Building on the foundational principles of ATMP specification setting discussed in Part 1, this second session will focus on advanced and emerging challenges that arise in rare disease, personalized, and accelerated development programs. These scenarios increasingly define the cell and gene therapy landscape and require specification strategies that balance scientific rigor, operational feasibility, and regulatory expectations under significant program and process uncertainty.

The session will begin by addressing specification settings for rare and ultra-rare programs, where the first GMP-manufactured lot may serve as both first-in-human and pivotal material. Speakers will discuss how phase-appropriate specifications can be established when product knowledge and material availability is minimal, while still enabling late-stage control and characterization expectations. Approaches for prospective planning, data generation, and risk management will be explored to support this dual-use reality.

Next, the session will examine the unique challenges of personalized therapies, where each manufactured batch corresponds to a single patient. Discussion will focus on how companies define, justify, and evolve specifications based not only on QTPP and clinical data, but also on manufacturing and process capability. Strategies for interpreting and aggregating data in an “n=1” paradigm will be shared, along with practical models for collaboration between CMC and clinical teams to contextualize product quality against patient outcomes.

Finally, the session will explore specification challenges in accelerated development pathways. Case-based discussions will consider early-phase programs with strong expectations of efficacy, as well as programs entering Phase 2/3 with compelling clinical data. Topics will include identifying critical quality data needed to support late-stage development and approval, opportunities for post-approval learning, and managing the risk of overly tight commercial specifications driven by limited batch numbers or small patient populations during clinical development.

Session Speakers:

Kedar Dave, Bristol-Myers Squibb Company

Between Scylla and Charybdis: Navigating Specification Setting for Rare and Ultra Rare Disease Programs

Joshua Kidder, Ultragenyx Pharmaceutical Inc

Shilpa Suravajhala, Vertex Pharmaceuticals Incorporated

Additional Panelist:

John Schiel, Advanced Research Projects Agency for Health (ARPA-H)

Ilya Shestopalov

Appearances