Detailed analytical information on Premarin's composition is the necessary basis for adequate characterization of the product. Obtaining this information is feasible. The constituents of Premarin are small molecules that can be fully characterized by analytical chemistry, unlike the macromolecular constituents of most biological products, which are difficult to fully characterize due to biologic variability. It is desirable that the components present in Premarin at or above 0.1% be characterized and their biological activities determined.
It has been argued that DHES cannot be considered an active ingredient of Premarin because its presence in and percent composition of the formulation are not specifically controlled during the manufacturing process. Wyeth-Ayerst has submitted data demonstrating that DHES is present at about 4.4% of label claim with a range of 4.0 to 5% (based on ten lots of 0.625 mg Premarin tablets). It is desirable that any active ingredients, once identified, be controlled during the manufacturing process.
I think this is the key passage from the Premarin release from the FDA. MNTA has shown what is possible. No other company could do this back in Premarin's day (although the FDA declares here that it was possible). Given this, I don't see why the FDA would require any less now, particularly since MNTA has proven that it is possible.
So I think what we are left with is can Teva characterize in this manner? The answer from all the available sources is no.
What we don't know if Teva has, although this would be a long shot, submitted a new application with some acquired or developed technology that they picked up along the way. However, I think this is even a bigger long-shot because brokers and analysts have not been given any information, at all, at to Teva's capacity to fully characterize. They are still under the belief that Teva is still working with what it was working with pre-patent invalidation.
Anyways, food for thought. We will see when we see.
Tinker
