Risk Management Principles for Devices and Pharmaceuticals
v
SECTION V: REMS. ...............................................................................................................343
Chapter 23 Developing, Implementing, and Operating REMS Programs. ........................................345
Paul Sheehan, MSJ, BSc, Lindsay Crampton, BSc, and Jemma Contreras, PhD, BSc
Figures
Figure 1-1. Overview of Risk Management. ..........................................................................................5
Figure 1-2. Safety Focus Throughout a Product’s Lifestyle. ...................................................................6
Figure 1-3. Comparison of Monitoring and Control for a Traditional Product Launch versus a
Product Launched With a Risk Management Plan.............................................................7
Figure 1-4. US Drug Regulation Advancements..................................................................................19
Figure 1-5. Distribution of Combinations of Risk Management Elements Required by FDA
(based on 2022 Active REMS Elements Combinations)...................................................22
Figure 1-6. Comparison of Combination of Active REMS Elements 2008–10 and 2011...................23
Figure 1-7. Assessment of Effectiveness of REMS Medication Guide................................................25
Figure 1-8. Example of a REMS Assessment Implementation Timeline............................................27
Figure 1-9. FDA Postmarket Commitments and Requirements by Year ........................................29
Figure 1-10. FDA Postmarket Safety Requirements by Type.................................................................30
Figure 1-11. History of the Sentinel Initiative........................................................................................32
Figure 1-12. Overview of the Mini-Sentinel Safety Question Evaluation Process. ...............................33
Figure 2-1. Postapproval Surveillance System. .....................................................................................42
Figure 2-2. Timeline for Postapproval Surveillance System* ...............................................................43
Figure 3-1. Process for Developing a Risk Minimization Plan. ...........................................................54
Figure 3-2. Sample Benefit-Risk Profile Template...............................................................................55
Figure 3-3. Benefit-Risk and Risk Minimization Process. ...................................................................56
Figure 4-1. Risk Management Overview (AS/NZA ISO 31000:2018)...............................................60
Figure 5-1. Risk Management Process. ................................................................................................77
Figure 7-1. Risk Management Process Steps......................................................................................102
Figure 7-2. Risk Management Flow Using Hazard Analysis Technique............................................103
Figure 7-3. ISO 14971 Integration with Regulations and Standards. ................................................111
Figure 7-4. ISO 13485 Activities Related to Risk Management........................................................113
Figure 7-5. Medical Device Use. ........................................................................................................116
Figure 7-6. Relation Between ISO 14971 and IEC 62366-1.............................................................117
Figure 8-1. Failure Mode and Effect Analysis (FMEA) Cycle. .........................................................124
Figure 8-2. Three-Step RPN-based Risk Evaluation. ........................................................................127
Figure 8-3. Example of QRM in Action. ...........................................................................................128
Figure 9-1. Example of FDA Medical Device Classifications............................................................134
Figure 9-2. Seven Risks of Medical Devices.......................................................................................139
Figure 9-3. The Risk Cycle.................................................................................................................141
Figure 9-4. Generic SWEATT Model...............................................................................................143
Figure 9-5. Software Product Design SWEATT Model: Before.......................................................147
Figure 9-6. Software Product Design SWEATT Model: After.........................................................148
Figure 9-7. Product Risk SWEATT Model.......................................................................................150
Figure 10-1. Shifting Safety Focus as Medicines Mature.....................................................................154
Figure 11-1. Clinical Investigation Registration Requirements............................................................175
Figure 12-1. Noninterventional Postauthorization Safety Study Requirements...................................185
Figure 12-2. Endorsement for Single-Country Postauthorization Safety Studies Procedure..............189
Figure 12-3. Module I Requirement Compliance Approach................................................................192
Figure 12-4. Activities Impacting PV System Quality. ........................................................................193
Figure 13-1. Asking the Right Questions. ...........................................................................................206