## Facts

- Ubiotica Corporation developed a multi-ingredient drug regimen known as the “U Series Drugs,” consisting of roughly fifty ingredients and proposed for treatment of mongolism (Down syndrome).
- After the 1962 amendments to the Federal Food, Drug, and Cosmetic Act (FDCA) added an effectiveness requirement for new drugs, Ubiotica sought federal approval to market the regimen.
- Ubiotica submitted a New Drug Application (NDA) under 21 U.S.C. § 355 and also filed a notice claiming an investigational exemption under § 355(i).
- In November 1963, FDA notified Ubiotica that the investigational exemption was terminated because conditions for the exemption had not been met.
- Ubiotica and Dr. Henry Turkel previously attempted to obtain judicial review of the termination of the investigational exemption; the Sixth Circuit held in Turkel v. FDA that such action was not reviewable under § 355(h) except in connection with review of a later order refusing to approve an NDA.
- FDA proceeded to evaluate the NDA under the statutory requirements of § 355(b) (contents of an NDA) and § 355(d) (grounds for refusing approval), focusing on whether the application showed the drug was safe and effective for its intended use.
- Ubiotica requested and received an administrative hearing before an FDA hearing examiner after the agency proposed refusing approval.
- The agency record included scientific and medical objections that Ubiotica’s submissions did not include adequate, well-controlled clinical investigations and did not provide sufficient reliable data to establish safety and effectiveness for the claimed indication.
- The Commissioner ultimately issued an order refusing to approve the NDA, concluding that the application did not meet FDCA requirements.
- Ubiotica petitioned the United States Court of Appeals for the Sixth Circuit for review under 21 U.S.C. § 355(h), arguing that the denial lacked support in the record and that the administrative hearing was unfair due to limits on witnesses, cross-examination, and access to certain documents.

## Issues

1. Whether the Commissioner lawfully refused to approve Ubiotica’s NDA under 21 U.S.C. § 355(d) because the record lacked substantial evidence that the drug was safe and effective for its intended use.
2. Whether Ubiotica was denied a fair administrative hearing based on the hearing examiner’s rulings concerning witnesses, cross-examination, and production of documents.
3. Whether, and to what extent, the termination of Ubiotica’s investigational exemption could be reviewed in a petition challenging the later NDA refusal order.

## Decision

- The Sixth Circuit denied Ubiotica’s petition for review and affirmed the Commissioner’s order refusing to approve the NDA.
- The court held that the Commissioner’s findings were supported by substantial evidence on the record as a whole, including the determination that Ubiotica failed to provide adequate, well-controlled clinical data demonstrating effectiveness and sufficient information to show safety for the proposed use.
- The court rejected Ubiotica’s claim of an unfair hearing, finding no reversible error in the hearing examiner’s management of evidence, witnesses, and document requests and no showing of prejudice that would warrant setting aside the agency’s decision.
- Consistent with Turkel, the court treated challenges related to the investigational exemption as reviewable only in connection with the NDA-refusal review, but it found nothing that justified overturning the refusal order.

## Legal Principles

- The FDCA prohibits introducing a “new drug” into interstate commerce unless an NDA has been submitted to and approved by FDA. 21 U.S.C. § 355.
- Section 355(b) specifies information that must be included in an NDA; Section 355(d) lists permissible grounds for refusing approval, including lack of required data and lack of substantial evidence that the drug will have the claimed effect under labeled conditions of use.
- Under the 1962 amendments, the sponsor must show effectiveness as well as safety; “substantial evidence” of effectiveness generally requires evidence from adequate and well-controlled investigations by qualified investigators, not uncontrolled observations or unsupported clinical impressions.
- On judicial review under § 355(h), the court does not decide scientific questions anew; it asks whether the Commissioner’s findings are supported by substantial evidence on the record as a whole and whether the decision is within statutory bounds.
- Administrative hearing officials may control the scope of evidence and procedural matters in NDA proceedings, and limits on requested witnesses or documents do not establish an unfair hearing absent a showing that the rulings deprived the applicant of a meaningful opportunity to present its case and caused prejudice.
- Termination of an investigational exemption is not independently reviewable under § 355(h); review may occur only in the context of a petition challenging a later order refusing to approve the NDA.

## Conclusion

Ubiotica Corp. v. Food and Drug Administration holds that FDA may refuse to approve a new drug application when the sponsor fails to provide substantial evidence—typically from adequate and well-controlled clinical investigations—showing the drug is safe and effective for its intended use, and that such a refusal will be upheld on review when supported by substantial evidence and reached through an administrative hearing that, even with reasonable procedural limits, affords the applicant a fair opportunity to present and test the evidence.


Ubiotica Corp. v. Food and Drug Administration, 427 F.2d 376 (1970)