080: Improving Administration Method Consistency of Product-Specific Guidances for Chewable Tablets & Tablet Products With Chewing in Labeling

Statement of Purpose: Chewable tablets are an oral dosage form instructed to be chewed and then swallowed by the patient. There are also tablets (not strictly chewable tablets), for which several administration methods such as “chew,” “chew or swallow,” or “chew or disperse,” are observed from the labeling. The FDA draft guidance Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA (FDA draft guidance) recommends that if the reference listed drug (RLD) labeling states that the tablet must be chewed before swallowing, the product should be chewed when administered in bioequivalence (BE) studies. If the labeling provides an option of either chewing the product or swallowing it whole, the product should be swallowed whole with water in BE studies. Per preliminary review, administration of water is not always specified in the RLD labeling and several product-specific guidances (PSGs) of chewable tablets or tablets with chewing described in the labeling do not provide a specific administration method in BE studies. The objective of this work was to align the administration method recommended in PSGs for these products to the recommendations outlined in RLD labeling and the FDA draft guidance.

Description of Methods & Materials: A survey of the FDALabel database (https://nctr-crs.fda.gov/fdalabel/ui/search) was conducted using a filter search of “new drug application (NDA)” and “oral,” and key words (e.g., “chew,” “chewing”). The following information was collected from the FDALabel database: active pharmaceutical ingredients, drug products, dosage forms, and administration methods. A survey of PSGs for chewable tablet products and tablets which describe chewing in the labeling was conducted following FDALabel database search.

Data & Results: A total of 38 drug products that instruct patients to chew the tablet in the Dosage and Administration Section of the labeling were identified and the product labeling identifies these products as either chewable tablets (n= 33) or tablets (n= 5). Among the identified PSGs (n=26), three PSGs instructed chew the tablets or were silent on administration method in BE studies when RLD labeling recommended chew or swallow whole. Two PSGs were silent on the administration method when RLD labeling recommended chew the tablet with water. Two PSGs were silent on water after chewing in BE studies when RLD labeling recommended chew the tablet with or without water, or silent on intake of water. One PSG was silent on administration method and the RLD labeling was also silent on the administration method (e.g., no instruction on chewing or swallowing whole).

Interpretation, Conclusion or Significance: Administration methods of eight out of 26 PSGs were not aligned with the RLD labeling and the FDA draft guidance. These eight PSGs were recently updated to align the administration method recommended in PSGs with that described in RLD labeling and the FDA draft guidance, aiming to improve consistency with regard to the administration method of recommended BE studies for generic drug development.

Disclosures: This work reflects the views of the authors and should not be construed to represent FDA’s views or policies.