Regulatory Acceptance of Digital Pathology for Nonclinical Toxicology Studies

How Rigorous GLP Validation Answers the Digital Pathology Questions That Matter Most

For years, two questions have followed every conversation about adopting digital pathology for primary toxicologic pathology evaluation.

Both are the right questions. And the scientific evidence, including a recently published validation study in Regulatory Toxicology and Pharmacology, shows that rigorous answers to both now exist.

Digital pathology for nonclinical toxicology is no longer an emerging concept. It is a scientifically proven, validated, regulatory‑accepted approach to primary histopathological evaluation.

The Validation Question: How Do You Prove It’s Safe to Use?

The foundation of any credible argument for whole‑slide imaging (WSI) in a Good Laboratory Practice (GLP) environment is non‑inferiority testing, which is specifically developed to determine whether digital microscopy performs within an acceptable diagnostic margin compared to conventional light microscopy.

In a multi‑site validation published in Regulatory Toxicology and Pharmacology (Żuraw et al., 2026), we described the GLP validation of a cloud‑based digital pathology platform, Patholytix by Deciphex, Ltd., for use in primary pathology evaluation of nonclinical toxicology studies. This validation represents the first fully integrated, multi‑site GLP validation of a single, cloud‑based, WSI platform for primary toxicologic pathology evaluation.

Whole-Slide Images for GLP Digital Toxicologic Pathology
This article details how GLP‑validated whole‑slide imaging now supports primary evaluation at scale, underscoring the practical value of digital pathology.
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The scientific core of the validation was a rigorous user acceptance testing (UAT) process conducted by two board‑certified veterinary pathologists — one credentialed by the European College of Veterinary Pathology (ECVP) and one by the American College of Veterinary Pathology (ACVP), at two independent timepoints. The critical microscopic features they were required to identify on WSI were not arbitrarily selected. The list was developed from a survey of more than 150 pathologists and cross‑referenced with the published proceedings of the 7th ESTP International Expert Workshop (Schumacher et al., 2021).

These features included some of the most diagnostically demanding findings in toxicologic pathology: mitotic figures, intracytoplasmic basophilic granules, single cell necrosis, axonal degeneration, and bacteria, among others. The validation set encompassed six species (small and large animal), multiple staining techniques, including hematoxylin and eosin, immunohistochemistry, and special histochemical stains and tissues drawn from the standard core list for repeat‑dose toxicity and carcinogenicity studies.

The answer to the pathologist’s question, “Will I miss a subtle lesion?”, is addressed directly by this methodology. If the most challenging diagnostic features are demonstrably visible and interpretable in a whole‑slide image by independent, board‑certified pathologists across multiple species and stain types, the concern is not eliminated through assumption – it is addressed through evidence.

The Risk Question: What Could Still Go Wrong?

Validation testing alone cannot anticipate every operational scenario. This is why a comprehensive risk assessment is an essential, and frequently underappreciated, component of any GLP‑compliant digital pathology implementation.

The risk assessment described by Żuraw et al. (2026) evaluated hazards according to three components: impact severity if the risk is realized, probability of occurrence, and probability of detection. Each combination of risk class and detection probability resulted in a defined risk category, with corresponding procedural controls documented in system‑specific Standard Operating Procedures.

For digital pathology specifically, identified risks included the possibility of a whole‑slide image being of insufficient quality to visualize subtle lesions, and the risk of tissue being out of focus on the scan. Mitigation strategies were not left to informal practice: they included visual and automated image inspection at the time of scanning, verification by the study pathologist during evaluation, and defined rework protocols when image quality was inadequate.

This structured approach reflects a principle that is easy to overlook when evaluating digital pathology systems: a validated system is not one where nothing can go wrong. It is one where potential failure modes have been identified, scored, and controlled with documented procedural safeguards.

The Regulatory Question: Has Acceptance Already Arrived?

For pharmaceutical and biotech companies, the concern about regulatory acceptance is understandable. Introducing new technology into IND‑enabling studies carries risk if regulators are uncertain about it.

The evidence from both regulatory guidance and real‑world submissions suggests that acceptance is not forthcoming — it is already here.

The U.S. Food and Drug Administration has published guidance specifically on the use of whole‑slide imaging in nonclinical toxicology studies (McDorman et al., 2024), providing a clear regulatory framework for GLP‑compliant digital pathology workflows, including requirements for retaining both digital images and original glass slides. By 2019, various WSI systems had already received FDA clearance or been adopted as laboratory‑developed tests for primary diagnostics in human pathology (Smith et al., 2022).

The French National Agency for the Safety of Medicines and Health Products (ANSM) provided specific feedback on our validation, focusing on two priorities: confirmation of WSI and label immutability through test scripts, and independent verification of cloud‑hosted data integrity by test facility management. These were addressed directly, strengthening the validation’s alignment with both FDA data protection guidance and OECD 17 requirements for computerized systems.

The practical outcome speaks clearly. Since May 2023, more than 600 GLP toxicology studies have been conducted using whole‑slide imaging at Charles River (it was more than 300 at the time the manuscript was written), with multiple regulatory submissions incorporating WSI‑generated pathology data. Regulators are not only aware of these submissions — they are accepting them.

What This Means for Drug Development

The ability to conduct primary histopathological evaluation digitally, without the logistical burden of shipping glass slides or requiring pathologist travel, has meaningful implications for how drug development organizations operate. Global collaboration becomes structurally easier. Multi‑site workflows become more consistent. Data mining and image analysis capabilities become accessible in ways that glass‑based workflows do not support.

These are not speculative benefits. They are operational realities already in practice across hundreds of GLP toxicology studies. There’s only one question left for your organization to answer: will you take advantage of it?

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This article is based on findings published in: Żuraw A, Staup M, Bertrand L, Cyr F, Deiters J, Rudmann D. Use of whole-slide images for primary pathology evaluation of non-clinical toxicology studies in a GLP-validated environment. Regulatory Toxicology and Pharmacology. 2026;168:106062. https://doi.org/10.1016/j.yrtph.2026.106062