Getting to First-in-Human Faster: What FDA’s New IND Pilot and NAMs Shift Mean for Sponsors

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For emerging biotechs, the race to first-in-human is often a race against the financing clock. Along with demanding scientific work, the path can also become fragmented: nonclinical studies, CMC readiness, regulatory strategy, protocol design, IRB review, site activation, and then the FDA’s IND review. Too often, those steps are planned sequentially when they need to be designed as one integrated program.

FDA’s new Expedited IND Pilot Program is an important attempt to address that problem. The agency has been direct about the competitive context: first-in-human trials can take up to two years to complete in the United States, while comparable early studies are often initiated more quickly in China and Australia. The question for sponsors is no longer simply, “what does FDA require?” It is, “how do we build an IND-enabling package that is scientifically credible, phase-appropriate, and ready to move without avoidable rework?”

The New FDA Pilot: More Collaboration, Not Lower Standards

The Expedited IND Pilot is not a new approval pathway, nor does it change FDA’s safety standard. It is a limited pilot designed for novel commercial first-in-human programs that will be conducted in the United States.

Under the model, a sponsor partners with a US-based Qualified Research Institution, or QRI, with expertise across nonclinical development, CMC, clinical development, regulatory affairs, and Phase 1 execution. FDA can then accept and review parts of the IND package on a rolling basis rather than waiting for every section to be complete.

That allows potential problems to be identified earlier. A gap in the toxicology strategy, a CMC issue, an unclear starting-dose rationale, or a clinical protocol concern may be resolved while the rest of the program continues to progress. FDA also encourages parallel planning for IRB review and site readiness, rather than waiting until the IND is fully assembled.

The important limitation is that the pilot is not designed for an unready program. Sponsors must already have sufficient preliminary nonclinical data for FDA to understand the development timeline and the likely path to an IND. The pilot is intended to make the path more coordinated and predictable, not to allow human dosing before the underlying evidence supports it.

Why Some Sponsors Start Development Outside the United States?

China’s appeal is often misunderstood. Sponsors do not go to China because they can bypass pharmacology, toxicology, or CMC. China’s drug-registration rules require all three before a clinical-trial application can proceed.

The difference is the overall development cycle. Once an application is accepted in China, the regulatory decision is generally expected within 60 days. If no notice is issued within that period, the application is deemed approved. China has also invested heavily in clinical research infrastructure, site networks, and faster study start-up.

For a resource-constrained biotech, the attraction is straightforward: generate an early human proof point more quickly, use that evidence to support partnering or financing, and then build the global development strategy. Several recent programs illustrate the model. Hengrui generated extensive clinical data in China for its dual GLP-1/GIP candidate before its US partner Kailera advanced the program globally. In oncology, AbbVie partnered with Simcere Zaiming on a trispecific antibody already in Phase 1 in both China and the United States, reflecting a more parallel global-development model.

FDA does not require that nonclinical studies be conducted in the United States. The sponsor must provide a robust pharmacology and toxicology package, generally supported by GLP-compliant pivotal studies, and identify where the work was conducted and where the underlying records can be inspected.

The policy objective behind the new pilot is therefore to preserve the scientific rigor of the US system while reducing the avoidable operational delays that cause early development, investment, and expertise to migrate elsewhere.

Where NAMs Fit

At the same time, FDA is changing how sponsors can build the nonclinical evidence base. New Approach Methodologies (NAMs), include human cell-based systems, organoids, organs-on-chips, computational models, and other approaches that may provide more human-relevant safety evidence than a traditional animal study.

FDA’s recent nonclinical-testing rule does not ban animal studies or impose a new requirement to use NAMs. It clarifies that animal studies are not the only acceptable route to establish safety before a medicine is tested in people. The evidentiary standard remains the same: the sponsor must provide enough reliable evidence to support the proposed clinical investigation.

This is particularly relevant for monoclonal antibodies, oncology biologics, and products for which there may be no pharmacologically relevant animal species. In those settings, a well-supported weight-of-evidence package may be more useful than a long, expensive animal study that does not answer the human safety question.

FDA has already identified circumstances in which it is open to streamlined nonclinical programs, including certain oncology biologics, CD3 bispecific antibodies, antibody-drug conjugates, and some cardiovascular or immunotoxicity questions. The agency’s inventory of streamlined nonclinical approaches is a useful starting point for sponsors.

The Transition Risk: NAMs Should Reduce Work, Not Add Another Workstream

NAMs are promising, but they do not eliminate the need for judgment. A sponsor cannot simply replace a conventional toxicology study with an organ chip or AI model because the technology is new. The method must be appropriate for the product, the risk, and the regulatory question.

For a complex small molecule, a novel modality, or a program with broad systemic, chronic, reproductive, or off-target risks, conventional in vivo evidence may still be necessary. The near-term risk is not that FDA’s NAM policy makes INDs harder. The risk is that sponsors attempt to use NAMs without a clear context of use, generate data that do not answer the relevant safety question, and then find themselves running conventional studies late in the program.

The practical approach is to use NAMs strategically:

• Define the first-in-human decision that must be supported.
• Identify which animal studies are genuinely necessary for that decision.
• Use human-relevant assays, modeling, and weight-of-evidence analyses where they reduce uncertainty or replace work that adds little value.
• Seek FDA input early enough that the nonclinical strategy is agreed before critical studies are underway.

EMA is taking a similarly measured approach. Its new voluntary NAM data-submission pilot allows companies, CROs, academic groups, and method developers to obtain non-binding feedback on NAM readiness outside a marketing application. That is a practical acknowledgement that the science is advancing quickly, but regulatory confidence must be built through real use cases.

What Sponsors Should Do Now

The opportunity is not to choose between traditional nonclinical development and NAMs. It is to build a phase-appropriate evidence strategy that uses the right tool for each question.

For sponsors preparing for first-in-human development, that means integrating nonclinical, CMC, clinical, regulatory, and operational planning early. The faster path is not the one with less science. It is the one where each study has a clear decision purpose, each workstream is sequenced intelligently, and potential regulatory concerns are identified before they become late-stage delays.

FDA’s Expedited IND Pilot and its NAM initiatives point in the same direction: development should be more collaborative, more human-relevant, and more efficient. For sponsors, the winning strategy will be to use that flexibility with discipline.