Preclinical Formulations That Don’t Break Your IND and Keep Studies On Track

Preclinical Formulations That Don’t Break Your IND and Keep Studies On Track

You’ve got your lead molecule. You’re preparing for GLP toxicology. And your formulation scientist recommends a preclinical vehicle that “just works”—maybe a little DMSO, some Tween, a drop of acid or base. Problem solved, right?

Not so fast.

While it’s common (and sometimes necessary) to use enabling formulations during preclinical studies, choosing the wrong vehicle—or failing to document and justify it properly—can cause serious issues during your IND review.

At DavosPharma, we’ve helped dozens of biotechs bridge this gap the right way. Here’s what you need to know to avoid having your preclinical formulation break your IND.

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Why This Matters

Your GLP toxicology study is a cornerstone of your IND. It’s supposed to demonstrate that the test article—as close as possible to your clinical formulation—is safe for first-in-human dosing.

When preclinical and clinical formulations differ too much, regulators ask:
Are your tox data still valid? Or do we need more studies?

The wrong answer can mean delayed studies, bridging tox, or even a clinical hold.

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Common Mistakes We See

1. Using Formulations You Can’t Replicate in Humans

• Vehicles with high levels of DMSO or ethanol
• Use of surfactants (like Cremophor or polysorbates) that aren’t part of the intended clinical product
• pH extremes that irritate tissues or aren’t physiologically compatible

FDA red flag: “You dosed animals with one thing, but plan to dose humans with another.”

2. Skipping the Justification

You can use different vehicles in preclinical vs. clinical—if you justify why. But too many teams:

• Fail to explain why a solubilizer was chosen
• Don’t link impurity profiles across formulations
• Skip stability or compatibility testing in the tox vehicle

FDA red flag: “You haven’t shown the test article is representative or stable.”

3. Ignoring Route of Administration Alignment

It’s not just what you dose—it’s how. If your preclinical study uses IV and your clinical plan is oral (or vice versa), you’ll likely need a bridging study.

FDA red flag: “Exposure route and kinetics don’t match your clinical design.”

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Best Practices for IND-Friendly Preclinical Formulations

1. Design for Human Compatibility Upfront

Even if you need an enabling formulation, pick excipients that can potentially carry over into the clinic. If not, start planning your bridge strategy early.

2. Ensure Chemical & Physical Representativeness

Your test article should:

• Come from the same synthetic route
• Match impurity profiles and solid form
• Be formulated under well-documented, controlled conditions
  Even if it’s not GMP, it needs to be defensible.

3. Coordinate Across API, Formulation, and Tox Teams

The biggest mistakes happen when these functions work in silos. At DavosPharma, we build integrated CMC plans that ensure:

• Your preclinical formulation supports downstream development
• Your tox group knows what’s coming
• Your IND includes the data reviewers expect

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Real-World Example

One client approached us after their toxicology CRO rejected their preclinical test article—turns out, it had precipitated out of solution during dosing. Worse, their API team had changed solvents midstream and no one told the tox lab.

We helped them:

• Reformulate using a tolerable, clinic-compatible vehicle
• Re-test solubility, stability, and dose feasibility
• Prepare a bridging rationale and impurity comparability package for the IND

Result: The IND was accepted. The tox data held. And they avoided a costly repeat study.

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How DavosPharma Can Help

We act as your connective tissue between chemistry, formulation, and toxicology. Specifically, we:

• Design formulation strategies that support both tox and clinical
• Coordinate vendor timelines to align preclinical and CMC workstreams
• Review your IND to ensure the test article story is coherent, justified, and bulletproof

We’ve done it across small molecules, oncology candidates, steroids, and high-potency APIs—especially for first-time filers who can’t afford to miss.

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Final Word: Don’t Let “Good Enough” Formulations Undermine Great Science

Preclinical formulations that “get the job done” are fine—as long as they don’t derail your IND later.

Work with a partner who understands the nuance, the regulators, and the real-world pressures of early-stage development.

Need help planning your tox batch or formulation path?‍

Contact DavosPharma—we’ll help you design a program that works in animals and stands up to FDA review.