data collection tool Oct. 2011 A. National Regulatory System RS01: Legal framework for establishment of a regulatory system, mandate and enforcement power for each function RS01.01: Legislation or and regulation defines the medicinal products for human use to be regulated RS01.02: Legislation or and regulation defines the institutions involved in the vaccine regulatory system, their mandate, functions, roles, responsibilities and enforcement power RS01.03: A policy to establish and implement a Good Regulatory Practices (GRP) RS02: Independence of the regulatory authority in decision making RS02.01: Independence of NRA from researchers, manufacturers, distributors and wholesalers RS02.02: Independence of NRA from procurement system / institutions Tuesday, May 06, 2014 Page 1 of 43
data collection tool Oct. 2011 A. National Regulatory System RS02: Independence of the regulatory authority in decision making RS02.03: Mechanism to manage conflicts of interest RS03: Recall system with mechanism to ensure proper disposition/disposal of affected lots RS03.01: Legal basis or and relevant regulations for NRA to take actions on recall, suspension, withdrawal and/or destruction exists RS03.02: System based on documented communication to appropriate level of the distribution system with feedback mechanism RS03.03: System based on documented confirmation that appropriate, batch traceable, action and/or destruction when necessary has been taken RS04: Total quality management system for all the relevant regulatory functions Tuesday, May 06, 2014 Page 2 of 43
data collection tool Oct. 2011 A. National Regulatory System RS04: Total quality management system for all the relevant regulatory functions RS04.01: Commitment, policy statement and development plan to implement a quality management system relevant to all regulatory functions. RS04.02: Financial support to implement a quality management system RS04.03: Human resources designated and assigned to implement a quality management system RS05: Transparency and public accountability RS05.01: Legal basis and system for transparency and dissemination of information to the public and relevant stakeholders RS05.02: Information related to legislation and regulations is publicly available. Tuesday, May 06, 2014 Page 3 of 43
data collection tool Oct. 2011 A. National Regulatory System RS05: Transparency and public accountability RS05.03: Information on decisions is accessible to the public RS05.04: Information on marketed products and authorized companies is publicly available RS05.05: Information on license withdrawal, sanctions, recalls and public health warnings is publicly available RS05.06: All publicly available information is kept up-to-date RS05.07: Appropriate mechanism for management of confidential information and or proprietary material exists RS05.08: Code of conduct including management of conflicts of interest is published and enforced Tuesday, May 06, 2014 Page 4 of 43
data collection tool Oct. 2011 A. National Regulatory System RS06: Strategic or and detailed Institutional development plan RS06.01: Plan developed, implemented and regularly updated RS06.02: Performance indicators established and used for monitoring progress to meet strategic plan or and institutional development plan RS06.03: Training plan developed, implemented and updated RS07: Advisory and or experts committees RS07.01.Legal basis or and regulations for the establishment of internal or external experts or and advisory committees Tuesday, May 06, 2014 Page 5 of 43
data collection tool Oct. 2011 Function 1: Marketing Authorization and Licensing Activities MA01: System for marketing authorization and licensing for manufacturing activities MA01.01: Provision for marketing authorization and licensing for manufacturing activities MA01.02: Marketing authorization required for all products for which NRA is being assessed MA01.03: License to manufacture granted on the basis of demonstrated compliance with GMP MA02: Quality Management System for marketing authorization and licensing activities MA02.01: Defined organizational chart and responsibilities to implement the Quality Management System MA02.02: Management system to ensure traceability of actions Tuesday, May 06, 2014 Page 6 of 43
data collection tool Oct. 2011 Function 1: Marketing Authorization and Licensing Activities MA02: Quality Management System for marketing authorization and licensing activities MA02.03: Auditing system documented & implemented MA03: Human resource management MA03.01: Adequate qualified staff (number, education, training, skills and experience) to perform MA activities MA03.02: Staff training plan developed and implemented MA03.03: Monitoring acquired skills and or competencies of the staff after training MA04: Submission of Marketing authorization and manufacturing license applications Tuesday, May 06, 2014 Page 7 of 43
data collection tool Oct. 2011 Function 1: Marketing Authorization and Licensing Activities MA04: Submission of Marketing authorization and manufacturing license applications MA04.01: Administrative instructions available for applicants MA04.02: Requirements on the format and content for submission of marketing authorization applications consistent with global standards available to applicants MA04.03: Requirements on the format and content for submission of manufacturing license applications (including format of the authorization) available to applicants MA05: Assessment of Quality, Safety and Efficacy (Q,S,E) MA05.01: Assessment of product related information (legal part and quality) MA05.02: Assessment of clinical data (safety & efficacy) Tuesday, May 06, 2014 Page 8 of 43
data collection tool Oct. 2011 Function 1: Marketing Authorization and Licensing Activities MA05: Assessment of Quality, Safety and Efficacy (Q,S,E) MA05.03: Assessment report prepared and used as reference for decision MA05.04: Policy with written criteria for recognition of other NRA s reports/decisions (if applicable) MA05.05: Assessment of the manufacturing license application MA06: GMP assessment during marketing authorization process MA06.01: GMP assessment for domestic manufacturers through dedicated inspections on the manufacture site Tuesday, May 06, 2014 Page 9 of 43
data collection tool Oct. 2011 Function 1: Marketing Authorization and Licensing Activities MA06: GMP assessment during marketing authorization process MA06.02:GMP assessment for nondomestic manufacturers a.agreement with other NRA for exchange of inspection reports/gmp certificates or list of reference countries/agencies that certificates and decisions are accepted or b.foreign country Inspection MA07: Requirements for variations to be submitted and assessed MA07.01: Written guidelines for applicants with definition of types and scopes of variations and documentation required MA07.02: Written guidelines for assessment based on type of variation MA08: Clear and comprehensive information on authorized products Tuesday, May 06, 2014 Page 10 of 43
data collection tool Oct. 2011 Function 1: Marketing Authorization and Licensing Activities MA08: Clear and comprehensive information on authorized products MA08.01: NRA approved Summary of Product Characteristics (SPC)-like information available for all products (as basis for lot release) MA08.02: Web site or other official publication with SPC-like information is available and regularly updated MA09: Same criteria/standards for evaluation of marketing authorization applications for products regardless of the source MA09.01: Written criteria to be applied MA09.02: Written criteria to cover circumstances in which the routine licensing procedures may not have to be followed Tuesday, May 06, 2014 Page 11 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV01: Institutional regulations and Guidelines for the monitoring and management of adverse events following immunization (AEFI) PV01.01: Legal provisions for pharmacovigilance exist in the public and or private sectors as appropriate PV01.02: Guidelines exist, are published and accessible, distributed or and available when needed to all staff involved in AEFI surveillance and are actively used PV01.03: Provisions for the NRA to require the marketing authorization holder to perform a specific study of safety in the post-marketing period as necessary PV01.04: Requirements exist for manufacturer to inform NRA of any new safety signal or marketing / regulatory decisions taken in other countries based on safety and is enforced by NRA PV02: Quality Management System for pharmacovigilance activities Tuesday, May 06, 2014 Page 12 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV02: Quality Management System for pharmacovigilance activities PV02.01: Defined Organizational chart & responsibilities to implement the quality management system PV02.02: Management system to ensure traceability of actions PV02.03: Auditing system documented & implemented (external & internal) PV03: Human resource management PV03.01: Adequate qualified staff (number education, training, skills and experience) to perform pharmacovigilance activities PV03.02: Staff training plan developed and implemented Tuesday, May 06, 2014 Page 13 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV03: Human resource management PV03.03: Monitoring of acquired skills and or and competencies of the staff after training PV04: Routine and functional system for regular review of safety and efficacy of the vaccine product for regulatory action PV04.01: AEFI data compiled and analyzed/interpreted on regular (e.g. monthly) basis PV04.02: Information on serious cases and AEFI clusters and investigation reports shared between NRA, NCL, national immunization program, and disease surveillance and pharmacovigilance staff PV04.03: Formal/official communication and regular meetings among above-mentioned key players when dealing with AEFI Tuesday, May 06, 2014 Page 14 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV04: Routine and functional system for regular review of safety and efficacy of the vaccine product for regulatory action PV04.04: Availability of expert committee to review serious AEFI cases and performance of the national PV system PV04.05: Manufacturers are notified of significant safety and efficacy issues and kept up to date or/and at upon request PV04.06: Process to review/assess AEFI and initiate appropriate action including at the sub-national level, when needed PV04.07: Inclusion of zero events in routine periodic reports PV05: Capacity to detect and investigate significant vaccine safety issues Tuesday, May 06, 2014 Page 15 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV05: Capacity to detect and investigate significant vaccine safety issues PV05.01: Demonstrated capacity of the reporting system (active or passive, sentinel or countrywide/statewide) with satisfactory sensitivity PV05.02: Documented evidence of appropriate investigations or sufficient elements indicative of capacity to investigate PV05.03: Evidence of timely reporting and investigations is documented PV05.04: A national database or system for collating, managing and retrieving AEFI reports exists PV06: Regulatory action regarding vaccine performance Tuesday, May 06, 2014 Page 16 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV06: Regulatory action regarding vaccine performance PV06.01: Evidence that appropriate regulatory action consistent with NRA guideline is taken in case of serious AEFI cases PV06.02: NRA regularly informed of data relevant to ongoing assessment of vaccine performance PV07: Communication system is in place to periodically inform stakeholders about AEFI information. PV07.01: Periodic (quarterly or yearly) feedback on AEFI including summary and specific investigation reports PV07.02: Process is established for feedback down to health facility level Tuesday, May 06, 2014 Page 17 of 43
data collection tool Oct. 2011 Function 2: Pharmacovigilance Activities including Surveillance of Adverse Events Following Immunization (AEFI) PV07: Communication system is in place to periodically inform stakeholders about AEFI information. PV07.03: Process is established for feedback to public/community/patients/parents Tuesday, May 06, 2014 Page 18 of 43
data collection tool Oct. 2011 Function 3: NRA Lot release LR01: System for lot release LR01.01: A provision to conduct and enforce lot release exists LR01.02: Lot release is applied to all vaccines LR01.03: Lot release is based as a minimum on summary lot protocol review LR01.04: A mandatory summary lot protocol is part of lot release requirements LR01.05: Acceptance policy or and criteria of lot release performed by another NRA is documented LR01.06: Testing policy for vaccines released Tuesday, May 06, 2014 Page 19 of 43
data collection tool Oct. 2011 Function 3: NRA Lot release LR02: Quality Management System for NRA lot release activities LR02.01: Defined organizational chart and responsibilities to implement the Quality Management System LR02.02: Management system to ensure traceability of actions LR02.03: Auditing system documented & implemented LR03: Human resource management LR03.01: Adequate qualified staff (number, education, training, skills and experience) to perform lot release activities - LR03.02: Staff training plan developed and implemented Tuesday, May 06, 2014 Page 20 of 43
data collection tool Oct. 2011 Function 3: NRA Lot release LR03: Human resource management LR03.03: Monitoring acquired skills and or competencies of the staff after training LR04: Lot release management process LR04.01: Documentation to review summary lot protocol exists LR04.02: Defined acceptance criteria for lot release are documented LR04.03: Lot release records, reports and certificates available LR04.04: Provision for exemption from lot release Tuesday, May 06, 2014 Page 21 of 43
data collection tool Oct. 2011 Function 3: NRA Lot release LR05: Access to product related documentation to guide particular areas of scrutiny in lot release LR05.01: Access to marketing authorization relevant files and updates to NRA staff involved in lot release LR05.02: Access to information related to vaccine quality issues from various existing sources LR06: Monitoring and data analysis for lot release LR06.01: Analysis of lot-to-lot consistency conducted LR06.02: Corrective action taken in case of deviation LR06.03: Regulatory action taken in case of non compliance Tuesday, May 06, 2014 Page 22 of 43
data collection tool Oct. 2011 Function 3: NRA Lot release LR06: Monitoring and data analysis for lot release LR06.04: Follow up and communication with involved parties including the manufacturer on issues of data quality Tuesday, May 06, 2014 Page 23 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA01: System for Quality Control (QC) LA01.01: National Control Laboratory (NCL) established or operational agreement to use external QC laboratory LA01.02: Clearly defined responsibilities for scientific/technical input during the pre and post licensing period - LA01.03: NCL or QC lab involved in definition of specifications and analytical methods during assessment of MA LA02: Quality Management System for laboratory access activities LA02.01: Defined organizational chart and responsibilities to implement the Quality Management System Tuesday, May 06, 2014 Page 24 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA02: Quality Management System for laboratory access activities LA02.02: Written documentation for Laboratory access Quality System exists including guidelines to perform activities - LA02.03: Management system to ensure traceability of actions LA02.04: Auditing system documented & implemented LA03: Human resource management LA03.01: Adequate qualified staff (number, education, training, skills and experience) to perform NCL activities - LA03.02: Staff training plan developed and implemented Tuesday, May 06, 2014 Page 25 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA03: Human resource management LA03.03: Monitoring acquired skills and or competencies of the staff after training LA04: Testing procedures and related documentation LA04.01: Documentation for performing testing activities, handling OOS results and retest policy exists LA04.02: Specifications and validity criteria are defined for all tests LA05: Building and equipment LA05.01: Building and premises are adequate to host National Control Laboratory (NCL) activities Tuesday, May 06, 2014 Page 26 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA05: Building and equipment LA05.02: Documentation relevant to operational manuals, SOPs, log books, records of use, maintenance and calibration of equipment exist and are updated LA05.03: There is a calibration and maintenance plan LA05.04: There are qualifications protocols and reports LA06: Validation policy LA06.01: Validation master plan exist, non-compendial tests have been validated and compendial tests have been verified LA06.02: Procedures for transfers of validated methods is documented (e.g. from manufacturer) Tuesday, May 06, 2014 Page 27 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA07: Risk management for safety LA07.01: The list of hazardous substances is available LA07.02: The responsible staff is designated for the safety program's management LA07.03: There is a procedure for the storage, handling and disposal for hazardous substances LA07.04: Staff immunization requirements are defined, and monitoring of staff immunization records is managed for accessing the required premises or and using equipment LA08: Policy for use of reference standards and reagents LA08.01: System in place to establish and qualify national reference standards (in IU if appropriate) Tuesday, May 06, 2014 Page 28 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA08: Policy for use of reference standards and reagents LA08.02: Appropriate handling and use of reference standards/materials LA08.03: Appropriate handling and use of reagents of assured quality LA08.04: Regular supply system for reference standards/materials LA09: Monitoring, analysis and regulatory outcome of laboratory results LA09.01: Compliance with specifications is systematically checked LA09.02: Corrective action taken in case of deviation Tuesday, May 06, 2014 Page 29 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA09: Monitoring, analysis and regulatory outcome of laboratory results LA09.03: Regulatory action taken in case of non compliance LA09.04: Monitoring and analysis of data trends for laboratory results LA09.05: Monitoring and analysis of data trends for reference standards/materials LA09.06: Comparison of results with those of manufacturer LA10: Participation in international proficiency schemes, collaborative studies and/or interlaboratory comparisons LA10.01: Evidence of regular participation Tuesday, May 06, 2014 Page 30 of 43
data collection tool Oct. 2011 Function 4: Laboratory access LA10: Participation in international proficiency schemes, collaborative studies and/or interlaboratory comparisons LA10.02: Appropriate performance in proficiency schemes, collaborative studies and/or inter-laboratory comparisons Tuesday, May 06, 2014 Page 31 of 43
data collection tool Oct. 2011 Function 5: Regulatory inspections RI01: System for regulatory GMP inspections - RI01.01: National GMP code at least equivalent with WHO GMP (TRS 902[11], TRS 908[16], TRS 822[17] or any update) RI01.02: NRA to ensure that an equivalent system is in place to ensure manufacturer GMP compliance prior to marketing autorization RI01.03: Mandate to inspect and collect samples at any vaccine manufacturing facility in the country RI01.04: Authority to access any premises and documents that are relevant for the inspection RI01.05: Enforcement power to suspend or stop production in any vaccine manufacturing facility in the country Tuesday, May 06, 2014 Page 32 of 43
data collection tool Oct. 2011 Function 5: Regulatory inspections RI01: System for regulatory GMP inspections - RI01.06: Provision or written criteria for recognition of other Inspectorates (NRAs) GMP Certificates, reports and or decisions RI02: Quality Management System for regulatory inspections activities RI02.01: Defined organizational chart and responsibilities to implement the Quality Management System RI02.02: Written documentation for performing activities RI02.03: Management system to ensure traceability of actions RI02.04: 04: Auditing system documented & implemented Tuesday, May 06, 2014 Page 33 of 43
data collection tool Oct. 2011 Function 5: Regulatory inspections RI03: Human resource management - RI03.01: Adequately qualified staff (education, training, skills and experience) to perform inspections and related activities RI03.02: Staff training plan developed and implemented RI03.03: Monitoring acquired skills and or competencies of the staff after training RI04: Procedures for regulatory inspections RI04.01: Documentation for conducting inspections RI04.02: Plan for inspections at appropriate intervals and based on quality risk management exists Tuesday, May 06, 2014 Page 34 of 43
data collection tool Oct. 2011 Function 5: Regulatory inspections RI04: Procedures for regulatory inspections RI04.03: Reports of inspections available for all types of GMP inspections RI04.04: Use of team approach to ensure expertise in specific products RI04.05: Management of conflict of interest and confidentiality provisions is established RI05: Monitoring, analysis and regulatory outcome of inspections RI05.01: Evidence that the follow up process is documented and implemented RI05.02: Evidence that regulatory action is taken in case of non-compliance Tuesday, May 06, 2014 Page 35 of 43
data collection tool Oct. 2011 Function 5: Regulatory inspections RI06: Inspection of distribution channels RI06.01: Provision for monitoring onward distribution as appropriate RI06.02: National GDP code equivalent with WHO GDP (in TRS 937 [18] or any update) and published RI06.03: Only authorized products are distributed RI06.04: Mandate to inspect and to collect samples at any point of the distribution chain of vaccines in the country Tuesday, May 06, 2014 Page 36 of 43
data collection tool Oct. 2011 Function 6: Regulatory oversight of clinical trials CT01: System for regulatory oversight of clinical trials (CTs) CT01.01: Provision for regulation of clinical trials consistent with WHO Good Clinical Practices guideline (GCP) exists CT01.02: Roles and responsibilities of all stakeholders/institutions involved in CTs are defined CT01.03: Mandate and enforcement power for NRA to inspect, suspend or/and stop CT is defined and documented CT01.04: Regulatory authorization for importation-release of investigational products is required CT01.05: GCP inspection system established and implemented CT01.06: AEFIs during CT reported to NRA and/or ethics committee Tuesday, May 06, 2014 Page 37 of 43
data collection tool Oct. 2011 Function 6: Regulatory oversight of clinical trials CT01: System for regulatory oversight of clinical trials (CTs) CT01.07: Feedback report from sponsors or contract research organizations (CROs) during and after clinical trials are available or and send sent to NRAs /ethic Committee CT02: Quality Management System for oversight of clinical trials activities by NRA CT02.01: Defined Organizational chart & responsibilities to implement the quality management system CT02.02: Written documentation for performing activities CT02.03: Management system to insure traceability of actions CT02.04: Auditing system documented & implemented Tuesday, May 06, 2014 Page 38 of 43
data collection tool Oct. 2011 Function 6: Regulatory oversight of clinical trials CT03: Human resource management CT03.01: Adequate qualified staff (number, education, training, skills and experience) to perform CT oversight activities CT03.02: Staff training plan developed and implemented CT03.03: Monitoring acquired skills and or competencies of the staff after training CT04: Format and content for submission of clinical trials application CT04.01: Guidelines on the format, content and process for submission of clinical trial application available to the applicants CT04.02: Documentation for the acceptance of CT applications and records established Tuesday, May 06, 2014 Page 39 of 43
data collection tool Oct. 2011 Function 6: Regulatory oversight of clinical trials CT04: Format and content for submission of clinical trials application CT04.03: Meetings to advise sponsors and/or principal investigators to meet regulatory requirements CT05: Assessment of clinical trials application CT05.01: Investigational pharmaceutical products manufactured in compliance with GMP requirements with appropriate quality data submitted CT05.02: Preclinical data submitted for Investigational Pharmaceutical Products CT05.03: Previous clinical experiences with the Investigational Pharmaceutical Products submitted CT05.04: Assessment of CT protocol and regulatory decision Tuesday, May 06, 2014 Page 40 of 43
data collection tool Oct. 2011 Function 6: Regulatory oversight of clinical trials CT06: Assurance of ethical oversight CT06.01: Defined roles for Ethics Committees (ECs) at all levels CT06.02: EC responsibility for approval and follow-up until completion of clinical trial is defined CT06.03: Appropriate composition of Ethics Committees is defined CT06.04: Functioning and documentation of the management of Ethics Committee CT06.05: Issuance of the approval, decision or recommendation is documented Tuesday, May 06, 2014 Page 41 of 43
data collection tool Oct. 2011 Tuesday, May 06, 2014 Page 42 of 43
data collection tool Oct. 2011 Tuesday, May 06, 2014 Page 43 of 43