I read a great article by Joanne S. Egolvitch in the RAPS Regulatory News this morning about elimination of Citizen Petitions for TE ratings for 505(b)(2) products (here).  The issue centers on the FDA’s (kind of wonky) requirement that 505(b)(2) applications with minor formulation changes requiring them to be submitted as an NDA also require a petition to be submitted to the Agency for action on the assignment and issuance of a TE code.

I’d raved on this issue in a previous blog; I don’t want to bore you with the specifics as they appear here.  This was an easy process while I was at the FDA but somehow (like ANDA suitability petitions) the FDA almost stopped responding to them.  The people that suffer are, in the end, the patients that need these drug products.

After reading Joanne’s article, I agree with all of the industry comments that she outlined with two exceptions.  First, the Generics Access Project (GAP), unless I misunderstood their position, was reported by RAPS to suggest “that FDA allow manufacturers using the 505(b)(2) pathway for complex generics be able to request an automatic TE rating upon approval to improve the availability, sustainability, and substitutability of complex generics.”  The issue of automatic TE rating suggests to me that all (b)(2) applications for complex products would receive a TE rating.  There is obviously additional information that may make the product not found to be TE to the RLD cited in the application.  If GAP is suggesting that there may be cases in which the TE rating based on the information in the NDA would result in a “B” rating because the FDA has a safety or efficacy issue with the drug, like a change in formulation that might not be considered appropriate for a specific patient population, then I am in line with the concept that the FDA should be ready to issue the TE code regardless of what it might be at the time of approval of the application.  If not, then each application should be judged on its own merit, but I agree that a TE code should be assigned at the time of approval.

The second issue that I take exception with is the suggestion, reported in the article in RAPS, that the “FDA should not remove TE ratings from the Orange Book once they are assigned, even if a drug becomes single-source.”  This goes against the definition of the TE rating relative to its assignment as the only time a TE rating makes sense is if there is another product that it is being compared to (a product with the same dosage form, strength, route of administration, and active ingredient as well as for the same conditions of use as that of the RLD).  Once a product becomes “sole source,” since there is no comparator, I believe that the FDA should continue its current practice of removing TE ratings for sole-source drugs.  Once another comparator is approved, then the process starts over again and a TE rating will depend on the information in the new application referencing the RLD or sole-source product.  There may be an argument to be made that a product that appears in the discontinued section of the Orange Book should have its TE rating revived once the FDA approves a product citing the discontinued product as the RLD.  However, since the product may be withdrawn from the market, that should happen only when the RLD is brought back onto the market, at least in my opinion.

The comments were submitted in reference to the July guidance titled Evaluation of Therapeutic Equivalence, which can be found here.