## Facts

- E.R. Squibb & Sons, Inc. manufactured four oral combination drugs sold as “Mysteclin,” each combining tetracycline with an antifungal (nystatin or amphotericin B).
- The combination was justified on the theory that tetracycline therapy could lead to *Candida albicans* overgrowth that antifungals would prevent.
- After the 1962 amendments to the Federal Food, Drug, and Cosmetic Act (FDCA) imposed an efficacy requirement, the FDA reviewed drugs approved under the earlier safety-only regime.
- Acting under 21 U.S.C. § 355(e), the Commissioner of Food and Drugs issued an order withdrawing approval and revoking certification for the Mysteclin products for lack of “substantial evidence” of effectiveness.
- Squibb petitioned the D.C. Circuit for direct review of the FDA’s final withdrawal and revocation order.

## Issues

1. Whether Squibb produced “substantial evidence” that Mysteclin was effective for its labeled uses under the post-1962 FDCA standard.
2. Whether the FDA applied an impermissibly stringent approach to evaluating Squibb’s clinical and scientific evidence as “adequate and well-controlled investigations.”
3. Whether the withdrawal and revocation order was arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law under the Administrative Procedure Act (APA).

## Decision

- The court denied the petition for review and upheld the FDA’s withdrawal of approval and revocation of certification for the four Mysteclin products.
- The court held that the FDA reasonably found Squibb’s submissions did not constitute “substantial evidence” of effectiveness as defined by the FDCA.
- The court concluded that the FDA’s decisionmaking was reasoned and therefore not arbitrary or capricious under the APA.

## Legal Principles

- The FDCA’s post-1962 efficacy requirement applies to drugs approved before 1962; the FDA may withdraw prior approvals upon finding a lack of “substantial evidence” of effectiveness based on new information evaluated with the original record. (21 U.S.C. § 355(e))
- The manufacturer bears the burden to come forward with “substantial evidence” of effectiveness, meaning evidence from “adequate and well-controlled investigations” that would allow qualified experts fairly and responsibly to conclude the drug achieves its claimed effect. (21 U.S.C. § 355(d))
- In reviewing FDA withdrawal decisions, courts apply APA arbitrary-and-capricious review and generally defer to the FDA on scientific and methodological judgments when the agency explains its reasoning and ties its conclusions to the statutory standard.
- For combination drugs, evidence must support the claimed therapeutic contribution of the added component(s); failure to show a clinically meaningful incremental benefit can justify withdrawal for lack of substantial evidence.

## Conclusion

The D.C. Circuit upheld the FDA’s withdrawal of approval for Squibb’s pre-1962 combination drugs because Squibb failed to provide adequate, well-controlled evidence that adding antifungals to tetracycline produced the claimed clinical benefit, and the FDA’s scientific assessment and explanation satisfied APA review.


E.R. Squibb & Sons, Inc. v. Bowen, 870 F.2d 678 (D.C. Cir. 1989)