FDA drew a line in the sand in finalizing a guidance limiting orally disintegrating tablets to a 30-second dissolution time and 500 mg weight, despite industry arguments that such restrictions would discourage development of ODTs.

The December ¹ guidance does provide some leeway, however, provided the sponsor can justify deviations from the recommended dissolution time and weight.

Industry contended that the 2007 draft guidance was more restrictive than necessary (² [A#00690340010], p. 20). Sponsors requested the time limit be extended to 60 seconds and complained that the weight requirement was not justified scientifically.

Orally disintegrating tablets were originally developed to address potential issues of patient compliance, FDA noted, but newer products exhibit "wide variation in product characteristics from the initial products," including larger sizes and longer dissolution times.

A review showed a large majority of products - representing different manufacturing technologies, tablet sizes, weights and disintegration strategies - had dissolution times of 30 seconds or less, supporting FDA's assertion that 30 seconds is an achievable goal.

The agency updated the definition of an ODT product based on the intention of the original definition and experience with new drug applications and ANDAs. According to the final guidance, ODTs should "be considered solid oral preparations that disintegrate rapidly in the oral cavity, with an in-vitro disintegration time of approximately 30 seconds or less, when based on the USP disintegration test method or alternative."

A willingness to compromise on time and weight as recommended at a July advisory panel was evident in the discussion section of the draft (³ Also see "“Difficult” Bioequivalence Issues Make Limited Progress At Advisory Cmte." - Pink Sheet, 28 July, 2008., p. 28). "Although the value of 30 seconds is given as a desired result, it is not intended to represent an arbitrary distinction between and ODT and some other tablet form," FDA states.

FDA also urges consideration of the effect large tablets have on patient safety and compliance - echoing GlaxoSmithKline's comments on the draft guidance - and suggests any tablet weighing more than 500 mg should be justified based on product performance.

One product that may have been impacted by the release of the guidance is GSK/Eurand's EUR-1048, a taste-masked ODT version of an undisclosed GSK drug. FDA issued a complete response letter for the NDA in late 2008. GSK resubmitted Dec. 24 and expects agency action in 60 days.

- Becky Jungbauer (r.jungbauer@elsevier.com)

FDA Finalizes ODT Guidance, Sticks To More Restrictive Recommendations

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