Experimental Pathology Laboratories, Inc. (EPL) meets or exceeds current FDA guidelines following the release of “Pathology Peer Review in Nonclinical Studies: Questions and Answers, Guidance for Industry” document in December 2021 (https://www.fda.gov/media/129533/download)
At EPL we pride ourselves on providing our clients with not only the best services possible, but also with the up to the date regulatory compliance for all GLP activities as appropriate to our histology and histopathology services. In this instance, this informative guidance document addresses some of the more common questions/concerns regarding the management, conduct, documentation and reporting of pathology peer reviews as briefly discussed in this blog. The pathology component of a nonclinical study involves the evaluation of organ tissue sections resulting in diagnoses to determine if there is a test article-related effect. The interpretation of the diagnoses and the relationship to the test article also relies on other study data (e.g. gross findings, organ weights, clinical pathology parameters, etc.) and the experience of the pathologist (e.g. variations of normal morphology in the test species, concurrent controls, historical controls, artifacts from tissue collection or tissue processing, and relevant pharmacology and literature).
Why peer review a nonclinical study? There can be many reasons to consider a peer review but the most common is related to further increase the quality, accuracy and consistency of the pathology diagnoses and interpretations within a study and across studies. In many instances the peer reviewing pathologist has a specific expertise relevant to the study findings. Peer reviews can be conducted prior to (contemporaneous peer review) or after (retrospective) finalization of the study pathologist’s report. In either instance it is important that the peer-review process be well documented and transparent since it becomes a component of a GLP toxicology study. At EPL we have pathologists with extensive pathology experience in the review of nonclinical studies and most of our pathologists are recognized leaders in the discipline of toxicologic pathology either as species, organ system, or mechanism of action content experts to help ensure that you are receiving the most accurate pathology data for decision making in your development program. EPL has a proprietary software program that makes the review process efficient and transparent, with compete documentation of what was reviewed and how any differences between the study pathologist and the peer review pathologist were resolved. EPL has written procedures in the form of SOPs for the conduct, documentation, and reporting of peer reviews that make the process GLP compliant and, a transparent and seamless procedure.
Following a contemporaneous peer review, the peer review statement indicates whether the peer review pathologist agrees with the report based on their review. If the study pathologist and peer review pathologist cannot reach consensus, there are processes to be considered (e.g. convening a pathology working group which is a panel of experienced pathologists to provide diagnoses for disputed findings) to resolve differences. EPL is an international leader in the conduct and reporting of pathology working groups (subject of a future EPL blog).
This blog only briefly discusses some of the more important aspects of peer reviews as there may be other reasons for you to consider conducting peer reviews on your nonclinical studies. Please contact EPL if you have any questions or would like more information on peer review or pathology-related services offered by EPL.
Additional references related to peer review and pathology working groups which can be provided upon request:
Crissman, J. W., Goodman, D. G., Hildebrandt, P. K., Maronpot, R. R., Prater, D. A., Riley, J. H., Seaman, W. J., and Thake, D. C. (2004). Best practices guideline: Toxicologic histopathology. Toxicol Pathol 32, 126–31.
Fikes, J. D., Patrick, D. J., Francke, S., Frazier, K. S., Reindel, J. F., Romeike, A., Spaet, R. H., Tomlinson, L., and Schafer, K. A. (2015). Scientific and Regulatory Policy Committee Review: Review of the Organisation for Economic Co-operation and Development (OECD) Guidance on the GLP Requirements for Peer Review of Histopathology. Toxicol Pathol, 43, 907-914
Mann, P. C., and Hardisty, J. F. (2013). Peer review and pathology working groups. In Handbook of Toxicologic Pathology (W. M. Haschek, C. G. Rousseaux, M. A. Wallig, B. Bolon, R. Ochoa, and B. W. Mahler, eds.), 3rd ed., pp. 551–64. Elsevier, New York.
Morton, D., Sellers, R., Barale-Thomas, E., Bolon, B., George, C., Hardisty, J., Irizarry, A., McKay, J. S., Odin, M., and Teranishi, M. (2010). Recommendations for pathology peer review. Toxicol Pathol 38, 1118–27