## Facts

- Serono Laboratories manufactured Pergonal, an FDA-approved menotropins fertility drug containing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) derived from human urine.
- An ANDA was submitted for Repronex as a generic version of Pergonal under the Hatch-Waxman framework, later pursued by Ferring Pharmaceuticals.
- Serono filed a citizen petition urging the FDA to withhold ANDA approval, asserting (1) Repronex’s FSH was not “the same as” Pergonal’s due to differences in FSH isoforms tied to carbohydrate side chains, and (2) differences in inactive ingredients created safety or approvability problems.
- The FDA denied the petition and approved Repronex, concluding that exact isoform matching for a heterogeneous protein product is not feasible, the observed isoform differences were not clinically significant, and inactive-ingredient differences (including lactose concentration and uncharacterized urinary proteins (UUPs)) did not present safety concerns.
- Serono sued seeking to block or rescind approval; the district court granted a preliminary injunction barring FDA approval/maintenance of approval.
- The FDA and Ferring appealed; the court of appeals stayed the injunction and reviewed whether preliminary injunctive relief was proper.

## Issues

1. Whether Serono showed a likelihood of success in proving the FDA acted unlawfully or unreasonably in finding Repronex’s FSH was the “same as” Pergonal’s active ingredient for ANDA purposes.
2. Whether Serono showed a likelihood of success in proving the FDA acted unlawfully or unreasonably in concluding inactive-ingredient differences (including lactose and UUPs) did not render Repronex unsafe or otherwise unapprovable.
3. Whether, under the preliminary-injunction standard and APA review, the district court properly enjoined FDA approval of the ANDA.

## Decision

- The court of appeals vacated the preliminary injunction.
- Serono failed to satisfy preliminary-injunction requirements, especially likelihood of success on the merits.
- The FDA’s scientific judgments and its interpretation of “same as” for a heterogeneous protein product were reasonable and entitled to deference.
- The FDA reasonably applied the regulatory standards in effect when the ANDA was submitted rather than later-adopted requirements.
- The FDA’s safety assessment regarding lactose and UUPs was supported by evidence and not shown to be arbitrary or capricious.
- The public interest in access to lower-cost generics weighed against injunctive relief absent a strong showing of likely illegality or unresolved safety risk.

## Legal Principles

- Under APA review, courts defer to an agency’s reasonable scientific and technical judgments within its statutory authority.
- For complex, heterogeneous biologic products, “same as” in the ANDA context need not require identical isoform patterns if the agency reasonably concludes clinically relevant characteristics are comparable and batch-to-batch variation is similar.
- An agency may reasonably evaluate an application under regulations and policies in effect at the time of submission and decline to apply later standards retroactively absent a clear directive.
- A preliminary injunction blocking or undoing FDA drug approval requires a strong showing of likely success on the merits; disagreement with agency science, without showing arbitrariness or legal error, is insufficient.

## Conclusion

The D.C. Circuit set aside the injunction because Serono did not show it was likely to prove the FDA’s approval decision unlawful under deferential APA review, and the balance of equities and public interest did not justify blocking market entry of the generic drug.


Serono Labs., Inc. v. Shalala, 158 F.3d 1313 (D.C. Cir. 1998)