981 F. Supp. 2d 38
D.D.C.2013Background
- Cumberland marketed Acetadote (intravenous acetylcysteine); original formulation contained inactive ingredient edetate (disodium edetate) which Cumberland later determined unnecessary for stability.
- FDA approved Acetadote in 2004 subject to postmarketing studies, including study of edetate’s role; Cumberland’s study found edetate unnecessary and in 2010 submitted and obtained approval for a reformulation without edetate, then withdrew the original formulation from the market.
- A third-party citizen petition (Leydig) and a petition from Cumberland sought determinations that the edetate-containing formulation was not withdrawn for safety or effectiveness reasons, because an ANDA (InnoPharma) referenced the withdrawn formulation.
- FDA staff analyses (including Surveillance and Gastroenterology Division reviews) produced differing views; after reconsideration the FDA concluded the original edetate formulation was not withdrawn for safety reasons and granted a waiver allowing InnoPharma’s ANDA referencing the edetate formulation.
- Cumberland sued under the APA alleging the FDA’s denial of its petition and approval of InnoPharma’s ANDA were arbitrary, capricious, and contrary to law; the district court reviewed the administrative record and granted summary judgment to the FDA.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Whether original edetate-containing Acetadote was withdrawn for safety reasons | Cumberland: FDA’s earlier postmarketing request and some staff reports show safety concerns; withdrawal was safety-motivated | FDA: record evidence (adverse-event ambiguity, other edetate-containing products, internal review) supports conclusion withdrawal was not for safety reasons | Court upheld FDA: decision rational and supported by record |
| Whether FDA properly considered other edetate-containing products and adverse-event reports | Cumberland: FDA improperly relied on other products and inconclusive adverse-event data | FDA: comparison to other marketed edetate products and inconclusive reports are relevant circumstantial evidence; multiple rationales supported decision | Court: considering the whole record, these factors were legitimate and not arbitrary |
| Whether FDA permissibly waived inactive-ingredient parity for ANDA (21 C.F.R. § 314.99(b)) | Cumberland: waiver improper because InnoPharma’s product could be less safe; FDA should have required demonstration of no reduced safety | FDA: statute disallows approval only if inactive ingredient is shown to be unsafe; edetate is not a preservative/buffer/antioxidant so waiver consistent with law and regulations | Court: upheld waiver; FDA complied with statutory/regulatory standard (only disallow if unsafe) |
| Deference to agency scientific and mixed-record judgment | Cumberland: agency reversal and internal disagreement show arbitrary action | FDA: agency decisionmaker’s reasoned explanation and expertise merit deference despite staff disagreement | Court: applied highly deferential arbitrary-and-capricious review and found FDA’s path reasonably discernible and supported |
Key Cases Cited
- Motor Vehicle Mfrs. Ass'n v. State Farm, 463 U.S. 29 (agency must examine relevant data and articulate rational connection between facts and decision)
- Am. Horse Prot. Ass'n v. Yeutter, 917 F.2d 594 (D.C. Cir. 1990) (highly deferential review; presume validity of agency action)
- Serono Labs., Inc. v. Shalala, 158 F.3d 1313 (D.C. Cir. 1998) (ANDA statutory framework and deference to FDA on bioequivalence/related issues)
- Schering Corp. v. FDA, 51 F.3d 390 (D.C. Cir. 1995) (FDA judgments about safety/efficacy fall within agency expertise and merit deference)
- IMS, P.C. v. Alvarez, 129 F.3d 618 (D.C. Cir. 1997) (courts review agency action on the full administrative record)