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Current Status and Issues Current Status and Issues With Global Acceptance of ICHWith Global Acceptance of ICH

Jurij Petrin, M.D.Jurij Petrin, M.D.

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ICH HistoryICH History

Meeting in April 1990, hosted by the EFPIA in Meeting in April 1990, hosted by the EFPIA in BrusselsBrusselsRepresentatives of the regulatory agencies and Representatives of the regulatory agencies and industry associations of Europe, Japan and the industry associations of Europe, Japan and the USAUSAICH Steering Committee establishedICH Steering Committee establishedMeets at least twice a year, with the location Meets at least twice a year, with the location rotating between the three regions rotating between the three regions

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Original ICH PartiesOriginal ICH Parties

The regulatory bodies and the researchThe regulatory bodies and the research--based industry based industry in the European Union, Japan and the USA:in the European Union, Japan and the USA:

EC (EMEA)EC (EMEA)--EFPIAEFPIAMHLWMHLW--JPMAJPMAFDAFDA--PhRMAPhRMA

Observers:Observers:WHOWHOEFTA EFTA Canada Canada

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ICH AdministrationICH Administration

ICH Steering CommitteeICH Steering CommitteeICH SecretariatICH SecretariatMembership of the ICH Steering CommitteeMembership of the ICH Steering Committee

Two seats by each member Two seats by each member IFPMA provides the Secretariat and participates as a IFPMA provides the Secretariat and participates as a nonnon--voting member of the Steering Committeevoting member of the Steering CommitteeThe Observers attend the ICH Steering Committee The Observers attend the ICH Steering Committee Meetings as nonMeetings as non--voting participantsvoting participants

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NonNon--ICH MarketsICH Markets

All other countries not mentioned beforeAll other countries not mentioned beforeSpecific situation in Europe due to EU expansionSpecific situation in Europe due to EU expansionThe The ““officialofficial”” link to all other markets link to all other markets -- WHOWHOIndustry basically expected ICH to be followed Industry basically expected ICH to be followed everywhereeverywhereMost ICH guidelines accepted worldwide but Most ICH guidelines accepted worldwide but with exceptionswith exceptions

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Status of ICH Global Acceptance Status of ICH Global Acceptance

ICH MembersICH MembersNon ICH MembersNon ICH Members

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ICH MembersICH Members

Harmonization often incomplete:Harmonization often incomplete:CTD format differencesCTD format differences

Module 1 region specificModule 1 region specificGaiyoGaiyoEurope: Expert Reports and tabulated summaries Europe: Expert Reports and tabulated summaries are required, and written summaries are are required, and written summaries are recommendedrecommendedSpecific NDA guidelines in the USSpecific NDA guidelines in the USPaper sizePaper sizeEtc.Etc.

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ICH MembersICH Members

Harmonization often incomplete (contHarmonization often incomplete (cont’’d):d):Differences in drug developmentDifferences in drug development

Placebo versus active comparatorPlacebo versus active comparatorNumber and type of patientsNumber and type of patientsSpecificities in Japan (full development or bridging)Specificities in Japan (full development or bridging)

Different technical informationDifferent technical informationCMCCMC

Compliance with local pharmacopoeiasCompliance with local pharmacopoeiasManufacturing (GMP information)Manufacturing (GMP information)

Different review procedures, timelines, etc.Different review procedures, timelines, etc.

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Non ICH CountriesNon ICH Countries

No official role in the ICH processNo official role in the ICH processExpected to simply implement and follow ICH Expected to simply implement and follow ICH guidelinesguidelinesMost general guidelines acceptedMost general guidelines acceptedCertain exemptionsCertain exemptions

EE--55ACTDACTDASEAN stability requirementsASEAN stability requirementsGMP validationGMP validationEtc. Etc.

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ICH EICH E--5:Ethnic Factors in the 5:Ethnic Factors in the Acceptability of Foreign Clinical DataAcceptability of Foreign Clinical Data

Status of Implementation (Step 5)Status of Implementation (Step 5)

EU: Adopted by CPMP, March 1998, issued as EU: Adopted by CPMP, March 1998, issued as CPMP/ICH/289/95CPMP/ICH/289/95Japan: Adopted August 98, PMSB/ELD Japan: Adopted August 98, PMSB/ELD Notification No. 672, PMSB Notification No739Notification No. 672, PMSB Notification No739USA: Published in the Federal Register, Vol. 63, USA: Published in the Federal Register, Vol. 63, No. 111, June 10, 1998, page 31790 in force No. 111, June 10, 1998, page 31790 in force September 98September 98

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Main Points of the EMain Points of the E--55

Most drugs are not ethnically sensitiveMost drugs are not ethnically sensitiveEthnic populations classified as Ethnic populations classified as

AsianAsianBlackBlackCaucasianCaucasian

Assessment of ethnic sensitivity made from Assessment of ethnic sensitivity made from bridging data in full clinical data packagebridging data in full clinical data packageBridging study may be carried out in a new Bridging study may be carried out in a new ethnic population if initial data assessment ethnic population if initial data assessment indicates ethnic sensitivity (Appendix D)indicates ethnic sensitivity (Appendix D)

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Current Issues With Bridging Current Issues With Bridging StudiesStudies

Asia only Asia only Some authorities more frequently Some authorities more frequently demanding data on ethnical differences demanding data on ethnical differences than othersthan others

JapanJapanKoreaKoreaTaiwanTaiwan

Some others Some others ““observersobservers””

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Recent developmentsRecent developments

Literature review Literature review (J (J ClinClin PharmacolPharmacol, Sept 2003), Sept 2003)

FDA Draft Guideline (January 2003)FDA Draft Guideline (January 2003)Attempt to revise the EAttempt to revise the E--5 Guideline was 5 Guideline was refusedrefusedQuestions and answers Questions and answers –– ICH Steering ICH Steering Committee (February 2003)Committee (February 2003)

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US FDAUS FDAJanuary 2003 January 2003 –– Draft Draft ““Guidance for Industry Guidance for Industry Collection of Race and Ethnicity Data in Clinical Collection of Race and Ethnicity Data in Clinical TrialsTrials””

A standardized approach for collecting race and ethnicity A standardized approach for collecting race and ethnicity information in clinical trials conducted in the United States information in clinical trials conducted in the United States and abroad for certain FDA regulated products. and abroad for certain FDA regulated products.

Developed by the Race and Ethnicity Working Group from Developed by the Race and Ethnicity Working Group from the Office of the Commissioner, the Center for Biologics the Office of the Commissioner, the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER) of the Food and Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA). Administration (FDA).

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US FDAUS FDA

Draft Guideline Recommendations:Draft Guideline Recommendations:consistency in data collection requiredconsistency in data collection requireduse of a twouse of a two--question formatquestion formathave trial participants selfhave trial participants self--report their racial and report their racial and ethnic category to enhance consistency ethnic category to enhance consistency individuals should be permitted to designate a individuals should be permitted to designate a multiracial identity. multiracial identity.

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Studies Performed in the USStudies Performed in the US

Draft Guideline Recommendations:Draft Guideline Recommendations:

For For ethnicityethnicity, the FDA recommends the following minimum , the FDA recommends the following minimum choices be offered: choices be offered:

Hispanic or LatinoHispanic or LatinoNot Hispanic or LatinoNot Hispanic or Latino

For For racerace: : American Indian or Alaska NativeAmerican Indian or Alaska NativeAsianAsianBlack or African AmericanBlack or African AmericanNative Hawaiian or Other Pacific IslanderNative Hawaiian or Other Pacific IslanderWhite White

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Studies Performed Outside of the USAStudies Performed Outside of the USAFDA recognizes that the categories for race and ethnicity FDA recognizes that the categories for race and ethnicity were developed in the United States and that these were developed in the United States and that these categories may not adequately describe racial and ethnic categories may not adequately describe racial and ethnic groups in foreign countries. groups in foreign countries.

For ethnicity:For ethnicity:Hispanic or Latino Hispanic or Latino Not Hispanic or Latino Not Hispanic or Latino

For race:For race:American Indian or Alaska Native American Indian or Alaska Native Asian Asian Black, of African heritage Black, of African heritage Native Hawaiian or Other Pacific Islander Native Hawaiian or Other Pacific Islander White White

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ASEANASEAN

Harmonization ongoingHarmonization ongoingTwo main issues in Two main issues in ““conflictconflict”” with ICH:with ICH:

ACTDACTDRegional ASEAN stability Regional ASEAN stability

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GMP HarmonizationGMP Harmonization

GMP Guide for Active Pharmaceutical GMP Guide for Active Pharmaceutical IngredientsIngredientsEWG was expanded: EWG was expanded:

Six ICH parties and the ObserversSix ICH parties and the ObserversExperts representing IGPA (generics industry)Experts representing IGPA (generics industry)WSMI (self medication industry)WSMI (self medication industry)PIC/SPIC/SRepresentatives from China, India and AustraliaRepresentatives from China, India and Australia

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Other GMP IssuesOther GMP Issues

Manufacturing validation Manufacturing validation –– TaiwanTaiwanRequirements over and beyond ICH Requirements over and beyond ICH Discussions ongoingDiscussions ongoing

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Global Cooperation GroupGlobal Cooperation Group

Subcommittee of the ICH Steering Committee Subcommittee of the ICH Steering Committee (formed 1999)(formed 1999)Purpose: ICH information source for nonPurpose: ICH information source for non--ICH ICH countriescountriesMembership:Membership:

One member from each of the six ICH membersOne member from each of the six ICH membersSecretariat (IFPMA)Secretariat (IFPMA)Two observers (WHO, Canada)Two observers (WHO, Canada)

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GCG PrinciplesGCG Principles

Serves as a resource for information and dataServes as a resource for information and dataWorks as closely as possible with WHO and other Works as closely as possible with WHO and other international organizationsinternational organizationsWill not cause or require any change to the current ICH Will not cause or require any change to the current ICH structure or procedures of operationstructure or procedures of operationICH Guidelines will be used as the basis of ICH Guidelines will be used as the basis of ICHICH’’ssresponse whenever information is requestedresponse whenever information is requestedGCG will provide information upon request from nonGCG will provide information upon request from non--ICH ICH countries and will make information available about the countries and will make information available about the existence of the ICH web site, the address for existence of the ICH web site, the address for communications, and related informationcommunications, and related information

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ConclusionConclusion

ICH is the current global drug development ICH is the current global drug development standardstandardHarmonization not complete even within the ICH Harmonization not complete even within the ICH membersmembersDrug development is increasingly global and that Drug development is increasingly global and that makes nonmakes non--ICH countries important playersICH countries important playersGCG is the first attempt to bring ICH to these GCG is the first attempt to bring ICH to these countries in a more organized waycountries in a more organized wayMore work lies aheadMore work lies ahead