FDA Modernization Act authorizes single pivotal trial as case-by-case exception (21 USC 355(d))

President Bill Clinton signed the FDA Modernization Act (FDAMA) on November 21, 1997, the most significant FDA reform in decades. Section 115, codified at 21 USC 355(d), explicitly authorized FDA to accept data from a single adequate and well-controlled clinical investigation with confirmatory evidence when that single trial's results were sufficiently persuasive. This created a discretionary exception to the two-trial practice that had been FDA's interpretation since the 1962 Kefauver-Harris Amendments. The provision was designed for cases where a second trial would be unnecessary or impossible — such as rare diseases — while preserving FDA's authority to require two trials when warranted. The 2026 Makary-Prasad policy inverted this structure by making the single trial the default rather than the exception.