## Facts

- FDA approved lisdexamfetamine dimesylate (Vyvanse) in 2007 and granted five-year “new chemical entity” (NCE) marketing exclusivity under 21 U.S.C. § 355(j)(5)(F)(ii).
- Vyvanse is a prodrug that is converted in the body to dextroamphetamine, a previously approved active moiety.
- FDA regulations define NCE status by whether the drug contains an “active moiety” not previously approved; the regulation excludes esters, salts, and other noncovalent derivatives of previously approved active moieties.
- FDA interpreted its regulation to permit certain prodrugs (not merely esters, salts, or other noncovalent derivatives) to qualify for five-year exclusivity because the approved drug contains a distinct active moiety.
- In 2009, during Vyvanse’s five-year exclusivity period, Actavis submitted an ANDA for generic lisdexamfetamine referencing Vyvanse.
- FDA returned the ANDA as premature, concluding it could not be received during the five-year exclusivity period absent a statutory exception.
- Actavis sued under the APA, arguing Vyvanse was not an NCE because it yields a previously approved compound in vivo and therefore should not receive five-year exclusivity.

## Issues

1. Whether FDA permissibly interpreted the Hatch–Waxman exclusivity provisions and 21 C.F.R. § 314.108 to grant five-year NCE exclusivity to a prodrug that converts in vivo to a previously approved active moiety.
2. Whether FDA reasonably construed “active ingredient” and “active moiety” to focus on the approved drug molecule in the product, rather than the compound produced after ingestion.
3. Whether FDA’s decision to return Actavis’s ANDA as premature was arbitrary, capricious, or contrary to law under the APA.

## Decision

- The D.C. Circuit affirmed summary judgment for FDA and the brand manufacturer.
- The court upheld FDA’s interpretation of its own regulation as reasonable and not plainly erroneous or inconsistent with the regulation.
- The court agreed that FDA could treat lisdexamfetamine as a distinct active moiety for NCE purposes, despite metabolic conversion to dextroamphetamine.
- Because Vyvanse validly received five-year exclusivity, FDA lawfully returned Actavis’s ANDA as premature.
- The court rejected Actavis’s policy-based objections about possible “serial” exclusivity as speculative on the record presented.

## Legal Principles

- An agency’s interpretation of its own regulation is controlling unless it is plainly erroneous or inconsistent with the regulation.
- Under Hatch–Waxman and FDA’s implementing regulation, NCE exclusivity turns on whether the approved drug contains an active moiety not previously approved; the regulation expressly excludes esters, salts, and other noncovalent derivatives from NCE status.
- FDA may distinguish, based on chemistry and scientific judgment, between excluded noncovalent derivatives and prodrugs involving different molecular linkages when determining NCE eligibility.
- Under APA arbitrary-and-capricious review, courts will sustain FDA exclusivity determinations when grounded in the regulatory text and supported by a reasoned, science-based explanation.

## Conclusion

The court held that FDA reasonably interpreted its NCE regulation to grant five-year exclusivity to Vyvanse as a chemically distinct prodrug and, as a result, properly rejected Actavis’s ANDA as premature during the exclusivity period.


Actavis Elizabeth LLC v. Food & Drug Admin., 625 F.3d 760 (D.C. Cir. 2010)