How Past FDA Reviews Can Guide Better Preclinical Study Design
Designing effective preclinical in vivo studies requires more than a thorough understanding of published scientific literature. Insights from regulatory agencies can help researchers anticipate potential obstacles, strengthen their evidence packages, and improve the likelihood of clinical progression. As regulatory expectations continue to evolve, accessing these insights early is becoming increasingly valuable. This blog will explore how publicly available FDA resources can inform study design and support more efficient drug development.
Preclinical Design Needs More Than the Literature
When designing preclinical in vivo studies, many researchers aim to gain as comprehensive an understanding of the relevant literature as possible. While this is certainly a solid strategy for selecting appropriate models and experimental parameters, it doesn’t account for other types of information that can improve their chances of progressing past the IND stage. Ultimately, preclinical evidence generated by a study will be scrutinized by regulators who have in-depth knowledge of the therapeutic area, including the strategies commonly used within it. As such, they may already have established opinions of what models are appropriate for testing a given hypothesis. This means researchers may be at a disadvantage if their approach has previously been deemed insufficient in a specific context, regardless of how well designed it is.
A systematic analysis of INDs placed on hold revealed that sponsors with less regulatory experience had more stalled INDs compared to other sponsors1. This suggests that familiarity with regulatory expectations may help to reduce the risk of avoidable delays. What some researchers may not be aware of is that FDA guidance for preclinical study design is often freely available and can help increase the chances that their study designs meet regulatory expectations from the start.
Where to Find FDA Guidance for Preclinical Study Design
The FDA publishes a range of documents that can help research teams anticipate regulatory obstacles and improve their chances of success. For many approved drugs, these include the product's regulatory history and FDA staff reviews of its safety and effectiveness. They also include pharmacology and nonclinical reviews, which show how reviewers evaluated a drug and may point to experiments that researchers could otherwise overlook. In this way, researchers can gain context on the relevance of a model or a particular experimental setup to the hypothesis they are testing. Such information can accelerate product development.
The Benefits of Accessing Regulatory Reviews Early
Many researchers are unsure what regulators expect yet, in many cases, the answers are already publicly available and can offer immense benefits.
Lower Downstream Costs
Drug development is costly. Redesigning a program or repeating pivotal experiments in response to reviewer feedback can carry significant financial consequences, and smaller or less established companies may be unable to continue. Understanding regulatory expectations in advance reduces the risk of avoidable setbacks and improves the chances of success.
Greater Reviewer Confidence
Addressing details that others have overlooked shows agencies that you understand the therapeutic landscape and have expertise in the area. Clear justification of biological relevance, dose rationale, and controls also makes it easier for reviewers to understand and evaluate the proposed therapy.
Better Preparation for INTERACT Meetings
While published FDA guidance documents may not provide all the answers, they can help researchers better prepare for INTERACT meetings by strengthening the rationale behind their model choices and enabling more targeted questions informed by previous regulatory guidance.
Improved Weight-of-Evidence Packages
FDA guidance for preclinical study design indicates how regulators value different sources and types of evidence. This can save significant time and resources, particularly when researchers can show that a 2-year rat study is unlikely to add value to a human carcinogenicity risk assessment2.
Improved Adaptation to a Changing Environment
The regulatory landscape is in constant flux, and recent shifts in expectations make early regulatory insight even more valuable during development. New approach methodologies (NAMs) are gaining momentum in preclinical work as ways to reduce reliance on animal testing and improve the human relevance of safety and efficacy data. The FDA's 2025 roadmap and 2026 draft guidance now explicitly recognize NAMs, but researchers still have limited insight into how regulators value and interpret NAM data3,4. Research that combines animal work with NAMs will likely become more commonplace, and understanding how regulators value these combinations will be crucial for success, particularly as FDA encourages parallel submission of both data types3.
Complete Response Letters
Since 2025, the FDA has been publishing complete response letters, including some for applications that were never approved, which gives sponsors a rare view of the reasons behind regulatory rejections5. Reviewing these letters can help teams spot recurring deficiencies, such as clinical, safety, or manufacturing gaps, and plan their programs to avoid them. While not directly relevant for early model selection, these resources offer another insight into regulatory considerations and can help sponsors anticipate how regulators judge a program as a whole from the earliest stages of planning.
One Platform for Study Design and Regulatory Insights
ModernVivo provides researchers with the information they need to design preclinical studies, drawing on published scientific literature alongside publicly available FDA guidance. Our platform synthesizes FDA review documents for drugs that have been evaluated, so teams can see how regulators have viewed comparable models and approaches before they finalize their study designs. Collectively, these capabilities help to remove risk, improve regulatory confidence, and set teams up for success from the start.
Gain regulatory insights for your study design today.
References
1. Manning ML, Thompson MD, Saber H, Maher VE, Crich JZ, Leighton JK. An FDA analysis of clinical hold deficiencies affecting investigational new drug applications for oncology products. Regul Toxicol Pharmacol. 2020;110:104511. doi:10.1016/j.yrtph.2019.104511
2. Center for Drug Evaluation and Research. S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals. November 1, 2022. Accessed October 12, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/s1br1-addendum-s1b-testing-carcinogenicity-pharmaceuticals
3. FDA O of the C. FDA Announces Plan to Phase Out Animal Testing Requirement for Monoclonal Antibodies and Other Drugs. FDA. May 28, 2025. Accessed October 12, 2026. https://www.fda.gov/news-events/press-announcements/fda-announces-plan-phase-out-animal-testing-requirement-monoclonal-antibodies-and-other-drugs
4. Center for Drug Evaluation and Research. General Considerations for the Use of New Approach Methodologies in Drug Development. July 24, 2026. Accessed October 12, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-use-new-approach-methodologies-drug-development
5. FDA O of the C. FDA Embraces Radical Transparency by Publishing Complete Response Letters. FDA. July 10, 2025. Accessed October 12, 2026. https://www.fda.gov/news-events/press-announcements/fda-embraces-radical-transparency-publishing-complete-response-letters