Biotech Values

[Mpower]

jbog,

I would urge you to review the FDA document re: "Establishing Active Ingredient Sameness for a Generic Enoxaparin Sodium, a Low Molecular Weight Heparin"

Specifically, the high-thresholds outlined that must be met ( keeping in mind that Teva/Amphastar who had a 2 year lead over MNTA in submitting their mL application did not receive a nod). The approach articulated by the FDA is in-line with MNTA's approach, the level of sophistication needed requires MNTA's characterization platform...

It will take time for market participants to fully understand the implications of the FDA approval on the development of generics complex molecules -- in other words, the ? mark you outline is not really a ? mark, it is settled....

Because of the complexity described above, FDA found that the criteria typically used to approve generic drugs (e.g., compendial requirements) were inadequate by themselves to characterize the “sameness” of enoxaparin sodium, and that additional criteria were needed. To address this issue, FDA developed a set of rigorous and overlapping criteria to be used in the approval of generic enoxaparin sodium (See Table 1).

Table 1. Criteria Used for Sameness Determination of Enoxaparin Sodium
1. Equivalence of heparin source material and mode of depolymerization
2. Equivalence of physiochemical properties
3. Equivalence in disaccharide building blocks, fragment mapping, and sequence of oligosaccharide species
4. Equivalence in biological and biochemical assays
5. Equivalence of in vivo pharmacodynamic profile

The first three criteria are used to ensure that the heparin source material, the chemical reaction used in the manufacturing process, and the structure (the distribution of molecular weight, chemical composition and sequence) of the active ingredient, enoxaparin sodium, in the generic drug product is equivalent to that in the brand name counterpart, Lovenox. The fourth and fifth criteria are used to ensure that the generic enoxaparin sodium has the same degree of anticoagulant activity as Lovenox. Together, these criteria ensure that a generic enoxaparin sodium will have the same active ingredient as Lovenox.

Using these criteria, FDA has approved a generic version of Lovenox (enoxaparin sodium injection). FDA determined that Sandoz demonstrated that all requirements for generic drug approval were met, including that its generic enoxaparin sodium has the same active ingredient as the brand name product, Lovenox.