On January 13, 2015, FDA denied an ANDA suitability petition requesting a change in dosage form from Ibuprofen Chewable Tablets, 100 mg to an Orally Disintegrating Tablet of the same strength (here). As you know, an ANDA product must be the same as the reference listed drug (RLD) in dosage form, strength, active ingredients, and route of administration, unless an ANDA suitability petition (also referred to as a 505(j)(2)(C)) petition) is approved for the change. You may only petition for a change in strength, dosage form, route of administration, or change in active ingredient in a combination product (as long as the proposed active ingredient is of the same therapeutic category and there is a known equipotent dosage relationship between the RLD ingredient and the proposed ingredient). If the Agency determines that the change you propose does not pose questions of safety or efficacy, then the petition must be approved. A petition must be denied if FDA determines that clinical safety and/or efficacy studies must be required to assure the safety and efficacy of the proposed changed product.
Nobel Laboratories of Austin, Texas petitioned the FDA in November 2012 asking that an orally disintegrating form of ibuprofen be permitted to be submitted as an ANDA. FDA denied the request and stated that:
“There are no currently approved ibuprofen orally disintegrating tablets. Therefore, there are no safety data especially regarding local (oral) safety or tolerability for this formulation that remains in prolonged contact with the buccal mucosa.”
Because the decision on the change in dosage form found that safety studies were needed, FDA did not need to evaluate the issue of whether the provisions of the Pediatric Research Equity Act (PREA) would be triggered by the request. (Remember- PREA requires the study of drug products in pediatric patients for certain changes in drug products or new NDAs. As far as ANDA suitability petitions are concerned, PREA must be addressed in requests to change dosage form route of administration or ingredient, but it is not applicable to proposed changes in strength.)
The FDA has Guidance on orally disintegrating tablets that states that, in order to be considered orally disintegrating, the product must dissolve in the mouth within 30 seconds. Orally disintegrating products are typically designed so they may be taken without water and usually swallowed as they dissolve. It is interesting that FDA chose to raise a safety issue when ibuprofen is available not only in a chewable tablet form (don’t know how long it takes to chew up and swallow such a product), but the product is also available in a suspension dosage form, which must reside in the mouth for some period of time, and one would assume that, due to the suspension’s viscosity, there must be some residue left behind. Anyway, FDA must have its reasons, and the Agency’s decision will stand unless the petitioner files a petition for reconsideration. The firm also always has the option of submitting a 505(b)(2) application for the proposed orally disintegrating product that includes information on the safety question raised in the petition.
We have seen that, not only is it taking longer to get a petition reviewed and acted upon (Lachman has some petitions awaiting FDA action for more than 6 or 7 years), but the decision making on petitions appears to be getting more conservative. I actually thought this petition would sail through the process. Just goes to show you that even I, the first chairman of FDA’s ANDA Suitability Petition Committee some 30 years ago, can get fooled by some of FDA’s actions today.