RockRat, in regard to lovenox, I've gone through the Aventis Citizen Petition you linked to, pulled up the Teva response thereto, and went through the FDA monograph. I do not read it as a chemical expert but in regard to comparison of the relevant parties to ascertain what is really going on.
I have to say that I agree with you on the rigidity of the requirements that the FDA put forward. This is summed up in the monograph that emphasizes a "sophisticated set of analytical methods for analytical characterization."
In particular, I find persuasive part of the Aventis Citizen Petition that the FDA actually rejected, that the manufacturing process for Lovenox has to be identical.
Clearly the manufacturing process does not have to comport with that used by Aventis, however, to obtain the sort of detailed equivalence that the FDA is looking for (and they cite the 4 brand names of LMWH products that have been approved with distinct names because the small differences from each of their respective manufacturing processes creates real and substantive differences in characteristics) you either have to have the same manufacturing process, or you have to have detailed characterization of the molecule sufficient to reverse engineer the drug to sufficient exacting standards. And these standards are exacting (again referring back to the 4 distinct brand names of LMWH, as small differences create real and material substantive behavior of the drug).
It is clear that Teva, in its application (most of the work was done on this application by Teva back in the late 1990s, early 2000s, pre-dating MNTA's more sophisticated methodologies) stuck primarily to the industry standard for replicating generic drugs, and is arguing that the degree of sameness need not be exacting, and can be similar enough. That full characterization is neither possible nor necessary, and that sufficient "sameness" (quoting from small molecule definition of the word) is what is required and sufficient.
The FDA made clear in its response to Aventis that 100% characterization was not necessary, and exact chemical replication was not necessary. Teva prevailed on this issue. However, in the FDA's approval of m-enoxaparin and the criteria that it created to set the standard, it basically handed Aventis a victory by setting the barriers so high in that MNTA did not need to fully characterize the molecule (as Aventis argued), but it nevertheless is hard to imagine how you could sufficiently recreate and characterize the molecule with the required rigidity without either (1) utilizing the exact manufacturing process, or (2) fully characterizing the molecule, at least to a very great degree. I.e, although the FDA largely rejected Aventis's Citizen Petition, the FDA's final standards on generic lovenox are such that Aventis practically won on not all, BUT much of what it was arguing for.
Understanding and recreating the known "active" ingredients itself, demonstrating similarity, and in vivo pharmacodynamic profile is not going to cut it. And that is what Teva has done.
Not bad for a lay person. Is that your understanding of the issue Rockrat? Dew?
Given this analysis (if accurate) it does not seem possible that Teva could meet the criteria, as its processes are not exacting enough. The FDA made clear that exact characterization is not necessary, BUT so much of the complex details are required to be recreated correctly that one could not manage to do it by chance as they go about recreating the core aspects of the drug as Teva has done.
Thanks for any input.
Tinker
