before swallowing. “We recognize the specific importance of a maximum size limit for modified-release products, where unintentional chewing of beads may lead to pharmacokinetic differences. It is our belief, however, that maintaining a consistent maximum size of beads for all drug products labeled for sprinkle is prudent. Taste and performance issues that may arise from inadvertently chewing beads labeled for sprinkle may lead to noncompliance and decreased drug product efficacy,” states the draft document.
The guidance also provides current FDA thinking on delivering capsule beads via an enteral feeding tube as well as its recommendations on bioavailability and bioequivalence.
In terms of submission information, the draft guidance recommends that bead-size distribution be provided in a common technical document (CTD) application, specifically in section 3.2.P.3.3 (Description of Manufacturing Process and Process Controls) or in section 3.2.P.5.1 (Specification). The maximum bead size can be provided in the CTD 3.2.P.1 (Description and Composition of the Drug Product) section or 3.2.P.4 (Control of Critical Steps and Intermediates) section.
The draft guidance does not apply to bead products already on the market, but only to applicants of new drug, abbreviated new drug, or new biologics licensing applications (NDAs, ANDAs, BLAs). “Currently approved NDAs, ANDAs, or BLAs that contain beads that are greater than the recommended 2.0 mm need not modify their product specifications (unless the product has issues that are affecting public health),” states the draft guidance. However, an ANDA that references a currently approved reference listed drug (RLD) may propose a bead size equal to or less than the size of the bead used in the currently approved RLD, according to the document. Such data should be provided to support the size(s) of the beads in the ANDA product within a CTD submission.
Comments on the draft guidance are due within 90 days of the document’s publication.