Re the five criteria for sameness.
There is some detail about the chronology in the Sanofi v. FDA December 13, 2010 motion for summary judgment. From the "State of Undisputed Material Facts in Support of Motion for Summary Judgment. References to the AR are, I believe, references to the FDA administrative record, which is listed on the docket sheet but is restricted and not available to the public.
Case 1:10-cv-01255-EGS Document 38-2 Filed 12/13/10
FDA’s Analysis of Active Ingredient Sameness for Enoxaparin
18. Sandoz submitted an ANDA for generic enoxaparin on August 26, 2005.
AR 4167.
19. Prior to Sandoz’s submission of its ANDA, the Office of Generic Drugs
(OGD), located within FDA’s Center for Drug Evaluation Research (CDER), developed five
criteria for assessing active ingredient sameness in generic enoxaparin. AR 3836, 3840. Those
criteria include: (i) equivalence of physicochemical properties; (ii) equivalence of heparin source
material and mode of depolymerization; (iii) equivalence in disaccharide building blocks,
fragment mapping, and sequence of oligosaccharide species; (iv) equivalence in biochemical
assays; and (v) equivalence of in vivo pharmacodynamic profile. AR 2888.
20. Beginning in 2004, scientists at FDA’s Office of New Drug Quality
Assessment (ONDQA) expressed their disagreement with OGD’s five-criteria approach.
ONDQA’s scientists, including Dr. Ali Al-Hakim, an expert on heparin and heparin-based
products, argued that it was impossible to demonstrate active ingredient sameness for enoxaparin
without completely characterizing all of enoxaparin’s oligosaccharide chains, including sequence
elucidation in a molecule-to-molecule comparison. AR 3714-15, 3840. ONDQA’s scientists
further contended that, because enoxaparin contains a unique mixture of oligosaccharides, they
were unable determine which components of the mixture contributed to enoxaparin’s activity.
AR 3842. The scientists therefore concluded that OGD’s five criteria were insufficient to
demonstrate active ingredient sameness, and that OGD’s methodology was contrary to law and
FDA policy. AR 3842.
21. On July 20, 2010, Dr. Keith Webber, Deputy Director of the Office of
Pharmaceutical Science within CDER, announced in a intra-agency memorandum that OGD’s
five-criteria test was a “valid approach for determining enoxaparin sameness for purposes of
ANDA approval.” AR 3836. Dr. Webber acknowledged, however, that enoxaparin is a
heterogeneous mixture with unique chemical properties, and that there may be “unique
challenges” in “pinpointing” its pharmacological activity. AR 3837-45.
V. FDA’s Requirement that ANDA Applicants Conduct Immunogenicity Testing
22. In the fall of 2007, Dr. Janet Woodcock, then the Acting Director of
CDER, determined that, in addition to satisfying OGD’s five criteria for active ingredient
sameness, ANDA applicants were required to conduct immunogenicity testing to demonstrate
that their generic products would not produce a greater immunogenic response than Lovenox.
AR 3853.
23. Dr. Woodcock noted that Lovenox is associated with heparin-induced
thrombocytopenia (HIT), a major immunological adverse event that is often life-threatening and
can be fatal. AR 3848-49, 3852.
Market Data 
Markets 
AI
