At our CMC EOP2 meeting w/FDA we posed the following 2 questions for development of our IR oral tablet product which has 5 strengths (10-20-30-40 and 50 mg) that use a common granulation. 1) We proposed using only a blue colorant for all table strengths and would differentiate by applying a unique ink tablet marking for each strength and 2) we submitted a stability bracketing proposal in accordance with ICH Q1D where we would bracket the intermediate 20-30-40 mg strengths and only test 3 batches of the lowest (10 mg) and 3 batches of the highest strengths (50 mg).
FDA's response to #1 was that since we did not provide a picture or other visual side-by-side comparison of the intended tablet sizes and markings FDA could not comment. FDA also suggested using different colors, shapes, or other means to further differentiate the tablets. FDA's response to #2 was that our bracketing proposal was acceptable.
So now we plan to accept FDA's suggestion and implement different tablet colors when we manufacture our Registration batches. But can we assume the stability bracketing proposal is still acceptable to FDA now that we are introducing different colored tablets? We've decided to add one batch of each intermediate strength (20-30 and 40 mg) to the stability program since this will be the first time using these new colors. We will also re-validate any analytical methods if it is determined the new colors cause any interference. Is it necessary to run this "new" stability strategy by FDA again for their agreement, or is adding the one batch of each intermediate strength to the program a conservative enough approach to not have to get FDA agreement?
Thanks in advance for any feedback.
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Tom Stothoff
Senior Director, Regulatory Affairs CMC
Chicago
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