DEPARTMENT OF HEALTH Medicines Regulatory Affairs (Pharmaceutical & Related Product Regulation & Management)

1. 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

3. EDMS Workflow & Configuration Project

4. 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

5. 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

6. 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

8. MRA Network Topology

9. 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 Slide 9

10. 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

11. 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

12. 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 Non-clinical Overview 2.4 Clinical Overview 2.5 Module 2 Quality Overall Summary 2.3 Module2-5 CTD Non-clinical Summaries 2.6 Clinical Summary 2.7 Module 3 Quality 3.0 Module 5 Clinical Study Reports 5.0 Module 4 Non-clinical Study Reports 4.0 Modules 3 - 5 12

13. 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 Heart of Dossier

14. 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.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 Technical “part” of Dossier

15. MRF1 PART 3 Pharmaceutical & Analytical PART3A: Active Pharmaceutical Ingredient (API) PART 3B: Formulation PART 3C: Specifications & Control Procedures for Pharmaceutical Ingredients PART3D: Container & Packaging Materials PART3E: Manufacturing Procedure PART3F: Final product Specifications & Control PART 3G: Stability Data of the Finished Pharmaceutical Product (FPP) PART3H: Pharmaceutical Development PART3I: 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 Technical “part” of Dossier

16. 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