I am loving what I am hearing at FDA, and I am loving what I am seeing.
The Rare Disease Framework Initiative. The proposed CDER/CBER Rare Disease Evidence Principles (RDEP) process. The Expedited Investigational New Drug (IND) Pilot Program, advancing HHS's Operation TrialBlazer initiative. And the newly issued draft guidance, Individualized Human Genome Editing Products: Considerations for BLA Submission and Post-Approval Management.
These are meaningful developments for a community that has spent years explaining why conventional approaches can be difficult, and sometimes impossible, to apply to rare and ultra-rare diseases.
What excites me just as much is the responsibility these efforts ask industry to take.
My takeaway from recent conferences, including MESA 2026 and the NORD Summit, is that productive engagement asks us to do our part. Our COO/CRO at RareMoon Consulting has been adamant about this for years.
Effective development requires active partnership. Sponsors and their regulatory advisors need to bring well-developed plans, clearly articulated scientific and regulatory rationales, and practical proposed solutions to difficult questions.
So, what does that look like?
What does "come early, come often" actually mean?
It means coming as early as you can with enough substance to make the interaction useful, then continuing to engage as your program needs it.
Regulatory professionals have historically been trained around a familiar sequence: INTERACT, pre-IND, end-of-Phase 1, end-of-Phase 2. These interactions offer important opportunities to discuss readiness for clinical development and plans for the next stage, including the studies intended to support a marketing application.
In reality, rare disease and advanced therapy programs do not necessarily develop in that sequence. Scientific questions, manufacturing challenges, and consequential decisions arise between those milestones. Think of the advances, challenges, data outputs, changes in direction, manufacturing issues, and endpoint developments, or the new data that challenge benefit/risk and timing of administration. Your engagement strategy needs to respond to the program as it develops, with milestone meetings fitting around it.
Too often, we see sponsors rush toward a milestone meeting before their proposals are developed, either to get answers to one or two questions and broad feedback on the rest, or to meet investor commitments. Others save so many unresolved issues for one meeting that focused questions become broad requests for feedback. The opportunity to obtain specific, actionable advice gets lost to an overloaded agenda.
We also see the opposite: sponsors wait until the next scheduled milestone to raise an issue that needed discussion months earlier. By then, they may be explaining a decision already made, or a study already completed, with fewer practical options for addressing FDA's concerns.
"Come early, come often" in this space asks us to think differently. Come at the right time, prepared.
What needs discussion now? Could a focused interaction help resolve a specific issue between broader milestone meetings? Has earlier feedback raised a question that deserves further engagement before we proceed? Are we waiting because the program needs more work, or because the next meeting on our development timeline is still six months away?
Use milestone meetings for the substantive discussions they are designed to support. Build additional, fit-for-purpose interactions around the questions and decisions that arise along the way. Work with the review team to identify an appropriate way to have those conversations, with a clear purpose and enough context for meaningful feedback.
Prepared means ready for a substantive discussion: a candid conversation about uncertainty, a proposed approach, and what you need FDA's input to resolve.
And "often" matters. Engagement belongs throughout development, revisiting assumptions, working through challenges, and seeking feedback while it can still shape the path forward. The program needs to set the pace.
When should I meet with the FDA? Which meeting type should I request?
At RMC, we start a step earlier.
What are we facing? What is uncertain? Where do we need feedback or alignment? What is stopping this program from reaching its next milestone?
Those answers help determine the timing, scope, and appropriate mechanism for engagement. A meeting type is a tool within the strategy, and choosing it starts with understanding the problem we need to solve.
One point from CDRH Director Michelle Tarver's remarks at NORD stayed with me, on the relationship between the specificity of a question and the usefulness of the answer: "ask an amorphous question, and you'll get an amorphous answer."
What should we bring to the discussion?
A proposed path forward, with every element justified.
Explain what you recommend and why. Identify the limitations of the evidence. Address the risks. Describe the alternatives you considered and the consequences of choosing among them.
If a conventional approach is not feasible, explain the specific constraint and propose an alternative that can answer the underlying scientific question.
Small populations and limited precedents make this work harder, and they make a clear rationale more important.
Where do patients fit?
At the beginning, and throughout development.
In rare indications, there may be little precedent to help sponsors and regulators determine what constitutes a clinically meaningful outcome. Understanding what patients experience, what functions they most want to preserve, and what burdens they can reasonably accept is essential to building a relevant development strategy, especially in advanced therapies, where we are often talking about one, very risky dose.
FDA's Rare Disease Framework Initiative explicitly includes earlier patient input and patient perspectives at defined development milestones. That should shape how we develop our plans before bringing them to the FDA.
Which pathway or pilot is right for my program?
That depends on the program's scientific questions, development stage, evidence, and eligibility.
These opportunities serve different purposes. RDEP is a proposed process for certain genetically defined diseases with very small populations. The Expedited IND Pilot focuses on development leading to first-in-human studies. The new individualized genome-editing draft guidance addresses BLA submission and post-approval management for products with multiple patient-specific variants.
A program's strategy may draw on more than one mechanism over time, and a pilot is one tool within a complete regulatory strategy.
This is why I am enthusiastic about the Qualified Research Institution, or QRI, model within the Expedited IND Pilot. FDA describes the QRI as an accountable scientific partner that helps sponsors prepare stronger submissions and identify issues before components reach the Agency.
That expectation resonates with how we believe regulatory advisors should work: thoughtfully, transparently, respectfully, and with scientific and regulatory rigor.
What does industry need to do now?
Reassess the assumptions driving our development plans.
Traditional end-of-Phase 1 and end-of-Phase 2 touchpoints remain useful, and they may not map neatly onto a rare disease gene therapy program. We need to identify when consequential decisions arise and plan appropriate engagement around them.
We also need to bring constructive ideas forward when an evidentiary approach could be more practical, a process could work better, or a development strategy could better reflect the disease and its patients while preserving FDA's standards.
In this industry, in this climate, time is currency. Regulatory expertise should help teams identify the decisions that matter and seek feedback while there is still time to act on them.
Patients, sponsors, and regulators share a fundamental objective: reaching sound conclusions about safety and effectiveness as efficiently and rigorously as the evidence allows.
I am encouraged by the FDA's willingness to reconsider how we get there.
Now we need to meet that effort with preparation, practical solutions, and a willingness to work through the difficult questions together.