DEPARTMENT OF HEALTH Medicines Regulatory Affairs Date DEPARTMENT OF HEALTH Medicines Regulatory Affairs (Pharmaceutical & Related Product Regulation & Management) EDMS Workflow Specification and Software Configuration Project Update E Taute SAPRAA 21 Nov 2008 The EDMS Workflow Specification and Software Configuration Contract is the biggest and core activity for the MRA EDMS project. The MRA EDMS Project consists of 16 activities forming a logical and coherent transition from a paper based business model to an electronic based business model. This is an update of the EDMS Project and more specifically the Workflow Specification and Software Configuration contract.

Date The logical sequence of events for transition is based on 8 major milestones. The workflow and configuration contract forms milestone or step number 4-7 of this sequence. Eleven other activities combine with this contract to give the final end result of an electronic business system. The periferal activities marked in the non-connected boxes impact on the logical steps as marked in each box. The timelines for the steps 4-7 are as follows: (next slide)

EDMS Workflow Specification and Software Configuration Timeline Date EDMS Workflow & Configuration Project EDMS Workflow Specification and Software Configuration Timeline Project Phases (Deliverable) Date Phase 1 – Assessment May 2008 Phase 2 – Design To-Be Environment July 2008 Phase 3 – Configuration November 2008 Phase 4 – Testing February 2009 Phase 5 – Implement/Operate May 2009 The EU Funding requires closure of all the contracts by 31 May 2009 and therefore the timelines are set to be completed by the same date. Thereafter the configuration of all the software follows to simulate the final electronic business model for the MRA. The internal testing and pilot verification will follow the configuration phase to ensure that the electronic model functions adequately and that all operations can be implemented. It is expected that the deployment of the system to industry will be implemented during March, April and May of 2009.

Date EDMS Workflow & Configuration Project It is expected that the EDMS Project will provide the following within the scope of the configuration contract : Conformance to local regulatory requirements Ability to perform search and retrieval operations on the information stored in the system Ability to perform workflow management in-house Provide web-enabled centralised control Conform to international regulatory standards Conform to Government IT standards Provide necessary tools to perform publication of updated information on website Provide ability to maintain security/control via digital signatures Ability to deliver version and iteration control Provide a clear archiving strategy; and Accommodate paper-based submissions The EDMS Project is expected to provide the MRA with major advantages in document and information management such as: High performance search and retrieval Flexibility to change workflow configuration in house Conform to Government and International IT and Regulatory Standards Automated publishing of public domain information High security environment Sophisticated change management and archiving capabilities

Current and Future Commitments Date EDMS Workflow & Configuration Project Current and Future Commitments Workflow Configuration Document Configuration Scanning Capacity Training Information Management Data Management Change Management Human Resource Capacity Building The MRA is therefore entering a new phase in its operational lifespan with a well coordinated and investigated state-of-the-art electronic system. In order to sustain this new system, the MRA is committing to various new operational and support functions such as: - Workflow and document configuration - Organisational and document change management - Extensive training and human resource capacity building - Data and information management leading to total knowledge management

Major Indicators International agency implementation & harmonization Date EDMS Workflow & Configuration Project Major Indicators International agency implementation & harmonization Local Industry acceptance with provisos - security, compatibility, capacity Electronic process will satisfy environmental & archiving concerns Data integration Business Process Management (Standardisation and time-line control) Knowledge Management (Management reporting, supervision and efficiency) Format cross indexing (MBR1  MRF1  eCTD) Capacity building The major indicators for the MRA are centered around: International and especially SADC harmonisation and implementation Local industry cooperation Publication of public domain information Standardised data and information management Flexible data and process integration Capacity building and sustainable environmental protection National archiving

MRA Network Topology Date The MRA EDMS will be supported with a small secure local area network (LAN) as well as a wide area network (WAN) with a web enabled centralised control from the server. This means that all users are registered on the system against a “username” and “password” and can access the system from anywhere through an internet connection. The access rules will conform with the International regulatory requirements of the International Committee on Harmonisation, the USA Federal Drug Administration, the European Medicine Evaluation Agency and the South African Government Standards. The system design also provides for the possible integration of video conferencing and thus recording of audio and video proceedings.

Successes and Milestones Date EDMS Workflow & Configuration Project Delays and Problems EU Funding Delay in award of contract and eventual sign-off Software funded by DoH Specialists for testing (implementation support) – Appointment not approved Data capturers not yet optimally utilised Server security Amendment Bill Successes and Milestones Windchill in Licensing up and running Hardware Audit Completed As-Is Process Maps completed To-be Process Maps completed Commenced with configuration Major change in registration process – GMP approval up front Slide 9 9

EDMS Workflow & Configuration Project CTD / eCTD Why? Harmonisation To provide for a common format/template for the submission of information to the regulatory authorities in the 3 ICH regions + South Africa “Common Technical Document” signed-off by ICH in November 2000 Advantages / Objectives: Resource saving for industry Facilitate simultaneous submission in all the regions Facilitate exchange of regulatory information Harmonised format to be further supported by the eCTD More efficient assessment, e.g. use of hyperlinks Faster availability of new medicines

EDMS Workflow & Configuration Project CTD / eCTD However, CTD is only a FORMAT ! It’s not a “single” dossier, with a “single” content since Legal requirements differ in the regions ICH guidelines have not yet harmonised all requirements SA guidelines not all harmonised Pharmacopoeiae are not harmonised

EDMS Workflow & Configuration Project Module 1: Not Part of the CTD Content to be determined by authorities Module 1 Regional Information 1.0 CTD Table of Contents 2.1 CTD Introduction 2.2 Module 2 Module 2 Module 2 Non-clinical Overview 2.4 Clinical Overview 2.5 Quality Overall Summary 2.3 Module 2-5 CTD Non-clinical Summaries 2.6 Clinical Summary 2.7 Module 3 Quality 3.0 Module 4 Non-clinical Study Reports 4.0 Module 5 Clinical Study Reports 5.0 Modules 3 - 5 12

Heart of Dossier MRF1 PART 2 Basis for Registration and Overview of Application PART 2A Pharmaceutical and biological availability PART 2B SBRA PART 2C Pharmaceutical Expert Report PART2D Pre-Clinical Expert Report PART 2E Clinical Expert Report CTD Module 2 Section 2.3 Quality Overall Summary Section 2.4 Nonclincial Overview Section 2.6 Nonclinical Written and Tabulated Summaries Section 2.5 Clinical Overview Section 2.7 Clinical Summary

Technical “part” of Dossier CTD Module 3 3.2.S Drug substance 3.2.P Drug Product 3.2.P.1 Description and composition of the drug 3.2.S.4 Control of Drug Substance 3.2.P.4 Control of Excipients 3.2.P.7 Container Closure System 3.2.P.3 Manufacture 3.2.P.5 Control of Drug Product 3.2.P.8 Stability 3.2.P.2 Pharmaceutical Development MRF1 PART 3 Pharmaceutical & Analytical PART 3A: Active Pharmaceutical Ingredient (API) PART 3B: Formulation PART 3C: Specifications & Control Procedures for Pharmaceutical Ingredients PART 3D: Container & Packaging Materials PART 3E: Manufacturing Procedure PART 3F: Final product Specifications & Control PART 3G: Stability Data of the Finished Pharmaceutical Product (FPP) PART 3H: Pharmaceutical Development PART 3I: Expertise and premises used for the Manufacture of a Biological Medicine

Technical “part” of Dossier MRF1 PART 3 Pharmaceutical & Analytical PART 3A: Active Pharmaceutical Ingredient (API) PART 3B: Formulation PART 3C: Specifications & Control Procedures for Pharmaceutical Ingredients PART 3D: Container & Packaging Materials PART 3E: Manufacturing Procedure PART 3F: Final product Specifications & Control PART 3G: Stability Data of the Finished Pharmaceutical Product (FPP) PART 3H: Pharmaceutical Development PART 3I: Expertise and premises used for the Manufacture of a Biological Medicine CTD Module 3 3.2.S Drug substance 3.2.S.4 Control of Drug Substance 3.2.P Drug Product 3.2.P.1 Description and composition of the drug 3.2.P.2 Pharmaceutical Development 3.2.P.3 Manufacture 3.2.P.4 Control of Excipients 3.2.P.5 Control of Drug Product 3.2.P.6 Reference Standards or Materials 3.2.P.7 Container Closure System 3.2.P.8 Stability 3.3 References

EDMS Workflow & Configuration Project CTD/eCTD Challenges EU eCTD vs MRF1 vs SA eCTD Module 1 PART1 Screening BE data + dissolution data Reference products Module 3 “Body of Data” On-line submission / CD / DVD Paper submissions Paradigm shift