## Facts

- SmithKline Corporation marketed Dexamyl, a combination of dextroamphetamine sulfate and amobarbital, for obesity since 1950.
- After the 1962 FDCA amendments required “substantial evidence” of effectiveness, SmithKline filed NDAs for Dexamyl in 1971 and submitted five double-blind, multi-investigator clinical trials in 1973.
- The FDA concluded the submissions did not provide “substantial evidence” because the trials were not “adequate and well-controlled investigations” under the statute and FDA regulations.
- The FDA’s objections included subject selection (e.g., anxious subjects), adequacy of washout periods, consistency of observation, data pooling, use of active controls instead of placebo, and risks of observer or analyst bias.
- SmithKline submitted expert affidavits supporting the studies’ adequacy and sought an evidentiary hearing to contest the FDA’s methodological criticisms.
- The FDA refused to grant a hearing and denied approval of the pending NDAs; SmithKline petitioned for review.

## Issues

1. Whether Dexamyl was exempt from the 1962 effectiveness amendments under the statutory grandfather clause.
2. Whether the FDA could deny an evidentiary hearing and dispose of the NDAs through summary procedures when the adequacy of submitted clinical studies depended on disputed scientific and methodological judgments.

## Decision

- The court held Dexamyl was not grandfathered and remained subject to the 1962 “substantial evidence” effectiveness requirement.
- The court vacated the FDA order to the extent it denied a hearing and remanded for further proceedings.
- The court held the FDA improperly used summary procedures because SmithKline’s submissions and supporting affidavits created genuine issues of material fact about the adequacy and probative value of the clinical investigations.

## Legal Principles

- The 1962 effectiveness amendments and their narrow grandfather clause do not exempt drugs covered by effective NDAs as of the statutory cutoff date, particularly where the product’s labeling/indications have materially changed.
- “Substantial evidence” under the FDCA requires evidence from “adequate and well-controlled investigations” by qualified experts, as elaborated by FDA regulations.
- The FDA may use summary judgment–like procedures to deny an NDA hearing only when the applicant has clearly failed to submit evidence capable of meeting the “substantial evidence” standard, such that no material factual disputes exist.
- When the agency’s rejection of studies rests on contestable scientific, statistical, or methodological judgments and the applicant offers facially substantial data and expert support, the applicant must receive an opportunity for an evidentiary hearing (or comparable fact-finding) before disapproval.

## Conclusion

The court rejected the claim that Dexamyl was exempt from the 1962 efficacy requirements, but it limited the FDA’s ability to dispose of NDAs without a hearing where the agency’s criticisms of clinical trials depend on disputed scientific judgments raised by the applicant’s evidence.


SmithKline Corp. v. Food & Drug Admin., 587 F.2d 1107 (D.C. Cir. 1978)