This article by Facet’s own Tom Hallam, Ph.D., MBA, first appeared in the Innovation Insights section of Life Sciences Review.
Nearly half of New Drug Application (NDA) or Biologics License Application (BLA) submissions have historically failed to win first-cycle approval, and the deficiencies that sink them are traceable. Two decades of FDA data point to a single milestone most companies treat as a formality: the pre-NDA or pre-BLA meeting.
In 2006, the U.S. Food & Drug Administration (FDA) commissioned an independent review of every New Molecular Entity (NME) application that had reached a first action over the prior three years. A decade later, an assessment of the enhanced communication program under PDUFA V (FDA’s fifth authorization of the Prescription Drug User Fee Act) found the same deficiency patterns still driving first-cycle failures. Companies are still walking into the pre-NDA/BLA meeting with the same blind spots FDA flagged in 2006.
Timing, Not Science, Decides the Outcome
Across seventy-seven applications, deficiencies split almost evenly across safety, efficacy, and chemistry, manufacturing, and controls (CMC). Missed endpoints were the single biggest driver, ahead of trial design and execution problems. But what mattered more than the deficiency was when it surfaced. Among multi-cycle applications that had held an End-of-Phase-2 meeting:
- 25% had the critical issue identified at that meeting
- 36% had it identified at the pre-NDA or pre-BLA meeting
- 41% weren’t identified until the review itself, after the clock had started, which is too late to resolve in time for a first-cycle approval
FDA’s own interviews pointed to why: the pre-NDA/BLA meeting was generally regarded as administrative. In practice, meetings focused on application format rather than a substantive review of the data. Applicants who held one still saw only a 47% first-cycle approval rate (essentially a coin flip), while those who skipped it fared worse at 33%.
Imagine you’re about to open a $500 million building. The city offers a pre-inspection: a walkthrough with the same inspectors who’ll decide whether you can open your building. But instead of pressure-testing the building’s systems and construction plans, you spend the meeting discussing the color of the application cover. Then you can’t act surprised when the building fails inspection and the project stalls.
Structured Dialogue Correlates With First-Cycle Approval
A decade after the 2006 report, FDA revisited the question, this time with a wider cohort and direct sponsor interviews. It evaluated the enhanced communication program under PDUFA V, which applies to NME NDAs and original BLAs received from October 2012 through September 2017. Its evaluation, covering applications acted on through June 2016, found first-cycle approval rates jumping to 79.5%, up from 54.8% in the PDUFA IV baseline.
Applicants interviewed for the assessment were consistent. They didn’t credit a single meeting, but a full arc of structured, substantive dialogue running from early development through mid-cycle and late-cycle checkpoints.
Meeting Preparation Is the Actual Differentiator
The distinction is not the meeting itself. It’s the quality of the conversation, which hinges on the preparation. A pre-NDA or pre-BLA meeting is best used to challenge the application’s vulnerabilities before they jeopardize approval. When companies walk in with weak points named, likely objections in mind, and a plan for what happens if the data does not hold, it becomes the single highest-leverage exchange in the entire submission process. It also sets the tone for every FDA interaction that follows.
That’s especially true for novel therapeutics demonstrating feasibility with limited precedent. When there’s no established regulatory pathway to reference, the pre-NDA/BLA meeting is the only chance to align with FDA reviewers on what evidence will actually satisfy them before the data package is locked and submitted.
That’s why a regulatory strategy partner with not just experience across a wide range of therapeutic areas, but a deep understanding of division-specific reviewer behavior from both sides of the table can be a differentiator. Sponsor teams with finite regulatory expertise have trusted Facet Life Sciences to maximize pre-NDA/BLA meetings for almost fifteen years.
Facet’s scientific and product development experts know which questions each review team tends to ask before the meeting is ever scheduled, so the briefing books we build answer those questions preemptively instead of reactively. Our subject-matter experts seek to understand each program’s exact science, tell the story of the product in the best light, and pressure-test the NDA package with FDA reviewers.
Before the Clock Starts
Across twenty years of FDA data, it’s clear that the pre-NDA/BLA meeting step is critical to timely approval. For a company heading into a pre-NDA or pre-BLA meeting in the next twelve to eighteen months, the question is not whether the meeting matters. It is whether the briefing book the company enters the room with reflects a genuine stress test of the application data, or a review of the table of contents.
References
Booz Allen Hamilton. Independent Evaluation of FDA’s First Cycle Review Performance – Retrospective Analysis Final Report. Prescription Drug User Fee Act III – Initiatives & Evaluations. 2006.
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