Postapproval Changes for Drugs: A Practical Guide
v
Figure 9-2. PMDA Postapproval Process and Timelines.................................................................... 106
Figure 15-1. US FDA Postmarket Requirement and Commitment Studies,
January 2017 to December 2021....................................................................................... 180
Figure 15-2. US FDA Postmarket Requirements and Commitments January -December 2020. .......181
Figure 20-1. Signal Detection and Risk Management Diagram. ..........................................................231
Figure 21-1. Handling of Signals Detected by MAHs in EudraVigilance............................................ 240
Tables
Table 3-1. List of Documents Required in the Renewal Application. .................................................19
Table 5-1. Postapproval Regulations in Each MENA Country ..........................................................41
Table 5-2. MAH Class of Change and Approval Time ......................................................................50
Table 6-1. GDUFA Approval Timelines for Prior Approval Supplements (PAS)............................... 63
Table 6-2. USP Guidances Overview................................................................................................... 64
Table 6-3. Brazilian Regulatory Actions Taken in Response to Nitrosamine Impurities ....................66
Table 6-4. Health Canada Actions Taken in Response to Nitrosamine Impurities.............................. 66
Table 6-5. Regulatory Guidance Issued in Chile in Response to Nitrosamine Impurities................... 66
Table 6-6. US Regulatory Actions Taken in Response to Nitrosamine Impurities. .............................67
Table 6-7. Drug Product Complex Change Evaluation Process........................................................... 69
Table 6-8. Impact on Other Countries: Marketing Changes to a Finished Product
Manufacturing Site of a Modified-Release Tablet Dosage Form ......................................70
Table 6-9. Drug Substance/DMF Complex Change Evaluation Process. ...........................................71
Table 6-10. Change to Drug Substance – Other Countries................................................................... 72
Table 7-1. Approval Timeline for EU Variations. ................................................................................79
Table 7-2. Container Closure System Classification Guidelines Example.......................................... 87
Table 8-1. Change of Manufacturing Site (COS) Types in Malaysia. .................................................99
Table 8-2. Data Requirements for Change in Manufacturing Sites (COS) in Malaysia.................... 100
Table 10-1. Americas: Comparison of Regulations Across Jurisdictions .............................................113
Table 10-2. Mexico: Variation Procedures Concerning Product Information. .....................................117
Table 12-1. Overview of Safety and Product Information Changes ...................................................142
Table 12-2. Safety and Drug Information Changes Samples............................................................... 143
Table 13-1. Regulatory Authorities and Original Drug Laws/Regulations ........................................149
Table 13-2. Review and Approval Timelines for Safety Labeling Updates .........................................152
Table 13-3. Overview of a Safety Labeling Submission in GCC Countries........................................ 154
Table 13-4. Overview of a Safety Labeling Submission in North African Countries. .........................155
Table 14-1. NMRAs and Guidelines for Pharmaceuticals in African Countries................................. 161
Table 14-2. Examples of SAHPRA Exceptions to the EU Variation Classification: Safety and
PI-Related Changes.......................................................................................................... 168
Table 15-1. Information Provided in the FDA Postmarketing Commitments Database.................... 179
Table 15-2. Summary of Open and On-Schedule Postmarketing Studies per Applications
Approved 2009–2019 by FDA’s CDER and CBER. ........................................................182
Table 15-3. Information Provided in the Health Canada Notice of Compliance with Conditions
(NOC/c) Database............................................................................................................ 184
Table 15-4. ANMAT 5358/2012 (Annex I): Summary of Phase IV Study Protocols to be
Conducted in Argentina................................................................................................... 187
Table 15-5. Regulatory Framework for Postauthorization Studies in Major America Regions. ..........189
Table 15-6. Comparison of Postmarket Commitments in the US and Canada (ABECMA).............. 191
Table 15-7. Comparison of Postmarket Commitments in the US and Canada (COMIRNATY)...... 192
Table 17-1. Regulations and Guidance Documents ............................................................................204
Table 20-1. Regional Regulatory Authorities ......................................................................................225
v
Figure 9-2. PMDA Postapproval Process and Timelines.................................................................... 106
Figure 15-1. US FDA Postmarket Requirement and Commitment Studies,
January 2017 to December 2021....................................................................................... 180
Figure 15-2. US FDA Postmarket Requirements and Commitments January -December 2020. .......181
Figure 20-1. Signal Detection and Risk Management Diagram. ..........................................................231
Figure 21-1. Handling of Signals Detected by MAHs in EudraVigilance............................................ 240
Tables
Table 3-1. List of Documents Required in the Renewal Application. .................................................19
Table 5-1. Postapproval Regulations in Each MENA Country ..........................................................41
Table 5-2. MAH Class of Change and Approval Time ......................................................................50
Table 6-1. GDUFA Approval Timelines for Prior Approval Supplements (PAS)............................... 63
Table 6-2. USP Guidances Overview................................................................................................... 64
Table 6-3. Brazilian Regulatory Actions Taken in Response to Nitrosamine Impurities ....................66
Table 6-4. Health Canada Actions Taken in Response to Nitrosamine Impurities.............................. 66
Table 6-5. Regulatory Guidance Issued in Chile in Response to Nitrosamine Impurities................... 66
Table 6-6. US Regulatory Actions Taken in Response to Nitrosamine Impurities. .............................67
Table 6-7. Drug Product Complex Change Evaluation Process........................................................... 69
Table 6-8. Impact on Other Countries: Marketing Changes to a Finished Product
Manufacturing Site of a Modified-Release Tablet Dosage Form ......................................70
Table 6-9. Drug Substance/DMF Complex Change Evaluation Process. ...........................................71
Table 6-10. Change to Drug Substance – Other Countries................................................................... 72
Table 7-1. Approval Timeline for EU Variations. ................................................................................79
Table 7-2. Container Closure System Classification Guidelines Example.......................................... 87
Table 8-1. Change of Manufacturing Site (COS) Types in Malaysia. .................................................99
Table 8-2. Data Requirements for Change in Manufacturing Sites (COS) in Malaysia.................... 100
Table 10-1. Americas: Comparison of Regulations Across Jurisdictions .............................................113
Table 10-2. Mexico: Variation Procedures Concerning Product Information. .....................................117
Table 12-1. Overview of Safety and Product Information Changes ...................................................142
Table 12-2. Safety and Drug Information Changes Samples............................................................... 143
Table 13-1. Regulatory Authorities and Original Drug Laws/Regulations ........................................149
Table 13-2. Review and Approval Timelines for Safety Labeling Updates .........................................152
Table 13-3. Overview of a Safety Labeling Submission in GCC Countries........................................ 154
Table 13-4. Overview of a Safety Labeling Submission in North African Countries. .........................155
Table 14-1. NMRAs and Guidelines for Pharmaceuticals in African Countries................................. 161
Table 14-2. Examples of SAHPRA Exceptions to the EU Variation Classification: Safety and
PI-Related Changes.......................................................................................................... 168
Table 15-1. Information Provided in the FDA Postmarketing Commitments Database.................... 179
Table 15-2. Summary of Open and On-Schedule Postmarketing Studies per Applications
Approved 2009–2019 by FDA’s CDER and CBER. ........................................................182
Table 15-3. Information Provided in the Health Canada Notice of Compliance with Conditions
(NOC/c) Database............................................................................................................ 184
Table 15-4. ANMAT 5358/2012 (Annex I): Summary of Phase IV Study Protocols to be
Conducted in Argentina................................................................................................... 187
Table 15-5. Regulatory Framework for Postauthorization Studies in Major America Regions. ..........189
Table 15-6. Comparison of Postmarket Commitments in the US and Canada (ABECMA).............. 191
Table 15-7. Comparison of Postmarket Commitments in the US and Canada (COMIRNATY)...... 192
Table 17-1. Regulations and Guidance Documents ............................................................................204
Table 20-1. Regional Regulatory Authorities ......................................................................................225