More than 90% of drug candidates never make it to market. Many potential treatments fail not because the science is flawed but due to poor strategic planning. Even if the drug is ultimately approved, delays such as being placed on clinical hold after Investigational New Drug (IND) submission or filing protocol amendments can create significant financial and time burdens.
For early-stage biotechs, it’s easy to focus on getting compelling preclinical data as quickly as possible. But without a clear plan that aligns preclinical decisions with clinical and regulatory expectations, costly missteps can occur. Inappropriate species selection, poorly designed toxicology studies or PK/PD evaluations, and a lack of validated biochemical assays can all lead to program delays and failures.
The good news? Many of these pitfalls are avoidable. With early guidance from experienced advisors and a strategic development plan built with the end in mind, emerging biotechs can substantially de-risk their programs, optimize the use of resources and move forward into the clinical stages with greater confidence.
This article explores four of the most common pitfalls in preclinical development—and how early, strategic planning can help you avoid them.
Preclinical development: Your gateway to IND approval
Preclinical development serves as the foundation for a successful IND submission. During this stage, drug candidates are evaluated in a series of nonclinical studies to assess their safety, pharmacokinetics (PK), pharmacodynamics (PD) and biological activity. The resulting data guide first-in-human dose selection and study design, while also providing regulatory authorities with the evidence required to approve the initiation of clinical trials.
Mistakes in preclinical planning—such as poor study design, inappropriate model selection, or inadequate analytical method development—can result in clinical holds, the need to repeat studies, or expensive protocol amendments down the line. To help you avoid these setbacks, we’ve outlined four of the most common pitfalls in preclinical development.
Pitfall #1: Incorrect species selection
Selecting the right animal species for toxicology studies is a critical decision that can make or break the relevance of your preclinical data. If the species chosen doesn’t adequately mirror human biology—or if there’s insufficient data to support the selection—regulators may question the validity of your findings. This risk is even greater for biologics, where species differences in target binding, immune response, or metabolism can significantly impact the interpretation of safety data.
To avoid this pitfall, species selection must be grounded in both mechanistic understanding and regulatory precedent. That means generating early pharmacological data to confirm target engagement, conducting in vitro binding studies across species and consulting existing literature or regulatory guidance where available.
Pitfall #2: Inadequate exposure in toxicology studies
One of the most common issues in preclinical development is designing toxicology studies that fail to achieve appropriate systemic exposure. These studies are intended to assess the safety of a drug candidate, but if the formulation is poorly absorbed or the dosing isn’t optimized, the results may not reflect the true risk profile.
For instance, a formulation that limits bioavailability might never reach the levels needed to trigger potential toxic effects, leading to an incomplete or misleading safety assessment. On the other hand, selecting an excessively high dose—such as an arbitrary 10X margin—without scientific justification can raise red flags with regulators and compromise the study’s relevance.
To avoid this pitfall, exposure levels must be carefully matched to the intended clinical context. That means selecting a formulation and dose range that support your Target Product Profile (TPP) and allow for meaningful interpretation of toxicology data. Early consultation with pharmacologists and regulatory experts can help ensure that your studies generate the right data.
Pitfall #3: Poor assay development and validation
Assays used in preclinical studies must be fit for purpose—meaning their development and validation should align with the phase of development and the intended use of the data. While GLP-compliant assays are required for regulatory toxicology studies, early exploratory studies may not demand full validation. However, skipping early performance assessments can jeopardize data quality and lead to delays when assays fail under real-world conditions.
To avoid setbacks, assay suitability should be evaluated early, particularly for the biological matrix and sample types being used. Collaborating with an experienced CRO during method development can help optimize assay performance and ensure compatibility with small sample volumes—this is especially important when working with smaller species. If samples will be frozen for future analysis, analyte stability should be confirmed under relevant storage and handling conditions, keeping in mind that stability in biological matrices may differ from spiked controls.
Pitfall #4: Misaligned PK/PD studies
Pharmacokinetics and pharmacodynamics (PK/PD) are central to understanding how a drug behaves in the body, and getting them wrong can derail an otherwise promising program. If bioavailability is too low due to poor absorption or rapid clearance, clinical efficacy may be compromised. Similarly, suboptimal dosing in animal studies may not translate to meaningful clinical outcomes.
To avoid this, PK/PD study design—including route of administration, formulation, and dosing—must be aligned with the intended clinical use. Significant changes later on can trigger costly repeat studies or bridging experiments. A well-structured development plan, supported by experienced partners, helps ensure your studies are not only scientifically sound but also IND-ready and lays the groundwork for a smooth transition to clinical trials.
Strategic planning and partnership: An informed path forward
Bringing a new therapy to market requires a cohesive strategy that connects preclinical decisions with clinical and regulatory goals. Without early alignment, even promising programs risk delays, added costs or clinical holds. That’s why strategic planning is essential to help you avoid common missteps and move forward with greater clarity and confidence.
The right team of advisors and CDMO and CRO partners can provide critical insights into potential failure points, helping you navigate common challenges encountered on the drug development journey, from study design and assay development to regulatory reporting.
KreaMedica supports emerging biotechs with tailored scientific program management and functional outsourcing solutions. Through our global network of experts, we offer:
- Hands-on project management and monitoring
- Access to external experts in regulatory, clinical, and CMC development
- Strategic outsourcing for non-clinical and clinical programs
Let us help you build a smarter development plan—one that avoids costly missteps, optimizes the use of resources and keeps your program on track for success.