Peer Review in Toxicologic
Pathology
10th ESTP Congress 2012
Stresa, Italy○10th ESTP Congress
September 11-14, 2012
Stresa, Italy

Current Situation for Pathology
Peer Review in Japan
September 14, 2012
Taki Harada, DVM, PhD
Peer Review Ad hoc Working GroupThe Japanese Society of Toxicologic Pathology

Outline of Presentation
1.

Regulatory Agencies in Japan

2.

Current Pathology Peer Review （PPR)in Japan3.

Current Definition of Pathology Raw Data

4.

Current Reporting Procedures in Japan

5.

JSTP Actions to PPR

6.

New Draft Proposal for PPR by PMDA

7.

JSTP Position on PPR

1. Regulatory Agencies in Japan
Subjects

Guidelines

Risk Assessment

Pharmaceuticals:
Synthetic

MHLW (2000)

PMDAHerb

MHLW*

PMDA

Food additives:

MHLW (1996)

Food Safety Commission

Health foods:

MHLW*

MHLW subcommittee

SyntheticMAFF (2000)

Food Safety Commission

Microbial

MAFF (1997)

Food Safety Commission

Veterinary drugs

MAFF (1985)

Food Safety Commission

METI/MHLW/ME (2001)

Food Safety Commission

Agrochemicals:Industrial chemicals:* : Not specified, determined on case-by-case basis
MHLW = Ministry of Health, Labor and Welfare
MAFF = Ministry of Agriculture, Forest and FisheriesMETI = Ministry of Economy, Trade and Industry
ME= Ministry of the Environment
PMDA = Pharmaceuticals and Medical Devices Agency

2. Current Pathology Peer Review in Japan・ Pathology peer review (PPR) is recommended to be
conducted but not required by any of regulatory
agencies in Japan.
・ Only Pharmaceutical and Medical Devices Agency(PMDA) proposed a guidance in 2006, “PPR bypathologists from sponsors should be conducted
after data locking”.
・ Consequently, sponsor PPR for pharmaceuticals
has been being conducted after pathology data isfixed in accordance with the proposed guidance
2006 by PMDA.

Current PPR Procedures in Japan
Study Pathologist (SP)(reads slide)

Data locking
Internal PPR

Sponsor PPR

Findings

Findings

Work sheet

Work sheet signed
and dated by SP(Raw data)

Revised version

Findings
If any changes,
Document the history

Study Director(SD)Final Report3. Current Definition of Pathology Raw
Data in Japan・ Pathology raw data is defined as findings describedin the work sheets signed and dated by Study
Pathologist (SP) in Japan.
・ SP submits incidence data (Tables) and individualfindings (Appendices) to Study Director after thedata is finalized. However, pathology report singedand dated by SP is customarily not issued.
SPData generated by SPWorksheet(signed/dated)
ReportSD4. Current Reporting Procedures in Japan・ All the data generated during the conduct of a
toxicological study are submitted to the Study
Director (SD). Only SD prepare the final reportbased on the results gathered from each section.
・ Therefore, Study Pathologist (SP) is not required toprepare a pathology report. Only pathology datasinged and dated by SP is required to be submittedto SD.
Study conductAll datageneratedSD
Only SD has aresponsibility
to describe the final report5. JSTP Actions to Pathology Peer Review
・ International panel discussion on regulatory perspective forpathology data was held at the 25th JSTP Annual Meeting in2009. It was recognized that the timing of PPR and definitionof raw data considerably differ among US, Europe and Japan.
・ After a draft OECD guidance on PPR was proposed, the JSTP
Peer Review Ad hoc Working Group discussed about thecontent with all members of the JSTP and consequently
decided to endorse the STP position.
・ In 2010, the JSTP and other relevant parties had a couple offace to face meetings with PMDA and recommended that PPRprior to data locking would be more suitable to improve thequality of pathology data.

6. New Draft Proposal for PPR by PMDA
・ PPR is not mandatory to nonclinical studies of pharmaceuticalproducts, but if PPR is carried out, then it is subject of GLP
inspection.
・ At the moment, PMDA considers that pathology raw data is thereport or data signed and dated by the study pathologist.
・ PPR before or after data locking would be acceptable either way,
but PPR by pathologists outside from sponsors or academia may berequired to ensure the transparency of review process and to be
described in the protocol if the conduct is scheduled in advance.
・ In that case, the name of the pathology peer reviewer and reviewed
organs with disagreement should be described in the final report.
・ The report or data generated by the peer reviewer should bearchived together with other study documents.

7. JSTP Position on Pathology Peer Review
・ The JSTP basically agrees with the new draft
proposal by PMDA, although we need further
discussions in details before it is finalized.
・ In principle, the JSTP position is consistent
with that of STP which is shown in“Recommendations for Pathology Peer Review”
published in Toxicologic Pathology in 2010.

Taki

Dream forever