## Facts

- Federal authorities seized fifty boxes of Cafergot P‑B suppositories (CPB), a prescription drug marketed by Sandoz for about 35 years.
- CPB contained caffeine and ergotamine to treat vascular headaches and pentobarbital and bellafoline to address nausea associated with the headache ingredients.
- The government proceeded under the FDCA to treat CPB as an unapproved “new drug” lacking required proof of effectiveness.
- Sandoz argued CPB was not a “new drug” because it was generally recognized among experts as safe and effective (GRASE).
- Sandoz submitted, among other materials, expert affidavits from headache specialists describing a general medical consensus based on published reports and clinical experience, and noted that CPB’s anti-headache ingredients overlapped with an FDA-recognized product in tablet form.
- The district court granted summary judgment for the United States, concluding CPB was a “new drug” and that Sandoz lacked “substantial evidence” of effectiveness as required by the FDCA.

## Issues

1. Whether a manufacturer claiming a drug is GRASE (and therefore not a “new drug”) must meet the FDCA’s “substantial evidence” standard requiring adequate and well-controlled investigations.
2. Whether Sandoz’s summary judgment record created a genuine dispute that CPB’s effectiveness was supported by “substantial evidence” as defined by the FDCA and FDA regulations.

## Decision

- The First Circuit affirmed summary judgment for the United States.
- The court held that, for GRASE purposes, “substantial evidence” carries the specialized statutory meaning in 21 U.S.C. § 355(d): evidence from adequate and well-controlled investigations, typically including controlled clinical studies meeting regulatory criteria.
- The court concluded Sandoz’s showing—long marketing history, expert affidavits, published reports, and clinical experience—did not satisfy the statutory and regulatory requirements for adequate and well-controlled investigations.
- Because Sandoz produced no qualifying investigations, CPB was properly treated as a “new drug,” and seizure was authorized under the FDCA.

## Legal Principles

- Under the FDCA, a drug is a “new drug” unless it is generally recognized among qualified experts as safe and effective for its labeled uses (GRASE).
- The FDCA’s “substantial evidence” requirement is a term of art: it demands adequate and well-controlled investigations by qualified experts, not merely persuasive clinical experience or professional opinion.
- A claim of general recognition of effectiveness cannot be established without evidence meeting the same substantial-evidence standard used for new drug approval; GRASE does not provide a lesser evidentiary route.
- On summary judgment in an FDCA seizure action, the absence of any adequate and well-controlled investigations can eliminate any genuine issue of material fact as to effectiveness under the statutory standard.

## Conclusion

The First Circuit held that a manufacturer seeking to avoid “new drug” status through the GRASE exception must produce “substantial evidence” in the form of adequate and well-controlled investigations; because Sandoz did not provide such studies for CPB, the drug was properly treated as an unapproved new drug and the government’s seizure was upheld.


United States v. 50 Boxes More or Less, 909 F.2d 24 (1st Cir. 1990)