Quality Overall Summary Grounds for Revision - NIHS

1 Quality Overall SummaryQuality Overall SummaryGrounds for RevisionGrounds for RevisionJean-Louis ROBERT, ROBERT, Health LaboratoryNational Health LaboratoryLuxembourg (EU)Luxembourg (EU)Module not part of CTD CTDM odule 2{CTD Table of Table of from ICH CTD QOSE xtract from ICH CTD QOS (1) (1) The Quality Overall Summary (QOS) is aThe Quality Overall Summary (QOS) is asummary that follows the scope and thesummary that follows the scope and theoutline of the Body of Data in Module 3. Theoutline of the Body of Data in Module 3. TheQOS QOS should not include information, data orshould not include information, data orjustification that was not already included injustification that was not already included inModule 3 Module 3 or in other parts of the CTD. or in other parts of the from ICH CTD QOSE xtract from ICH CTD QOS (2) (2) The QOS should include sufficient information fromThe QOS should include sufficient information fromeach section to provide the Quality reviewer witheach section to provide the Quality reviewer withan overview of Module 3.}

2 The QOS should alsoan overview of Module 3. The QOS should alsoemphasise critical key parametersemphasise critical key parameters of the product of the productand and provide, for instance, justificationprovide, for instance, justification in cases in caseswhere guidelines were not followed. The QOSwhere guidelines were not followed. The QOSshould include a discussion of key issues thatshould include a discussion of key issues thatintegrates information from sections in the Qualityintegrates information from sections in the QualityModule and supporting information from otherModule and supporting information from otherModules ( qualification of impurities viaModules ( qualification of impurities viatoxicological studies discussed under the CTD-Stoxicological studies discussed under the CTD-Smodule), including cross-referencing to volume andmodule), including cross-referencing to volume andpage number in other number in other from ICHE xtract from ICH CTD QOS (3) CTD QOS (3)

3 This QOS normally should This QOS normally should not exceed 40not exceed 40pages of text, excluding tables and figurespages of text, excluding tables and For biotech products and productsbiotech products and productsmanufactured using more complexmanufactured using more complexprocessesprocesses, the document could be longer, the document could be longerbut normally should not exceed but normally should not exceed 80 pages80 pages of oftext (excluding tables and figures).text (excluding tables and figures).QOS current situationQOS current situation EU/US:EU/US: Part of application filePart of application file True summaryTrue Summary Not the main basis for the assessment ofNot the main basis for the assessment ofthe application file for MA, used asthe application file for MA, used asintroductory documentintroductory document Module 3 is assessedModule 3 is assessedQOS current situationQOS current situation Japan:Japan: QOS driven by review processQOS driven by review process Main basis for the assessmentMain basis for the assessment Module 3 is used if more information isModule 3 is used if more information isrequiredrequiredQOS Informal Working Group 4 QOS Informal Working Group 4 June 2006 June 2006 Objective:Objective:To identify the future utility of the QOSTo identify the future utility of the QOSQOS Revision : Agreement (1)QOS Revision .

4 Agreement (1) Objective of the proposed Revision :Objective of the proposed Revision :To use QOS as a principal assessmentTo use QOS as a principal assessmenttool;tool;placing key information into key information into Revision : Agreement (2)QOS Revision : Agreement (2) Should be prepared in such a way that it facilitatesShould be prepared in such a way that it facilitatesscientific risk-based assessment and that the needscientific risk-based assessment and that the needto look into Module 3 is look into Module 3 is minimised. A well prepared QOS will present all the informationA well prepared QOS will present all the informationnecessary to make an approval decision resulting innecessary to make an approval decision resulting instream-lining of the approval process, benefitsstream-lining of the approval process, benefitsdepend on the Quality of the on the Quality of the document.

5 Scope: Scope: NCEsNCEs and Biotech products and Biotech products Current Initiative is moving towards the direction ofCurrent Initiative is moving towards the direction ofthe present use of the Japanese QOS present use of the Japanese QOS approach. The Revision of QOS may facilitate harmonisation ofThe Revision of QOS may facilitate harmonisation ofthe Revision : BenefitQOS Revision : Benefit Regulators:Regulators: concentration on the most importantconcentration on the most importantinformation,information, better use of use of resources. Industry:Industry: will facilitate the submission of a single dossierwill facilitate the submission of a single dossierin the 3 ICH the 3 ICH Revision :QOS Revision :further discussion pointsfurther discussion points Identification of the type of informationIdentification of the type of informationnecessary in Module 2 (QOS);necessary in Module 2 (QOS); Guidance document on content needed orGuidance document on content needed or Guidance document on format?

6 Guidance document on format? Procedure: EWG versus IWGP rocedure: EWG versus IWG Change of the title QOS ?Change of the title QOS ? Implications on CTD-Q ?Implications on CTD-Q ? Implications on e-CTD (minor impactImplications on e-CTD (minor impactanticipated)anticipated) Regional consequences:Regional consequences:Change of legislation? Regional clarificationChange of legislation? Regional Revision : Relationship to Module 3 QOS Revision : Relationship to Module 3 Illustrative Examples (draft proposal)Illustrative Examples (draft proposal) QOSQOS Drug prod. development/designDrug prod. development/design Drug substance/Drug Product manufactureDrug substance/Drug Product manufacture Impurities profile and qualificationImpurities profile and qualification Analytical procedures + validation (in tabularAnalytical procedures + validation (in tabularform)form) Stability (in form of figures / tables,Stability (in form of figures / tables,commitments)commitments) Module 3 Module 3would contain the supporting information pluswould contain the supporting information plusstudies, , EU PositionQOS EU Position Can see the advantage of using a QOS as aCan see the advantage of using a QOS as aprimary assessment assessment tool.

7 Module 3 should still be part of theModule 3 should still be part of theapplication dossier for dossier for MA. Future discussion will be necessary in orderFuture discussion will be necessary in orderto identify the exact identify the exact Revision : Future ActivitiesQOS Revision : Future Activities Discussion will continue in November 2006 Discussion will continue in November 2006 Clarification of the different issues raisedClarification of the different issues raised Content or format documentContent or format document Implications on e-CTDI mplications on e-CTD Verification of legal implicationsVerification of legal implicationsQuality Overall SummaryQuality Overall SummaryMHLW ReviewerMHLW Reviewer ssExperienceExperienceMayumi SHIKANO,Mayumi SHIKANO, andPharmaceuticals andMedical Devices AgencyMedical Devices AgencyContentContentss Japanese NDA Dossier and QOS Current Practice and Experiencewith QOS in Japan Japanese NDAJ apanese NDAD ossier and QOSD ossier and QOSJ apanese NDA DossierJapanese NDA DossierApplicationApplicationFormFormCTD +Application Form andApplication Form andApproval MattersApproval Matters Contents provided in the NDAapplication form are dealt with as matters subject to approval.

8 Contents described in approval letterare legal binding approval matters. Contents described in QOS (module 2)and module 3 are not legal MattersApproval Matters General name (for active ingredient) Brand name Composition Dosage and administration Manufacturing process, including controlof materials Indications Storage condition and shelf-life Specifications and analytical proceduresRelationship between Relationship between Application FormApplication Formandand CTD DocumentsCTD Analytical Validation of analytical Batch Justification of specification Specifications Analytical procedures PharmaceuticalDevelopment Manufacturing Process batch analyses Justification form (in Japanese)Module 2 (QOS)(in Japanese)Module 3 (in Japaneseor English)Analyticalprocedures(JP style) &acceptancecriteriaManufacturingprocessR aw data Current Practice andCurrent Practice andExperienceExperience with QOSwith QOSin Japanin JapanNDA Review Process in JapanNDA Review Process in JapanMHLWMHLWR eport (2)Report (2)Review TeamDiscussionInterview Review Meeting on Key IssuesApplicantApplicant PMDA PMDAI nterviewDiscussionCommitteeson New DrugsReview ConclusionReview ConclusionApproval or not ApprovalAdviseReport (1)Report (1)M 1&2M 3M 1,2,&3Q&AM 1&2 (revised)Report (1)&(2)Report (1)&(2)Review ConclusionReview ConclusionReport (1)Report (1)ExpertsPAFSCPAFSCM odule 2 as Key ReviewModule 2 as Key ReviewDocuments in JapanDocuments in Japan Without IND, comprehensive QOS helps reviewersto understand Quality of the product quickly.

9 Reviewers review QOS and then narrow down intoModule 3 when they need more detailedinformation. Reviewers require Applicant to revise ApplicationForm reflecting Analytical Procedure andManufacturing Process described in revised QOS. Module 1 and 2 together with review reportswritten by reviewers are evaluated inPharmaceutical Affairs and Food Sanitation ofCharacteristics ofJapanese QOSJ apanese QOS Within CTD guideline Expected to summarize critical data in module3 into QOS, along with sufficient discussion onevery critical point for ensuring the Quality ,efficacy and safety of the drug Include many figures and tables whichsummarize critical data Include narrative Summary and/or discussion Should be written in Japanese :Tables & Figures may be in EnglishBenefits from Japanese QOSB enefits from Japanese QOS QOS helps efficient review; reviewers canunderstand the characteristics of the drugwithin a short period QOS can be a vehicle for knowledgemanagement in regulatory authorities andin industry Writing Japanese style QOS takessignificant time and energy.

10 BUT it helpsthe applicant organizations to understandown product and process consistentlyWe do NOT feel necessity for majorchange of current Japanese is main Document forQOS is main Document forReviewing NDA in JapanReviewing NDA in Japan Expert team in PMDA reviews NDA using module 2(QOS) as main review document and referring tomodule 3, and prepares a review report. (Final)QOS and review report are submitted to theCommittees on new drugs in the PharmaceuticalAffairs and Food Sanitation Council (PAFSC). The committee members discuss Quality , efficacyand safety of the drug based on the review reportand QOS. (Usually, the committee members donot review module 3.) The opinion of the committee is sent to MHLW together with the review report, then the Ministerof Health, Labor and Welfare grants the new drugapproval to the Sant Canada CanadaHealth Products and Food BranchDirection g n rale des produits de sant et des alimentsUtilization of theQuality Overall Summary Health Canada PerspectiveSultan GhaniDirectorBureau of Pharmaceutical SciencesTherapeutic Products Directorate (TPD)