xiv Regulatory Affairs Professionals Society (RAPS)
Table 9-1. DART Strategy for Pharmaceuticals and Biologics Depending on Relevant Species.................................................................... 89
Table 9-2. Embryo-fetal Development (EFD) Study Design Parameters for Rodent, Rabbit and Non-human Primate Species. .................89
Table 9-3. Considerations for Design of a Pre- and Post-Natal Development (PPND) Toxicity Study in Rats............................................. 91
Table 9-4. Considerations for the Design of an Enhanced Pre- and Post-Natal Development Toxicity Study in Nonhuman Primates. .......92
Table 9-5. Potential Species for DART Studies (relative percentages used from a 10-year period at a contract testing facility)..................... 93
Table 10-1. Studies Required During the EU Environmental Risk Assessment Process.............................................................................. 104
Table 11-1. Global Regulatory Active Substances Filling Requirements. .....................................................................................................112
Table 11-2. Master File Classifications. ........................................................................................................................................................116
Table 11-3. Type of Fee (Active Substance Manufacturers). .........................................................................................................................118
Table 11-4. Type of Fee (Active Substance Importers and Distributors)....................................................................................................... 118
Table 12-1: Standards and Guideline Types That Apply in Clinical Supply. ................................................................................................126
Table 12-2: Standards and Guideline Types That Apply in Non-Clinical Supply......................................................................................... 126
Table 12-3. Components of Clinical Supply Chain Strategy. .......................................................................................................................127
Table 12-4. Clinical Development Stages. ....................................................................................................................................................127
Table 12-5. FDA Regulations Relating to GCP and Clinical Trials. ............................................................................................................130
Table 12-6. Comparing Clinical and Non-Clinical Material Supply. ...........................................................................................................131
Table 12-7. Factors to Consider When Selecting Excipients. .......................................................................................................................133
Table 13-1. QbD regulatory guidance comparison in major markets............................................................................................................ 144
Table 13-2. Container Content/Volume Label Claim/Extractable Volume Test Regional Comparison....................................................... 146
Table 13-3. Dosage Form Compatibility Cases............................................................................................................................................. 149
Table 13-4. Typical Packaging Suitability Considerations for Common Classes of Drug Products.............................................................. 149
Table 13-5. Modified FDA/CDER/CBER Risk-based Approach to Consideration of Leachables............................................................. 150
Table 13-6. Dissolution Specification Setting Considerations. .....................................................................................................................152
Table 13-7. Biopharmaceutics Classification System (BCS). ........................................................................................................................153
Table 13-8. Considerations for Specific Dosage Forms................................................................................................................................. 153
Table 13-9. Applicability of Different Types of Waivers per Dosage Form................................................................................................... 154
Table 13-10. Most Common Routes of Administration: Advantages and Disadvantages. ...........................................................................155
Table 13-11. Comparison of Regulatory Guidance....................................................................................................................................... 157
Table 15-1. Key documents required for the clinical trial application submission US................................................................................... 169
Table 15-2. Changes to EU Legislation for the Conduct of Clinical Trials 2022 to 2025. ...........................................................................170
Table 15-3. Key documents required for the initial clinical trial application submission in the EU.............................................................. 170
Table 15-4. Data requirement for clinical investigation stage in BRICS, APAC, and MENA countries...................................................... 171
Table 15-5. Comparison of data requirements for marketing application stage per region for BRICS, APAC and MENA countries......... 171
Table 16-1. Phase I–IV Clinical/Regulatory Terminology............................................................................................................................ 178
Table 16-2. APAC Countries and Respective Regulatory Authorities.......................................................................................................... 192
Table 16-3. Middle East/North Africa Countries and Respective Regulatory Authorities........................................................................... 197
Table 16-4. Countries of Africa and Their Respective Regulatory Authorities. ............................................................................................200
Table 16-5. Regulatory History of Iclusig®................................................................................................................................................... 205
Table 16-6. Clinical Studies Included in the Initial NDA. ...........................................................................................................................206
Table 16-7. PACE Study Patient Cohorts.................................................................................................................................................... 207
Table 17-1. US Clinical Trial Participant Cross-Section Distribution by Sex, Race, and Age for Select Therapeutic Areas......................... 218
Table 17-2. Percentage of Pfizer Inc. Studies with Participation at or Above US Census Levels Across Therapy Areas............................... 220
Table 17-3. Pfizer Inc. Race and Ethnicity Diversity Plan Template. ...........................................................................................................222
Table 17-4. Government of Canada Historical GBA Initiatives and Activity Timeline. ..............................................................................224
Table 18-1. Formal Meetings Negotiated Under PDUFA (timelines).......................................................................................................... 233
Table 18-2. Formal Meetings Negotiated Under BsUFA (timelines)............................................................................................................ 234
Table 18-3 CADTH Scientific Advice at a Glance...................................................................................................................................... 236
Table 18-4. CADTH Scientific Advice Process. ...........................................................................................................................................237
Table 18-5. Key Timelines for CADTH Scientific Advice Offerings. ..........................................................................................................237
Table 18-6. Types of Questions for Scientific Advice.................................................................................................................................... 239
Table 18-7. Parallel Scientific Advice Timelines. ..........................................................................................................................................240
Table 18-8. EU National Competent Authorities and Scientific Advice. .....................................................................................................241
Table 18-9. Simultaneous NCA Participating Countries. .............................................................................................................................245
Table 18-10. NICE Advice Timelines.......................................................................................................................................................... 247
Table 18-11. PMDA Categories and Content of Consultations for New Medicinal Products. ....................................................................250
Table 9-1. DART Strategy for Pharmaceuticals and Biologics Depending on Relevant Species.................................................................... 89
Table 9-2. Embryo-fetal Development (EFD) Study Design Parameters for Rodent, Rabbit and Non-human Primate Species. .................89
Table 9-3. Considerations for Design of a Pre- and Post-Natal Development (PPND) Toxicity Study in Rats............................................. 91
Table 9-4. Considerations for the Design of an Enhanced Pre- and Post-Natal Development Toxicity Study in Nonhuman Primates. .......92
Table 9-5. Potential Species for DART Studies (relative percentages used from a 10-year period at a contract testing facility)..................... 93
Table 10-1. Studies Required During the EU Environmental Risk Assessment Process.............................................................................. 104
Table 11-1. Global Regulatory Active Substances Filling Requirements. .....................................................................................................112
Table 11-2. Master File Classifications. ........................................................................................................................................................116
Table 11-3. Type of Fee (Active Substance Manufacturers). .........................................................................................................................118
Table 11-4. Type of Fee (Active Substance Importers and Distributors)....................................................................................................... 118
Table 12-1: Standards and Guideline Types That Apply in Clinical Supply. ................................................................................................126
Table 12-2: Standards and Guideline Types That Apply in Non-Clinical Supply......................................................................................... 126
Table 12-3. Components of Clinical Supply Chain Strategy. .......................................................................................................................127
Table 12-4. Clinical Development Stages. ....................................................................................................................................................127
Table 12-5. FDA Regulations Relating to GCP and Clinical Trials. ............................................................................................................130
Table 12-6. Comparing Clinical and Non-Clinical Material Supply. ...........................................................................................................131
Table 12-7. Factors to Consider When Selecting Excipients. .......................................................................................................................133
Table 13-1. QbD regulatory guidance comparison in major markets............................................................................................................ 144
Table 13-2. Container Content/Volume Label Claim/Extractable Volume Test Regional Comparison....................................................... 146
Table 13-3. Dosage Form Compatibility Cases............................................................................................................................................. 149
Table 13-4. Typical Packaging Suitability Considerations for Common Classes of Drug Products.............................................................. 149
Table 13-5. Modified FDA/CDER/CBER Risk-based Approach to Consideration of Leachables............................................................. 150
Table 13-6. Dissolution Specification Setting Considerations. .....................................................................................................................152
Table 13-7. Biopharmaceutics Classification System (BCS). ........................................................................................................................153
Table 13-8. Considerations for Specific Dosage Forms................................................................................................................................. 153
Table 13-9. Applicability of Different Types of Waivers per Dosage Form................................................................................................... 154
Table 13-10. Most Common Routes of Administration: Advantages and Disadvantages. ...........................................................................155
Table 13-11. Comparison of Regulatory Guidance....................................................................................................................................... 157
Table 15-1. Key documents required for the clinical trial application submission US................................................................................... 169
Table 15-2. Changes to EU Legislation for the Conduct of Clinical Trials 2022 to 2025. ...........................................................................170
Table 15-3. Key documents required for the initial clinical trial application submission in the EU.............................................................. 170
Table 15-4. Data requirement for clinical investigation stage in BRICS, APAC, and MENA countries...................................................... 171
Table 15-5. Comparison of data requirements for marketing application stage per region for BRICS, APAC and MENA countries......... 171
Table 16-1. Phase I–IV Clinical/Regulatory Terminology............................................................................................................................ 178
Table 16-2. APAC Countries and Respective Regulatory Authorities.......................................................................................................... 192
Table 16-3. Middle East/North Africa Countries and Respective Regulatory Authorities........................................................................... 197
Table 16-4. Countries of Africa and Their Respective Regulatory Authorities. ............................................................................................200
Table 16-5. Regulatory History of Iclusig®................................................................................................................................................... 205
Table 16-6. Clinical Studies Included in the Initial NDA. ...........................................................................................................................206
Table 16-7. PACE Study Patient Cohorts.................................................................................................................................................... 207
Table 17-1. US Clinical Trial Participant Cross-Section Distribution by Sex, Race, and Age for Select Therapeutic Areas......................... 218
Table 17-2. Percentage of Pfizer Inc. Studies with Participation at or Above US Census Levels Across Therapy Areas............................... 220
Table 17-3. Pfizer Inc. Race and Ethnicity Diversity Plan Template. ...........................................................................................................222
Table 17-4. Government of Canada Historical GBA Initiatives and Activity Timeline. ..............................................................................224
Table 18-1. Formal Meetings Negotiated Under PDUFA (timelines).......................................................................................................... 233
Table 18-2. Formal Meetings Negotiated Under BsUFA (timelines)............................................................................................................ 234
Table 18-3 CADTH Scientific Advice at a Glance...................................................................................................................................... 236
Table 18-4. CADTH Scientific Advice Process. ...........................................................................................................................................237
Table 18-5. Key Timelines for CADTH Scientific Advice Offerings. ..........................................................................................................237
Table 18-6. Types of Questions for Scientific Advice.................................................................................................................................... 239
Table 18-7. Parallel Scientific Advice Timelines. ..........................................................................................................................................240
Table 18-8. EU National Competent Authorities and Scientific Advice. .....................................................................................................241
Table 18-9. Simultaneous NCA Participating Countries. .............................................................................................................................245
Table 18-10. NICE Advice Timelines.......................................................................................................................................................... 247
Table 18-11. PMDA Categories and Content of Consultations for New Medicinal Products. ....................................................................250