Replies to post #111653 on Biotech Values

[zipjet]

imo that leaves only immunogenicity and supply chain issues as obstacles for amphastar, and presumably only immunogenicity for teva

Supply chain. I suspect that this issue is really about qualifying the feed stocks used. Over time there will be shifts in the material supplied by the same supply chain. So testing of the supply is necessary as the product shifts or suffers contamination. MNTA has an advantage but not a lock-out on this factor.

Immunogenicity. This comes up in every case. It caused the delay of mL and still delays tL.

So when will Teva get this right? Why was MNTA able to do this and TEVA not?

Missing November 2007 FDA letter. I will bet that if/when the letter is public that it describes clearly Amphistar's deficiency. That is why the positive content of the letter was described and the letter itself was not attached as an exhibit.

ij

[DewDiligence]

From the FDA’s own statement issued on the day it approved NVS/MNTA’s Lovenox (#msg-52582225):

The chemical reaction used to make enoxaparin sodium results in oligosaccharide fragments of distinctive sizes and sequences. It also modifies the chemical structure of sugar residues at both ends of the fragments. Such chemical modifications may affect the activity of this drug . If a manufacturer wants to make a generic enoxaparin sodium, it has to design a manufacturing process that is capable of reproducing these distinct features of the drug. Otherwise, a generic enoxaparin sodium might not behave in the same way in the body as the brand name counterpart, Lovenox.

Thus, demonstration of “sameness” for enoxaparin sodium requires “state-of-the-art” analytical methods to show that the structural features of oligosaccharides in the generic enoxaparin sodium are equivalent to those in Lovenox.

In other words, the FDA’s five criteria for “sameness” (equivalence of heparin source material and mode of depolymerization; equivalence of physiochemical properties; equivalence in disaccharide building blocks, fragment mapping, and sequence of oligosaccharide species; equivalence in biological and biochemical assays; and equivalence of in vivo pharmacodynamic profile) are merely a starting point—they are necessary but not sufficient to obtain FDA approval for a generic version of Lovenox.