Biotech Values

[Shengli]

the Court finds no reason to doubt the FDA’s explanation
regarding its request for additional information relating to
impurities.
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Therefore, given the deferential
standard of review that this Court must accord the FDA’s
scientific determinations, the Court finds it unlikely that
Sanofi will succeed in its argument that the FDA’s approval of
generic enoxaparin is inconsistent with its past precedent.

3. FDA’s Determination that Sandoz’s ANDA has the
Same Active Ingredient as Lovenox
Finally, Sanofi argues that it is likely to succeed on the
merits because the FDA approved generic enoxaparin without
Opp’n Br. at 32 (“Omnitrope, unlike enoxaparin, was never
determined to have the ‘same’ active ingredient as the innovator
[RLD], and in fact had acknowledged differences in certain
respects. Thus, it was not approvable as an ANDA under 21 U.S.C.
§ 355(j)(2)(A). By contrast, FDA has determined that Sandoz’s
enoxaparin has the ‘same’ active ingredient as the listed drug,
Lovenox, because it has been adequately characterized and has met
the five criteria.”); Fed. Defs.’ Opp’n Br. at 33-34 (“In its
Premarin decision, FDA determined that it would not accept an
ANDA for a synthetic (laboratory-synthesized) version of Premarin
because the RLD was not adequately characterized. FDA stated,
however, that it could approve generic copies of Premarin if they
originated from the same natural source material (pregnant mares’
urine) and were subject to similar manufacturing controls. FDA’s
enoxaparin decision is consistent with its decision for natural
sourced Premarin because generic enoxaparin is derived from the
equivalent source material and is manufactured using a wellcontrolled
process.” (internal citations omitted)).
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sufficient evidence that Sandoz’s ANDA has the “same” active
ingredient as Lovenox as required by § 355(j)(2)(A). Sanofi
contends that in approving Sandoz’s ANDA, the FDA “ignored
voluminous scientific evidence demonstrating that until
enoxaparin is fully characterized, generic enoxaparin products
that do not use a manufacturing process that is equivalent to
[Sanofi’s] process will not be the same as Lovenox.” Pl.’s Mem.
at 33. It further asserts that the FDA failed to provide a
“rational explanation for its decision to disregard scientific
evidence that directly contradicts its administrative findings,”
and therefore is arbitrary and capricious. Pl.’s Mem. at 33-34.
The Court finds these arguments unavailing.
In its response to Sanofi’s citizen petition, the FDA
provided a detailed explanation regarding its determination that
an ANDA applicant for enoxaparin can demonstrate “active
ingredient sameness” by meeting five criteria, “each of which
captures different aspects of the active ingredient’s
‘sameness.’” AR 2879-80. In particular, the FDA found that an
ANDA applicant seeking approval for generic enoxaparin must
demonstrate: (1) equivalence of physicochemical properties, such
as molecular weight distribution and overall chemical
composition; (2) equivalence of heparin source material (i.e.,
heparin that is derived from porcine intestinal mucosa and that
meets USP monograph standards for Heparin Sodium USP) and mode of
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depolymerization (i.e., cleavage by alkaline ß-elimination of the
benzyl ester derivative of heparin); (3) equivalence in
disaccharide building blocks, fragment mapping, and sequence of
oligosaccharide species; (4) equivalence of in vitro biological
and biochemical assay results; and (5) equivalence of in vivo
pharmacodynamic profile based upon measurements of in vivo anti-
Xa and anti-IIa profiles. See AR 2888-900. The FDA also
provided an exhaustive response to the arguments raised in
Sanofi’s citizen petition, see generally AR 2904-21, including
Sanofi’s claim that the FDA should refrain from approving any
ANDAs citing Lovenox as the RLD unless, among other things, the
manufacturing process used to create the generic drug product was
deemed to be equivalent to Sanofi’s manufacturing process for
Lovenox. See AR 2905-13 (explaining why ANDA applicants for
enoxaparin do not need to demonstrate that they use the same
manufacturing process as Sanofi).