Medical device QMS/GMP system and audit

1 Medical device QMS/GMP system and audit Kenichi IshibashiPharmaceuticals and Medical devices AgencyOffice of GMP/QMS InspectionMember GHTFSG3 Overviewof presentationQMS requirementsEstablishment of QMS ISO Documents GHTF SG3 OrdinanceISO13485:200321 CFRPart 820 QMSinspectionPMDANBFDAQMS OrdinanceMinisterial Ordinance on Standards for Manufacturing Control and Quality Control for Medical devices and In-vitro Diagnostics (MHLW Ministerial Ordinance , 2004)ISO13485:2003 Quality Management system Management Responsibility Product Realization Measurement, Analysis and ImprovementQMS Ordinance Seihin Hyojun Sho Paragraph 2 of Article 6 Regulation of Biological-origin Medical device , etc. Manufacturers(Article 73 to 79)Comparison of QMS Ordinance with ISO13485 harmonized to ISO13485: 2003 SeihinHyojunSho(Product Standard Code)The manufacturer shall establish and maintain the document defining the product specifications and QMS requirements (Seihin Hyojun Sho), or identifying Seihin Hyojun Sho.

2 (QMS Ordinance Article 6 Para 2)Quality policyQuality manualSOPsOther documents and recordsSeihinHyojunShoQMS Ordinance requires that the manufacturer shall establish and maintain the document defining the product specifications and QMS requirements (SeihinHyojunSho), or identifying SeihinHyojunSho. (QMS Ordinance Article 6 Para 2) SeihinHyojunShocan be substituted by ISO documents if the relationship between SeihinHyojunShoand ISO documents is clearly ISO DocumentsQMS ordinanceMHLW Notifications NotificationsMay 30th, 2011 Administrative Notice The relationship of QMS ordinance and ISO13485:2003 September 9th, 2005 Administrative Notice Tentative translation of QMS ordinance March 30th, 2005 Notification No. 033001 guidance document of QMS ordinance requirementsOverviewof presentationQMS requirementsEstablishment of QMS ISO Documents GHTF SG3 OrdinanceISO13485:200321 CFRPart 820 QMSinspectionPMDANBFDARole of GHTF SG3 SG3 is responsible for the task of examining existing quality system requirements in countries having developed device regulatory systems and identifying areas suitable for harmonization.

3 SG3 DocumentsTitleDescriptionSG3/N15R8/2005 Implementation of Risk Management Principles and Activities Within a Quality Management system SG3/N99-10 (Edition 2)Quality Management Systems -Process Validation GuidanceSG3/N17/2008 Quality Management system - Medical devices -Guidance on the Control of Products and Services Obtained from Suppliers SG3/N18/2010 Quality Management system - Medical devices -Guidance on corrective action and preventive action and related QMS SG3 DocumentsGHTF/SG3/N15: 2005 Implementation of Risk Management Principlesand Activities within a Quality Management SystemGHTF/SG3/N15: 2005 This document discusses and supports the implementation and integration of a risk management system within a Medical device manufacturer s quality management system and provides practical explanations and Management Activities in Design and DevelopmentGHTF SG3 DocumentsGHTF/SG3/N99-10(Edition 2) Quality Management Systems -Process Validation Guidance A Is Process Output Verifiable B Is Verification Sufficient & Cost Effective No No E Redesign Product and/or Process D Validate Yes Yes C Verify & Control the Process GHTF/SG3/N99-10 This process validation guidanceis intended to assist manufacturers in understanding quality management system requirements concerning process validation and has general applicability to manufacturing (including servicing and installation) processes for Medical devices .

4 The guidance provides general suggestions on waysmanufacturers may prepare forand carry out process validation decision treeGHTF SG3 DocumentsGHTF/SG3/N17:2008 Quality Management system Medical devices Guidance on the Control of Products and Services Obtained from SuppliersThe purpose of N17 is to provide good guidance and examples on the type and extent of control a device manufacturer could impose on its suppliers of a part or service. Guidance provided in the context of an effective ISO 13485:2003 quality management systemDescribewhat is to be obtained (1)Identify potential suppliers(s) (3)Identify controls (5)EXAMPLES OF OBJECTIVE EVIDENCEI dentify technical and process Information (2)Investigate business capability of supplier(s) Investigate operational capability of supplier(s) (6)PHASESS upplier acceptable ?(11)Corrective Action and Preventive Action process (22)(Re-evaluation of supplier) Selection of Potential Supplier(s) Supplier Evaluation and Finalization of Controls Delivery, Measurement, and MonitoringIdentify risk(s) (4)(1) Identification of product and services(2) Specifications, part requirements, procedures, work instructions(3) Name and contact information of potential suppliers(4) Documented list of the risks identified(5) Documented process/product controls for manufacturer and supplier (1) Identification of product and services(2) Specifications, part requirements, procedures, work instructions(3) Name and contact information of potential suppliers(4) Documented list of the risks identified(5) Documented process/product controls for manufacturer and supplier (6) Technological and operational capabilities, logistics, quality, technical risks(7)

5 Selection criteria for potential suppliers, decision rationale(6) Technological and operational capabilities, logistics, quality, technical risks(7) Selection criteria for potential suppliers, decision rationale(8) Documented evaluation and selection criteria(9) Documented initial agreement(s)(10) Documents and records (11) Documented decision and rationale (8) Documented evaluation and selection criteria(9) Documented initial agreement(s)(10) Documents and records (11) Documented decision and rationale (12) Contracts, purchase orders, etc.(13) Acceptance procedures; purchasing requirements(14) Specifications and requirements(15) Records of review and acceptance(12) Contracts, purchase orders, etc.(13) Acceptance procedures; purchasing requirements(14) Specifications and requirements(15) Records of review and acceptance(16) Receiving records(17) Inspection records(18) Acceptance records(19) Records of results of any analysis of data(20) Records of any corrections(16) Receiving records(17) Inspection records(18) Acceptance records(19) Records of results of any analysis of data(20) Records of any corrections(22) Documentation and records of corrective and preventive action process (22) Documentation and records of corrective and preventive action process Feedback & CommunicationFeedback and communication (21)Establish: Purchasing Information (12) Controls (Acceptance Activities, Verifications, etc.)

6 (13, 14, 15)Select potential supplier(s) (7)Additional action required?NoYes Communicate with potential supplier(s) (9)Planning for evaluation and selection criteria (8)Evaluate supplier(s) ability to fulfill specified requirements (10)NoSingle source and/orprocess improvement?NoYesConduct correction (20)(21) Manufacturer and/or supplier correspondence(21) Manufacturer and/or supplier correspondenceProblems identifiedPeriodic re-evaluation of supplier* This box delineates activities that can identify problems with the supplied product/services as well as supplier problems associated with adherence to the supplier arrangements.*Product realization & related processes(16, 17, 18, 19)Receive product/serviceConduct measurement and monitoringAnalyze dataCarry out acceptance activitiesNote: The depicted activities in this figure are not meant to be strictly sequential. In certain cases they may also occur in parallel.

7 GHTF/SG3/N17:2008 GHTF SG3 DocumentsGHTF/SG3/N18:2010 Quality management system Medical devices Guidance on corrective action and preventive action and related QMS processesProvides guidance for establishing adequate processes for measurement, analysis and improvement within the Quality Management system (QMS) as related to correction and/or corrective action for nonconformities or preventive action for potential nonconformities of systems, processes or Measure and Analysecoordination / linkage of data / data sources / horizontal analysis Phase IIMeasurement and Analysis within and across Data Phase Phase Plan for Measurement, Analysis and Improvement Phase IVInput to Report to Management and Management ReviewExamples of defined Data SourcesWithin each data Establish Data Sources and CriteriaFeedbackComplaintsService ReportsSpare parts usageQuality Audits(internal / external)Supplier Performance/ControlsProcess ControlsReturned ProductMarket / customer survey Identify Root Identify Verify identified Implement Determine Effectiveness of Implemented Actions Processes for measurement, analysis and improvementGHTF/SG3/N18:2010 Overviewof presentationQMS requirementsEstablishment of QMS ISO Documents GHTF SG3 OrdinanceISO13485:200321 CFRPart 820 QMSinspectionPMDANBFDAT ypes of QMS InspectionsCompliance inspection1 Pre-approval inspection 2 Post-approval inspection(periodic inspection) For cause inspectionetc.

8 Compliance inspectionsPre-approval Inspection Post-approval inspection Based on application One of the requirements for marketing approval of Medical device Based on application Conducted every five years after marketing authorization Authority of Compliance Inspection Domestic establishmentForeign establishmentIVDNew drugPMDAPMDAR adioactive drugPMDAPMDAO thersPrefectures(CB*for IVDs with certification standards)PMDA(CB for IVDs with certification standards) Medical deviceNew devicePMDAPMDACell/tissue derived devicePMDAPMDAC lass IVPMDAPMDAC lass IIIP refecturesPMDAC lass IIPrefectures(CB*for Medical devices with certification standards)PMDA(CB for Medical devices with certification standards)Class I--CB: Certification body registered by Ministry of Health, Labour and WelfareCompliance Inspections by PMDAT arget products Medical devices and IVDs)1 New Medical devices , new IVDs2 Cell-tissue-derived Medical devices3 Class IV Medical devices4 Radioactive IVDs5 Medical devices manufactured in foreign manufacturing sites(Mainly Class III, IV On-site Inspection and O -site InspectionOn-site inspection is conducted in order ofpriority based on: 1complexity of manufacturing processes; 2risk associated with the use of products; 3results of the previous on-site inspections; and 4previous nonconformity, recall, or the contents ex.

9 New Medical devices , cell-tissue-derived Medical devices , class IV Medical devices 1In principle, two inspectors must be involved 2In principle, for about three days 3 Notify 3-6 weeks before the date of inspection 4 Request for data 1-2 weeks before the date of inspection 5 Inspection in order of priority On-site Inspection QMS inspection schedule (example)DateTime AM Opening meeting GreetingConfirmation on the audit schedule Opening of the audit (declaration) Presentation about the company (Corporate, CRM, plant)Presentation about the plant (Overview, Infrastructure, Main Equipments) Presentation about the product Overview of Quality Management system Quality Manual QMSO rganizationDocument Structure Agreement with MAH Management Responsibility Quality Policy and Quality Objective Management ReviewPM Plant tour AM Design control (incl. Risk Management)Product Information Control-Seihin Hyojunsho Manufacturing Including incoming inspection relating to keycomponents (capacitor, etc.)

10 Product and Process Control Validation Product Identification and Traceability Control of Monitoring and Measuring DevicesPM Control of Nonconforming Product Training10 Purchasing Control (Control of Suppliers and Materials) AM11 Internal Audit12 CAPA Reacall and Adverse EventPM13 PMDA wrap-up 14 Confirmation on findings (Site Quality Director)15 Closing meeting (Site management representative) Timeframe and items are subject to change depending on ..PMDA Website