Regulatory Affairs Professionals Society xi
Figure 22-2. Representative Schematic of Potential Approaches to Conducting Regional-Specific Studies ...............................................315
Figure 22-3. Clinical Development Strategies Employing Local vs. MRCT Strategies ..............................................................................316
Figure 24-1. Continuous Benefit-Risk Assessment for Defining and Maintaining the Safety Profile of Drugs Through the
Development Lifecycle .........................................................................................................................................................................336
Figure 24-2. BRAT Six-Step Process ..........................................................................................................................................................341
Figure 24-3. EMA Eight-Step PrOACT-URL ..........................................................................................................................................342
Figure 24-4. FDA’s Benefit-Risk Framework for New Drug Review ..........................................................................................................342
Figure 26-1. Outcome of PRIME Eligibility Requests by Therapeutic Area ..............................................................................................364
Figure 26-2. Expedited Pathways in Different Development Stages in China ............................................................................................372
Figure 26-3. Standard Marketing Authorization Application Procedures and Expedited Pathways ...........................................................372
Figure 26-4. General Timeframe of SAKIGAKE .......................................................................................................................................379
Figure 26-5. SAKIGAKE Designation Procedure ......................................................................................................................................379
Figure 26-6. Standard Review, Conditional Early Pathway, Priority Review, and Orphan Drugs in Japan ................................................380
Figure 26-7. Conditional Early Pathway Procedures in Japan .....................................................................................................................380
Figure 27-1. ASEAN CTD .........................................................................................................................................................................414
Figure 28-1. Overview of Different Combination Product Categories ........................................................................................................452
Figure 28-2. Argentinian Regulatory Pathway .............................................................................................................................................461
Figure 32-1. How Good Practices Align with the Product Lifecycle........................................................................................................... 518
Figure 32-2. China Drug Regulatory Legislative System .............................................................................................................................525
Figure 32-3. China Drug Regulatory Landscape .........................................................................................................................................526
Figure 33-1. Recall of Clinical Trial Supplies Process Flow ........................................................................................................................533
Figure 34-1. Possible Decisions During the Signal Evaluation Process .......................................................................................................539
Figure 34-2. Benefit-Risk Management Cycle of the Medicinal Product ...................................................................................................540
Figure 35-1. Example of a Reminder Ad .....................................................................................................................................................553
Figure 35-2. Example of a Reminder-Like Ad for a Drug with a Boxed Warning .....................................................................................553
Figure 35-3. General Timeline View of Presubmission Requirements for Subpart E/H Products ..............................................................554
Figure 35-4. Issuance of Enforcement Action Letters Over Time (1997–2024) .........................................................................................559
Figure 36-1. Factors Influencing Medicinal Product Pricing .......................................................................................................................568
Figure 36-2. Process Map for France ...........................................................................................................................................................570
Figure 36-3. Process Map for Germany .......................................................................................................................................................571
Figure 36-4. Mean Length of Time From EMA Authorization to HTA Decision for Oncology Products ...............................................573
Figure 36-5. Overview of ERP Across Europe (2013) .................................................................................................................................574
Figure 36-6. Types of Cost Containment Policies Adopted by Member States ..........................................................................................575
Figure 36-7. Process Map for England ........................................................................................................................................................578
Figure 36-8. Process Map for Scotland ........................................................................................................................................................579
Figure 36-9. Timeline of US HTA-Like Bodies .........................................................................................................................................583
Figure 36-10. Overview of the Canada Public System Reimbursement Decision Pathway .........................................................................585
Figure 36-11. Map of Australian Government HTA Processes for Market Entry and Reimbursement Processes .....................................590
Figure 36-12. Framework for Pricing Drugs and Devices in Japan ..............................................................................................................592
Figure 36-13. Flow Diagram of HTA in South Korea ................................................................................................................................593
Figure 36-14. Historical MaHTAS Milestones ...........................................................................................................................................593
Tables
Table 1 1. Pharmacology Studies – Overview ..................................................................................................................................................8
Table 1 2. Toxicology Studies – Overview .......................................................................................................................................................8
Table 2-1. Current Members and Observers of the ICH Association ...........................................................................................................20
Table 3-1. ALCOA+ Principles of Good Documentation Practice ...............................................................................................................30
Table 3-2. Final Study Report Items ..............................................................................................................................................................31
Table 4-1. Cardiac Ion Channels Assessed by In Vitro Assay in Chinese Hamster Ovary (CHO) Cells and Human Embryonic
Kidney 293 (HEK293) Cells ..................................................................................................................................................................38
Figure 22-2. Representative Schematic of Potential Approaches to Conducting Regional-Specific Studies ...............................................315
Figure 22-3. Clinical Development Strategies Employing Local vs. MRCT Strategies ..............................................................................316
Figure 24-1. Continuous Benefit-Risk Assessment for Defining and Maintaining the Safety Profile of Drugs Through the
Development Lifecycle .........................................................................................................................................................................336
Figure 24-2. BRAT Six-Step Process ..........................................................................................................................................................341
Figure 24-3. EMA Eight-Step PrOACT-URL ..........................................................................................................................................342
Figure 24-4. FDA’s Benefit-Risk Framework for New Drug Review ..........................................................................................................342
Figure 26-1. Outcome of PRIME Eligibility Requests by Therapeutic Area ..............................................................................................364
Figure 26-2. Expedited Pathways in Different Development Stages in China ............................................................................................372
Figure 26-3. Standard Marketing Authorization Application Procedures and Expedited Pathways ...........................................................372
Figure 26-4. General Timeframe of SAKIGAKE .......................................................................................................................................379
Figure 26-5. SAKIGAKE Designation Procedure ......................................................................................................................................379
Figure 26-6. Standard Review, Conditional Early Pathway, Priority Review, and Orphan Drugs in Japan ................................................380
Figure 26-7. Conditional Early Pathway Procedures in Japan .....................................................................................................................380
Figure 27-1. ASEAN CTD .........................................................................................................................................................................414
Figure 28-1. Overview of Different Combination Product Categories ........................................................................................................452
Figure 28-2. Argentinian Regulatory Pathway .............................................................................................................................................461
Figure 32-1. How Good Practices Align with the Product Lifecycle........................................................................................................... 518
Figure 32-2. China Drug Regulatory Legislative System .............................................................................................................................525
Figure 32-3. China Drug Regulatory Landscape .........................................................................................................................................526
Figure 33-1. Recall of Clinical Trial Supplies Process Flow ........................................................................................................................533
Figure 34-1. Possible Decisions During the Signal Evaluation Process .......................................................................................................539
Figure 34-2. Benefit-Risk Management Cycle of the Medicinal Product ...................................................................................................540
Figure 35-1. Example of a Reminder Ad .....................................................................................................................................................553
Figure 35-2. Example of a Reminder-Like Ad for a Drug with a Boxed Warning .....................................................................................553
Figure 35-3. General Timeline View of Presubmission Requirements for Subpart E/H Products ..............................................................554
Figure 35-4. Issuance of Enforcement Action Letters Over Time (1997–2024) .........................................................................................559
Figure 36-1. Factors Influencing Medicinal Product Pricing .......................................................................................................................568
Figure 36-2. Process Map for France ...........................................................................................................................................................570
Figure 36-3. Process Map for Germany .......................................................................................................................................................571
Figure 36-4. Mean Length of Time From EMA Authorization to HTA Decision for Oncology Products ...............................................573
Figure 36-5. Overview of ERP Across Europe (2013) .................................................................................................................................574
Figure 36-6. Types of Cost Containment Policies Adopted by Member States ..........................................................................................575
Figure 36-7. Process Map for England ........................................................................................................................................................578
Figure 36-8. Process Map for Scotland ........................................................................................................................................................579
Figure 36-9. Timeline of US HTA-Like Bodies .........................................................................................................................................583
Figure 36-10. Overview of the Canada Public System Reimbursement Decision Pathway .........................................................................585
Figure 36-11. Map of Australian Government HTA Processes for Market Entry and Reimbursement Processes .....................................590
Figure 36-12. Framework for Pricing Drugs and Devices in Japan ..............................................................................................................592
Figure 36-13. Flow Diagram of HTA in South Korea ................................................................................................................................593
Figure 36-14. Historical MaHTAS Milestones ...........................................................................................................................................593
Tables
Table 1 1. Pharmacology Studies – Overview ..................................................................................................................................................8
Table 1 2. Toxicology Studies – Overview .......................................................................................................................................................8
Table 2-1. Current Members and Observers of the ICH Association ...........................................................................................................20
Table 3-1. ALCOA+ Principles of Good Documentation Practice ...............................................................................................................30
Table 3-2. Final Study Report Items ..............................................................................................................................................................31
Table 4-1. Cardiac Ion Channels Assessed by In Vitro Assay in Chinese Hamster Ovary (CHO) Cells and Human Embryonic
Kidney 293 (HEK293) Cells ..................................................................................................................................................................38