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Best Practices for Histopathology Assessment in Preclinical Studies

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Best Practices for Histopathology Assessment in Preclinical Studies
Carol Meschter, DVM, Ph.D., DACVP

The preparation of the Pathology Report, whether a large report supporting a GLP toxicity study or a small research report, represents one of the most important phases of a preclinical study. Only a board-certified or board-qualified veterinary pathologist is qualified to assess preclinical histopathology.

Study Protocol Preparation

The study pathologist should be integral in the preparation of the study protocol; it is a good practice for the pathologist to be one of the signatories on the study protocol. Prior to the histologic slide assessment phase, the study pathologist should have access to the study protocol and all protocol amendments, pharmacokinetic/toxicokinetic data, clinical signs, body weight and food consumption data, clinical pathology data, organ weight data, necropsy observations, the relevant biology of the target molecule (e.g., tissue distribution and function of the target molecule, if known), and information about expected activity and known toxicity of the test article.

Pathology Report Specifications

The Pathology Report should generally be a stand-alone report that is signed by the pathologist and incorporated as an appendix to the main Study Report. The Study Director and Pathologist will also prepare a summary and assessment of the pathology for inclusion in the main report. The Pathology Report itself should include at least a title page, compliance statement, QAU statement, table of contents, summary, introduction, methods including any special or supplemental techniques, results, discussion and references. Tables (such as incidence tables, individual animal reports, and macroscopic-microscopic correlations) generated from computerized data acquisition systems are attached as appendices to the Pathology Report. Pictures may also be included.

The identification of the lesions and interpretation of the findings particularly in terms of identification the NOEL are most important. The Pathology Report should have a clear description of the treatment-related findings including mechanism, rational, incidence, and severity of lesions. If possible, these findings should be related to dose exposure as well as clinical observations and macroscopic necropsy findings. Secondary lesions: lesions that develop as a result of the primary lesions should be also be identified and interpreted. Background or spontaneous lesions should also be identified. It is also important to determine if the test article induces an increase in the incidence and/or severity of background lesions separately from primary test article-related lesions.

Histopathology Assessment at CBI

At CBI, our Pathology Reports are prepared in accordance with the recommendations of the Society of Toxicologic Pathologists (STP) for Best Practices for Reporting Pathology Interpretations within GLP Toxicology Studies. We have pathologists on staff that provide expert and detailed histopathologic assessment of tissues and correlate the findings to disease or toxicologic mechanisms. Our pathology reports are comprehensive, formatted according to guidelines of the STP, and provide incidence tables, individual animal reports, statistics, and an integrated discussion. Digital image analysis and photomicroscopy is also available.

To learn more about the histopathology services at CBI, visit www.compbio.com/histopathology.php.


Morton, D, et al: Best Practices for Reporting Pathology Interpretations with GLP Toxicology Studies. ToxPath 34 (6):806-809, 2006

Crissman JW, et al. Best Practices Guideline; Toxicologic Histopathology.  Tox Path 32:126-131, 2004

About the Author

Carol Meschter, DVM, Ph.D., DACVP
Dr. Meschter is a founder of Comparative Biosciences, Inc. Previously, she was in the Investigative Toxicology Group at Hoffmann-LaRoche, Nutley, NJ, and was the Director of the Research Animal Facility at the American Health Foundation in Valhalla, NY. As a board-certified veterinary pathologist, Dr. Meschter brings fifteen years of experience in the pharmaceutical industry, primarily in toxicology, pathology, preclinical development, discovery support, and preclinical pharmacology. She is knowledgeable in early phase drug development from discovery to NDA, with technical expertise in pathology, pharmacology, efficacy modeling, and pharmacokinetics. She is a scientific editorial reviewer for Toxicologic Pathology, Veterinary Pathology, AVMA Journal, AJVR, J Applied Immunology, and has over 100 publications.