Executive Commitees of the European (ESTP), North American (STP),British (BSTP), French (SFPT), Indian (STP-I), Japanese Societies (JSTP)and the International Federation of Societies of Toxicologic Pathologists (IFSTP)
Contact address:
ESTP Committee Chair for Scientific Standards
Dr. Annette Romeike, Dipl.ACVP, FTA Pathologie
Covance Laboratories SAS
2-8, rue de Rouen
78440 PorchevilleFranceAndrew GrayGLP Operations Manager
Inspections and Standard Division
The Medicines and Healthcare Products Regulatory Agency
Market Towers
1 Nine Elms LaneLondon SW8 5NQ
November 15, 2013
Comments to “Draft OECD Guidance on the GLP Requirements for Peer Review of Histopathology”
Dear Mr. Gray,
The community of Toxicologic Pathologists has recently been informed of a new draft version of anOECD advisory document “Draft OECD Guidance on the GLP Requirements for Peer Review ofHistopathology.” It is our understanding that the OECD considers the current document to be a near
final version of the document elaborated by the OECD Working Group that was previously sharedwith the various international societies of Toxicologic Pathology (STPs) in July, 2010. The respective
STPs and the IFSTP (International Federation of Societies of Toxicologic Pathologists) had previously
provided comments on this document (gathered from their memberships) to the OECD Working
Group in October, 2010. It was anticipated that the pathology community would have additional
opportunity for comment once the document had moved to a more mature state. We have several
important concerns regarding the guidance document. We believe these concerns must be addressed
before such guidance is finalized if it is to be effectively instituted. Also, it is our understanding that it
is common practice for subject matter experts (in this case, practicing toxicologic pathologists) to be
included on any Working Group generating such guidance documents, and we think that the inclusionof such individuals would be of great benefit.
We appreciate that the OECD Working Group has significantly modified the previous 2010 draft
document. We recognize that part 1 (Background) of the current draft document adequately presents
the context of a peer review as proposed in the recent “Recommendations for Pathology Peer Review”(Morton et al.,Toxicologic Pathology, 2010). The Morton et al. publication has been endorsed by all
major toxicologic pathology organizations including the American Society of Toxicologic Pathology(STP), the European Society of Toxicologic Pathology (ESTP), the Japanese Society of ToxicologicPathology (JSTP), the British Society of Toxicologic Pathologists (BSTP), the French Society ofToxicologic Pathology, the Italian Society of Toxicologic and Experimental Pathology, the Society ofToxicologic Pathology— India, the Korean Society of Toxicologic Pathology, the Latin American
Society of Toxicologic Pathology, and the American College of Veterinary Pathologists.
The subsequent paragraphs 2 and 3 (GLP Requirements and Compliance) also largely refer to existing
best practices as described in the aforementioned Morton et al. publication and other documents listed
in the Reference section at the end of this letter (e.g. Peer Review Statement document, clear

designation of a Peer Review pathologist in the Study Plan, appointment of an expert group (PWG,Pathology Working Group) etc.). However, the OECD document goes on to list additional
expectations in the main body of the text which do not comply with recognized peer review bestpractices. These specifications have raised significant concerns in toxicologic pathology and quality
assurance communities, as well as GLP-compliant pharmaceutical and chemical toxicology test
facilities and contract research organizations. Some of these additional expectations lack clarity, seem
contradictory within the document, or dramatically change major aspects of conducting anddocumenting peer review activities for GLP studies. It is uncertain if this was the intention of thisdocument, but compliance with this draft OECD guidance document will require substantial
alterations in internationally accepted peer review processes. It is important that the expectations in
the guidance document are more clearly defined so as to be better understood by the groups
responsible for implementing the final OECD guidance. We also feel that it is important that any
expectations in the final guidance remain consistent across all international regulatory agencies.
Below we list some of our points of concern; note that this list is not comprehensive.
Major points of concern are:•Lack of clear distinction between prospective and retrospective peer review and clear
acknowledgment of different types of peer review during the reporting life-cycle.

•Requirement to appoint the peer reviewing pathologist as Principal Investigator if working
remotely from the Test facility (irrespectively of the peer review type and despite the fact thatthe peer review pathologist does not generate raw data or a contributor report (QC character ofa peer review) prior to finalisation of the Study pathologist’s report (2.3.)).

•Definition of histopathology slides as raw data, in contrast to current understandings andpractices communicated by authorities (FDA GLP Regulations, 21 CFR Part 58, 1987) (2.4.):
Histopathology slides are archivable specimens, according to the FDA GLP Regulations.

http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/NonclinicalLaboratoriesInspectedunderGoodLaboratoryPractices/ucm072706.htm•Inconsistencies and lack of clarity regarding both general expectations and the precise natureof documentation during the peer review and reporting life cycle. For example, section 2.10
indicates that “In most cases it will not be necessary to report in detail the outcome of the peer
review”; however both sections 2.7 and 2.10 indicate that “…if changes are required these areclearly documented and explained in the final report;”) . These statements are seeminglycontradictory. Due to the iterative and collaborative nature of peer review as summarized in
Morton et al, the majority of pathology peer reviews result in some modification of either thepreliminary study histopathology data tables or the draft study pathologist’s report prior to its
finalisation. In the majority of peer reviews, the primary and peer review pathologist reachconsensus on the histopathology findings and their overall interpretation before finalization ofdata and contributing scientist report. Therefore, the requirement to include in the final study
report a listing of all changes made to draft data/reports does not add value and has thepotential to create confusion in the final study report.

•Capability of the study director to assess expertise of the reviewing pathologist and the qualityof the peer review process (3.2.) without involvement of the Test Facility/Test Site Study
pathologist’s management.

The practice of peer review is strongly endorsed by the international Toxicologic Pathology
community, and we agree that for GLP compliance it is essential that “…peer review procedures areplanned, conducted, documented, and reported such that the integrity of the regulatory study is notcompromised and activities can be fully reconstructed and verified.”(4.1). However, we consider thatthe current document will not achieve this objective, given the number of shortcomings (mainly inpart 2 and 3), and the lack of acknowledgment of the variety of situations under which a rigorous peer2review can be conducted and regulated in test facilities and test sites. In our opinion, this guidanceshould be revised before final approval to provide clarity on expectations, and so as not to create
confusion for pathologists, study directors, quality assurance auditors, and test facility/sitemanagement if this draft is implemented in its current form.
In order to strengthen the histopathology peer review process in the pharmaceutical and chemicalindustry and contract research organisations, we strongly recommend that the OECD Working Groupassign recognized subject matter experts (practicing Toxicologic Pathologists) representing
international toxicologic pathology societies to assist in the preparation of the OECD Guidance on
the GLP Requirements for Peer Review of Histopathology. We feel important modifications to theguidance must be made to ensure effective institution and added value in the pathology peer review
process and report quality.
The Presidents of the ESTP, STP, BSTP, SFPT, JSTP and IFSTP thank you for the opportunity toreview these draft guidelines and hope that suggestions provided will be taken into consideration by
the OECD Working Group. The point of contact for this matter is: Annette Romeike, Dr med.vet.,
D.A.C.V.P. , ESTP Committee Chair for Scientific Standards (Tel. +33 6 22 16 58 87, email:annette.romeike@covance.com).

Dr. Frederic Schorsch
ESTP Chairman

Dr. Robert C. Sills,DVM,PhD,DACVPSTP President

Dr. Richard Haworth, D.Phil, DECVP, FRCPath
BSTP President

Dr. Katsumi Imaida, MD, PhD
JSTP President

S.K.Vijayasarathi, M.V.Sc.,Ph.D
STP-I President

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Dr. Erio Barale, Dr.med.vet.
SFPT President

Dr. Takanori Harada, DVM, PhD
IFSTP PresidentCc: Chairs of EFPIA Board and Executive Committee
Chairman of PhRMA Board

References
Morton, D., Sellers, R., Barale-Thomas, E., Bolon, B., George, C., Hardisty, J.F., Irizarry, A., McKay,J.S., Odin, M., Teranishi, M. (2010). Recommendations for pathology peer review. Toxicol Pathol,
DOI: 10.1177/0192623310383991.
Barale-Thomas, E., Bradley, A. (2009). Results of the “Peer review survey”: the report is open forcomments. Poster presented at the annual general meeting of the European Society of Toxicologic
Pathology, held September 15-18, 2009, The Hague, The Netherlands.
Japanese Society of Toxicologic Pathology (2009). Panel discussion: Regulatory perspective forpathology data. J Toxicol Pathol 22, 209-227.
McKay, J. S., Barale-Thomas, E., Bolon, B., George, C., Hardisty, J., Manabe, S., Schorsch, F.,
Teranishi, M., Weber, K. (2010). A commentary on the process of peer review and pathology datalocking. Toxicol Pathol 38, 508-510.
Tuomari, D.L., Elliott, G., Kulwich, B., Yarrington, J., Foillet, X., Geoly, F., Long, P. (2004). Societyof Toxicologic Pathology position on histopathology data collection and audit trail: compliance with
21 CFR parts 58 and 11. Toxicol Pathol 32, 122-123.
United States Federal Register (1987). Preamble to the good laboratory practice regulations. 52 (172),
September 1, 33768-33782.

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