Replies to post #111616 on Biotech Values

[y3maxx]

Biomaven,

""On November 2, 2007, the FDA acknowledged, in a letter to Amphastar from the Office of Generic Drugs, that Amphastar had met the FDA’s five “sameness” criteria and therefore had demonstrated its enoxaparin’s sameness with Lovenox® in its ANDA.""

Mouton,

""I checked the docket for the case and don't see an exhibit of said letter.""

Dew,

...If true, why is Amphastar proceding like this?

tia

y3

[dewophile]

by all accounts it seems to me the FDA back in 2006 was going to set a relatively low bar for generic approval of lovenox, and telegraphed (i don't knwo about the call per se) to amphastar (and probably teva) that they met sameness and approval was around the corner. then a couple things happened. fist the CP from sanofi pointing out the vagaries of the manufacturing process that go well beyond Xa/IIa equivalence (e.g. anhydrous ring), a series of publications hit around that time (one can find the citations on this board) examining lovenox knockoffs and how they can potentially have meaningful clinical differences, including differing immunogenic profiles, and then the bar was suddenly set higher, and all applicants were asked for immunogenicity testing. note this request came in before the heparin crisis hit, but that added another layer to the approval process

that amphastar did not include the letter as an exhibit is curious - i have a hunch it will say they met sameness and does not spell out the 5 criteria - as you point out this would be hard to believe - but that amphastar took the liberty of extrapolating that since NOW the fda requires 5 criteria for sameness they must have met those criteria back in 2006-7

it also seems immunogenicity is the biggest hurdle - curious that amphastar's response to the immunogenicity request came 5-6 months prior to MNTA's according to the brief - that all but shoots down TEVA's claim that the delay in assessing immunogenicity in their application likely had to do with timing of the response relative to MNTA (but we already knew that since well over a month has passed and MNTA confirmed they met immunogenicity hurdle over a year prior to approval). that they have purified the product carries little weight regarding immunogenicity since it is the immunogenic response to the byhproducts of the depolymerization process that is key, not ensuring minute quantities of impurities are introduced extraneously

i think the FDA response to this petition will make for an interesting read

[dewophile]

Note that the complaint was amended between the original filing and the December 22 fling. The original complaint only alleged the various improper FDA behaviors relating to inspections and detention of supplies, etc. and only sought an injunction against that behavior. The amended complaint now adds the allegations about sameness and asks that the FDA be directed to approve the Amphastar ANDA.

actually "sameness" appears in the original complaint. item 23, page 5:

http://www.fdalawblog.net/files/lovenox---amphastar-complaint.pdf

23. Amphastar's Abbreviated New Drug Application remains pending despite reaching "sameness" (a prerequisite for FDA generic drug approval) on november 2,2007...

notably absent is any claim of having met the 5 criteria for sameness

the fact they omitted stating they met the 5 criteria when referencing the nov 2 2007 letter in the original complaint further adds doubt that they actualy met the 5 criteria in 2007. so i have to stand by my original assertion that they extrapolated meeting the 5 criteria based upon a looser definition of "sameness" in 2007