## Facts

- Astellas held the NDA for tacrolimus (Prograf), an immunosuppressant used to prevent organ rejection in transplant patients.
- Astellas characterized tacrolimus as a narrow therapeutic index/critical-dose drug and asserted that product switching could pose serious clinical risks.
- In 2007, Astellas filed a citizen petition asking FDA to require (i) enhanced bioequivalence testing (including studies in transplant patients and tighter limits) for generic tacrolimus and (ii) additional warning language about switching risks.
- On August 10, 2009, FDA denied the citizen petition and approved Sandoz’s ANDA for generic tacrolimus, finding it bioequivalent and approving labeling essentially matching the reference listed drug.
- Astellas sued under the Administrative Procedure Act (APA) to set aside the petition denial and ANDA approval as arbitrary and capricious.
- Astellas sought a temporary restraining order and preliminary injunction requiring FDA to withdraw approval of any generic tacrolimus pending judicial review; the opinion addressed only this request for interim relief.

## Issues

1. Whether Astellas showed a likelihood of success on the merits that FDA’s citizen-petition denial and ANDA approval were arbitrary and capricious under the APA.
2. Whether Astellas showed irreparable harm absent injunctive relief.
3. Whether the balance of harms favored an injunction withdrawing an already-approved generic product.
4. Whether an injunction would serve the public interest.

## Decision

- The court denied the motion for a temporary restraining order and preliminary injunction.
- Astellas failed to show a likelihood of success because FDA’s bioequivalence determinations and related scientific judgments were entitled to substantial deference and were supported by the administrative record.
- The court accepted FDA’s position that ANDA labeling generally must be essentially the same as the reference listed drug, making Astellas’s requested generic-specific warnings inconsistent with the ANDA framework.
- Astellas did not show irreparable harm; alleged patient risks were largely predictive rather than concrete and imminent, and expected economic losses from generic entry were not enough on this record.
- The balance of harms and public interest weighed against withdrawing approval after generic marketing had begun, given Congress’s generic-drug scheme and the interest in access to lower-cost, FDA-approved medicines.

## Legal Principles

- Under APA review, a court upholds agency action if it reflects consideration of relevant factors and no clear error of judgment; courts do not substitute their judgment for an expert agency’s scientific determinations.
- Requests for preliminary injunctive relief require showing: (i) likelihood of success on the merits, (ii) irreparable harm, (iii) balance of equities favoring relief, and (iv) consistency with the public interest.
- FDA receives substantial deference on technical matters such as bioequivalence methodology and evaluation of scientific evidence supporting generic approval.
- The ANDA scheme generally requires generic labeling to be essentially the same as the reference listed drug; generic-specific warning language may be rejected as inconsistent with that statutory structure.
- Economic harm and loss of market share from generic competition, without more, typically do not establish irreparable injury sufficient to justify extraordinary interim relief.

## Conclusion

The court refused to halt FDA’s approval of generic tacrolimus because Astellas did not meet the demanding preliminary-injunction standard, particularly given deference to FDA’s scientific judgments, the statutory constraints on generic labeling, and the public interest in maintaining access to FDA-approved generics.


Astellas Pharma US, Inc. v. Food & Drug Admin., 642 F. Supp. 2d 10 (D.D.C. 2009)