Guide to EU and UK pharmaceutical regulatory law:
Gespeichert in:
| Weitere Verfasser: | |
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| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Alphen aan den Rijn
Wolters Kluwer
[2023]
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| Ausgabe: | Eighth edition |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | All previous editions were published under the title: Guide to EU pharmaceutical regulatory law |
| Beschreibung: | lxv, 852 Seiten 25 cm |
| ISBN: | 9789403530253 9403530251 |
Internformat
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Datensatz im Suchindex
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Summary of Contents About the Editor and Authors v List of Abbreviations Iv Preface bd Chapter 1 Brexit Sally Shorthose 1 Chapter 2 Overview of European Pharmaceutical Regulatory Requirements Sally Shorthose 11 Chapters Overview of Intellectual Property Rights Sally Shorthose, Marta Sznajder Jonathan Edwards 41 Chapter 4 Clinical Trials Sally Shorthose, Pieter Erasmus, Hester Borgers, Edzard Boonen Anna Koster 79 Chapters Obtaining a Marketing Authorisation Sally Shorthose, Sarah Faircliffe Phillipus Putter 147 Chapter 6 Conditional Marketing Authorisations Sally Shorthose Jonathan Edwards 183 xxi
Summary of Contents Chapter 7 Supplementary Protection Certificates Marta Sznajder Jonathan Edwards 201 Chapter 8 Paediatrics Sally Shorthose, Sarah Faircliffe Pieter Erasmus 247 Chapter 9 Advertising Medicinal Products for Human Use Hester Borgers Edzard Boonen (main chapter, the Netherlands); Marc Martens Benedicte Mourisse (Belgium); Alexandre Vuchot, Johanna Harelimana Nour Saab (France); Christian Lindenthal Wolfgang Ernst (Germany); Mauro Turrini (Italy); Coral Ydnez Ana Maria Sdnchez-Valdepefias Ldpez (Spain); Gabriel Lidman Gunnar Hjalt (Sweden); and Sally Shorthose, Sarah Faircliffe Pieter Erasmus (United Kingdom) 279 Chapter 10 Pharmacovigilance Sally Shorthose, Alexandre Vuchot, Pieter Erasmus, Johanna Harelimana Nour Saab 363 Chapter 11 Variations to Marketing Authorisations Alexandre Vuchot, Johanna Harelimana, Nour Saab Phillipas Putter 421 Chapter 12 Combination Products Sarah Faircliffe 447 Chapter 13 Abridged Procedure Pieter Erasmus 461 Chapter 14 Orphan Medicinal Products Sarah Faircliffe Pieter Erasmus 491 Chapter 15 Biopharmaceuticals Marc Martens, Benedicte Mourisse Sophie Vo 535 xxii
Summary of Contents Chapter 16 Homeopathic, Herbal, and Traditional Herbal Medicinal Products and Cannabis-Based Medicinal Products Pieter Erasmus 559 Chapter 17 Advanced Therapy Medicinal Products Marc Martens, Benedicte Mourisse Sophie Vo 585 Chapter 18 Vaccines Marc Martens Phillipas Putter 603 Chapter 19 Medical Devices Kevin Munungu Sophie Vo 631 Chapter 20 Parallel Trade Christian Lindenthal, Pieter Erasmus Jonathan Edwards 657 Chapter 21 Competition Law in the Pharmaceutical Sector Morten Nissen, Peter Willis Alexander Brochner 685 Chapter 22 Pandemics and Epidemics Hester Borgers, Fenna Douwenga, Edzard Boonen Phillipus Putter 729 Chapter 23 Data Protection in the Pharmaceutical Sector Clara Clark. Nevola Emma Drake 745 Appendix Guidelines and Publications 789 Table of Cases 803 EU Directives 823 Other Legislation 829 EU Regulations 835 Index 839 xxiii
Table of Contents About the Editor and Authors v List of Abbreviations Iv Preface Ixi Chapter 1 Brexit Sally Shorthose §1 .01 Introduction [A] Legislation [B] Medicinal Products and the TCA [C] Research [D] Clinical Trials [E] Marketing Authorisations [F] Quality Assurance and Product Safety [G] Pharmacovigilance [H] Regulatory Authorities [I] Parallel Importation §1 .02 Specific Impacts on IPR [A] Unitary Patent System [B] SPCs [C] Trademarks and Registered Community Designs Chapter 2 Overview of European Pharmaceutical Regulatory Requirements Sally Shorthose §2.01 Introduction [A] History of Pharmaceutical Regulation [B] The European Union XXV 1 1 2 2 3 4 4 5 6 6 6 7 7 7 8 11 11 11 13
Table of Contents §2.02 §2.03 §2.04 [C] Major EU Pharmaceutical Legislation [D] Key EU Pharmaceutical Reform Legislation [E] National Law and Interface with EU Directives Definitions [A] Medicinal Product [B] Generic Medicinal Products [C] Paediatric Medicines [D] Orphan Drugs [E] Biotechnology-Derived Medicinal Products [F] Homeopathic Medicinal Products [G] Herbal Medicinal Products [H] Traditional Herbal Medicinal Products [I] Radiopharmaceuticals [J] Non-prescription Medicines [K] Immunological Medicinal Products [L] In-vitro Diagnostic Devices [Μ] Medical Devices The Regulatory Agencies [A] The European Commission [1] DG Health and Consumers (Commonly Known as ‘SANTE’) [2] The EMA [B] Committees of the EMA [1] CHMP [2] CVMP [3] COMP [4] HMPC [5] PDCO [6] CAT [7] PRAC [C] The Heads of Medicines Agencies [D] NCAs of European Member States [E] CMDh [F] European Directorate for the Qualityof Medicines [G] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Applicable EU Legislation, Including Regulations and Guidance [A] EU Treaties [B] Directives [C] Regulations xxvi 14; 15' 15 16 ■ 16 16 16 17: 18 ' 18 18 ■ 19 j 20 ■ 20 21 21 ; 22 : 23 23 23 i 25 ; 26i 26 ! 28 28 i 29 ; 29 j 30 : 31 ; 32■ 32; 33 34; j 34 35 35j 36i 36
Table of Contents §2.05 [D] The Official Journal of the European Communities [E] Guidelines Guidelines/Publications 37 37 39 Chapter 3 Overview of Intellectual Property Rights Sally Shorthose, Marta Sznajder Jonathan Edwards §3.01 Introduction [A] The Importance of IPRs [B] Ownership §3.02 Patents [A] European Patents [1] Patentability and Scope of Protection [a] Requirements [b] Novelty and Inventive Step [c] Scope of Protection [2] Prosecution and Enforcement [a] EPO Opposition Proceedings [b] National Courts [3] Duration [B] Specific Issues Relating to PharmaceuticalPatents [1] Product by Process [2] Products Obtained Directly by a Patented Process [3] New Chemical Entities (NCEs) [4] Composition and Formulation Claims [5] Methods of Treatment [6] Medical Use [7] Biotechnological Inventions [C] Infringement and Defences [1] Bolar Exemption [2] Experimental Use Defence [D] Unitary Patent System [1] The Legislative Framework [a] Legislative Instruments [b] Ratification [2] Unitary Patent [3] UPC [4] Practical Considerations [a] Cost [b] Divisional Applications [c] Opting Out [d] Licences and Technology Transfer Agreements §3.03 SPCs §3.04 Trademarks xxvii 41 41 42 43 43 44 45 45 46 47 48 48 49 49 50 50 50 51 51 51 52 54 56 56 57 57 59 59 60 60 61 62 62 62 62 62 63 63
Table of Contents Registration of Trademarks [1] Routes to Registration [2] Criteria for Registration [a] Absolute Grounds [b] Relative Grounds [3] Duration [B] Regulatory Issues with Pharmaceutical Names [1] International Nonproprietary Names [2] Public Health Concerns andPatientSafety [a] Purely National, Mutual Recognition and Decentralised Procedures [b] Centralised Procedure [C] Trademark Infringement (1] Criteria for Establishing Infringement [2] Parallel Imports §3.05 Copyright, Database Rights, Design Rights [A] Copyright [B] Database Rights [C] Design Rights §3 .06 Confidential Information [A] Chapter 4 Clinical Trials Sally Shorthose, Pieter Erasmus, Hester Borgers, Edzard Boonen Anna Koster §4 .01 Introduction §4 .02 Regulation (EU) No. 536/2014: CTR [A] Introduction to the CTR [B] When the CTR Applies [C] Implementation of the CTR [D] Aims of the CTR §4.03 Authorisation Procedure for a Clinical Trial [A] Introduction to the Authorisation of aClinical Trial [B] CTIS [C] Authorisation Procedure for a Clinical Trial [D] Ethical Committee Approval [1] Introduction [2] Ethical Committee ApprovalProcess [E] Informed Consent §4 .04 The Substantial Modification of a Clinical Trial §4 .05 Start, End, Halt, and Early Termination [A] Start [B] End [C] Halt [D] Early Termination xxviii 64 64 65 65 66 67 68 68 70 70 71 72 72 74 74 74 74 75 76 79 79 81 81 81 82 82 83 83 84 85 90 90 91 93 96 97 98 98 99 100
Table of Contents §4.06 §4.07 §4.08 §4.09 §4.10 §4.11 §4.12 §4.13 §4.14 §4.15 Conduct of the Clinical Trial [A] Introduction to the Conduct of Clinical Trials [BJ GCP Standards [C] Good Manufacturing Practice Clinical Trial Oversight/Role of the sponsor and Investigator [A] Introduction to Clinical Trial Oversight [B] Monitoring [C] GCP Inspection [D] Sponsor and Investigator as the Same Entity [E] Pharmacovigilance Trial Data [A] Introduction to Trial Data [B] Public Access to Trial Data [C] The Trial Master File: Essential Documents [D] Archiving of the Trial Master File [E] Collection of Data [F] Protection of Data and Storage Requirements FIM Studies Following the TGN1412 Case (TeGenero’) [A] Background [B] Revised CHMP Guidelines as a Result of the TeGenero Case Clinical Trials and Patent Legislation: The Bolar and Research Exceptions Introduction to Clinical Trials in the UK [A] Introduction [B] When the UK Regulations Apply [C] Consultation for Legislative Change (2022) Preparing to Apply for CTIMP Authorisation in the UK [A] Introduction [B] The Sponsor and Overview of Sponsor Duties [1] The Sponsor [2] Overview of Sponsor Duties [C] The Investigator, Chief Investigator, and Principal Investigator [D] Registration and Preparing the CTIMP Authorisation Application [E] Requests for MHRA Scientific Advice Approval to Commence a CTIMP in the UK [A] Introduction to the CTIMP Authorisation Process in the UK [B] MHRA CTIMP Authorisation [C] REC Approval [D] HRA Approval Conduct of CTIMPs in the UK UK CTIMP Oversight [A] Introduction to CTIMP Oversight [BJ Monitoring xxix
100 100 101 103 104 104 105 107 108 109 112 112 112 113 114 114 116 118 118 120 121 122 122 122 123 125 125 125 125 125 127 127 129 130 130 130 131 133 133 134 134 134
Table of Contents §4.16 §4.17 §4.18 [C] MHRA GCP Inspections [D] Internal Audit [E] Urgent Safety Measures [F] Pharmacovigilance Amendments, Suspension, and Termination of CTIMPs in the UK [A] Introduction [B] Amendments by the REC or the MHRA [C] Substantial Amendments by the Sponsor [D] Temporary Suspension of CTIMPs [E] Early Termination of CTIMPs [F] End of CTIMPs [G] CTIMP Summary Results CTIMP Data in the UK [A] Introduction [B] Dissemination of CTIMP Results [C] Storage of Trial Master File [D] Access to NHS Electronic Health Records Guidelines/Publications Chapter 5 Obtaining a Marketing Authorisation Sally Shorthose, Sarah Faircliffe Phillipas Putter §5.01 Approval of Medicines for Human Use: Securing a Marketing Authorisation [A] Introduction and Overview of the Processes [B] Goals of the Approval Process: Demonstration of Quality, Safety, and Efficacy [C] Legislative Background [D] Overview of the Application Dossier [E] Overview of the MA Procedures §5.02 Requirements of the Application Dossier [A] Required Contents of an Application Dossier [1] Manufacturing Authorisations [2] Assurance of Quality of All Constituents [3] New Active Substances [4] Certification of Suitability (CEP) [5] Orphan Drugs [6] Naming the Product [7] Required Product Information [8] SmPC [9] Environmental Risks [10] Pharmacovigilance Systems [11] Submission of Test Results [B] Presentation of the Dossier: CTDoc XXX 135 136 136 137 138 138 138 138 140 140 140 141 141 141 141 143 144 145 147 147 147 148 148 150 150 151 152 153 154 154 155 155 155 156 156 157 157 157 158
Table of Contents §5.03 The CP [A] Scope [В] [C] [1] Optional Scope [2] Mandatory Scope Submission to the EMA Application and Approval Procedure: An Overview [1] [D] [E] [F] [G] §5.04 MRP [A] [B] [C] [D] §5.05 §5.06 §5.07 §5.10 Introduction Application Process Dispute Procedure Timing of the Process DCP [A] Introduction [B] Application Process [C] Dispute Procedure [D] Timing of the Procedure The National Procedure [A] Introduction [B] Application Process Summary and Comparison of the Four Procedures [A] [B] [C] §5.08 §5.09 The CHMP [2] Rapporteur of the CHMP [3] CHMP Assessment [4] Commission Decision [5] Withdrawal [6] Publication Marketing a Medicine Special Procedures [1] Compassionate Use [2] Conditional/Exceptional Circumstances Authorisations Timing of the Process Alternatives to the CP The CP MRP The DCP [D] The National Procedure Continuing Validity, Renewal, and Termination of MAs Obtaining MA in the UK [A] Introduction [B] Overview of the MA Procedures in the UK [C] Summary Guidelines/Publications xxxi 159 159 160 160 161 162 163 163 164 165 165 166 166 167 167 167 168 168 168 168 169 170 171 171 171 172 172 172 173 173 173 173 173 175 175 176 177 178 178 178 180 181
Table of Contents Chapter 6 Conditional Marketing Authorisations Sally Shorthose Jonathan. Edwards §6.01 Introduction §6.02 Criteria for a CMA [A] New MAAs [B] Justification That the Medicinal Product Falls Within the Scope of a CMA [1] Seriously Debilitating Diseases or Life-Threatening Diseases [2] Medicinal Products to Be Used in Emergency Situations [a] Influenza Pandemic [b] Bioterrorism [c] COVID-19 Pandemic [3] Orphan Medicinal Products [C] Requirements for a CMA [1] The Risk/Benefit Balance of the Product Is a Positive [2] It Is Likely That the Applicant Will Be Able to Provide Comprehensive Data [3] Fulfilment of Unmet Medical Needs [4] The Benefits to Public Health of Immediate Availability Outweigh the Risks Inherent in the Fact That Additional Data Are Still Required [D] Specific Obligations [E] Timeframe [F] Amendment to Full MA §6.03 Procedure [A] Prior to Submission of a CMA [B] Timing of the Submission and Documentation to Be Supplied [1] Documents to Be Submitted [a] General Requirements [b] Requirements for the Interim Report on the Specific Obligations [c] CHMP Assessment and Opinion [C] CHMP Assessment of a Request for a CMA [D] Information Included in the Summary of Product Characteristics and Package Leaflet [E] EMA Timetable §6.04 MA Granted in Exceptional Circumstances §6.05 United Kingdom §6.06 Guidelines/Publications xxxii 183 183 184 184 185 185 187 187 187 188 189 190 190 190 191 192 192 193 193 •193 193 193 ' 194 194 195 196 ; 196 197 197 197 198 199
Table of Contents Chapter 7 Supplementary Protection Certificates Marta Sznajder Jonathan Edwards §7.01 Introduction §7.02 The Legislation §7.03 Duration and Scope [A] Duration [1] Basic Term [2] Paediatric Extensions for Medicinal Product SPCs [B] Scope [1] What Is a ‘Product’? [2] The Distinction Between a ‘Product’ and a ‘Medicinal Product’ 209 §7.04 The Procedure for Seeking SPC Protection [A] Time Limit [B] Content of the Application [C] Conditions for Obtaining an SPC [D] Entitlement [E] Third-Party Oppositions and Observations §7.05 Infringement and Invalidation §7.06 Transitional Provisions §7.07 Issues in Relation to SPCs [A] When Is a Product ‘Protected by a Basic Patent in Force’? [1] Construction of Patent Claims (21 Combination Products [3] Amendments to the Basic Patent ' [4] Functional Specifications [5] Multiple SPCs Based upon a Single Patent [B] The Product Has Not Already Been the Subjectof a Certificate [C] First Authorisation to Place the Product on the Market as a Medicinal Product [1] ‘First Authorisation’ (2] Date of First Authorisation [D] What Happens When the Basic Patent and MA Have Different Holders? 231 [E] What Form Can an SPC ‘Claim’ Take and What Effect Does It Have on the Scope of Protection Conferred? §7.08 Legislative Changes and Reforms [A] SPC Manufacturing Waiver [B] The Unitary Patent System and SPCs [1] European SPC [2] Unitary SPCs [a] Grant Authority [b] Scope xxxiii 201 201 202 204 204 204 205 206 207 210 210 211 212 212 213 213 214 217 218 218 219 224 225 226 227 228 228 231 232 233 233 234 235 236 236 236
Table of Contents [C] §7.09 UK [A] [B] [C] [D] [E] [c] Brexit [d] Reform Medical Devices [1] Does the Scope of the SPC Regulation Extend to Medical Devices? [2] European Decisions Concerning Class HI Medical Devices [3] Active Implantable Medical Devices [4] Borderline Products [5] Reform Procedure for Seeking SPC Protection Post-Brexit Duration Paediatric Extensions SPC Manufacturing Waiver CJEU Interpretation 237 237 237 238 239 242 242 243 243 244 245 245 246 246 Chapter 8 Paediatrics Sally Shorthose, Sarah Faircliffe Pieter Erasmus §8.01 §8.02 §8.03 §8.04 §8.05 §8.06 Introduction European Regulations Relating to Paediatric Studies [A] Overview of the EU Paediatric Regulation [B] PDCO [C] PIPs [1] PIP Approval Procedures [2] PIP Compliance Check [3] Issues Concerning PIPs [D] PIP Exemptions, Waivers, and Deferrals [1] Exemptions (2] Waivers [3] Deferrals Rewards for PIP Completion [A] The SPC Extension Reward [1] Zero and Negative-Term SPCs [B] Rewards for Orphan Medicinal Products That Comply with Regulation (EC) No. 1901/2006 [C] Free Scientific Advice from EMA Paediatric Use Marketing Authorisation (PUMA) Post-Approval Obligations [A] Duty to Place Product on Market [B] Pharmacovigilance [C] Product Discontinuation [D] The Paediatric Symbol Penalties xxxiv 247 247 248 248 249 250 252 254 255 257 257 257 258 258 258 260 261 263 263 265 265 265 265 266 266
Table of Contents §8.07 §8.08 §8.09 §8.10 §8.11 Transparency Paediatric Research Developments UK [A] Introduction [B] PIP Submissions [C] PIP Modifications [D] PIP Waivers [E] Compliance Checks [F] Completed Paediatric Studies Guidelines/Publications Chapter 9 Advertising Medicinal Products for Human Use Hester Borgers Edzard Boonen (main chapter, the Netherlands); Marc Martens Benedicte Mourisse (Belgium); Alexandre Vuchot, Johanna Harelimana Nour Saab (France); Christian Lindenthal Wolfgang Ernst (Germany); Mauro Turrini (Italy); Coral Ydnez Ana Maria Sdnchez-Valdepenas Ldpez (Spain); Gabriel Lidman Gunnar Hjalt (Sweden); and Sally Shorthose, Sarah Faircliffe Pieter Erasmus (United Kingdom) §9 .01 Introduction §9 .02 Legislative Basis [A] The General Principles [B] Promotion of OTC Medicines [C] What Is Advertising? [D] Internet Advertising [E] Television Advertising [F] European Case Law on Advertisingof Medicinal Products §9.03 Self-Regulation in Europe [A] Advertising of Prescription-OnlyProducts [1] The EFPIA HCP Code [2] Applicability of the EFPIA Code [3] EFPIA Code and Principles for the Use of Digital Channels [B] Advertising of OTC Products §9.04 Implementation in Belgium [A] Legal Basis [B] Sanctions [C] Role of the National Competent Authority [D] Self-Regulation [E] Cases [F] General Advertising Rules §9.05 Implementation in France [A] Legal Bases XXXV 267 267 269 271 271 272 273 274 274 275 275 279 279 282 282 283 285 285 286 286 289 289 289 290 290 290 291 291 291 291 292 293 293 293 293
Table of Contents §9.06 §9.07 §9.08 [1] Binding Rules [2] Non-binding Rules [В] Scope of Application [C] French Legal Requirements [1] Medicinal Products Advertising [a] Medicinal Products Advertising Directed at Healthcare Professionals [b] Medicinal Products Advertising Directed at the Public 297 [2] Medical Devices Advertising [D] Specific Forms of Advertising [1] Meetings and Congresses [2] Advantages and Gifts [3] Samples of Medicinal Products [E] Sanctions [1] Administrative Sanctions [a] Administrative Authorities [b] Control of Advertising Directed at the Public [c] Control of Advertising Directed at Healthcare Professionals [2] Criminal Sanctions Implementation in Germany [A] Legal Basis [B] Scope of the Advertising of Medicinal Products Act [C] National Sanctions [D] Role of the National Competent Authority [E] National Implementation Beyond Requirements of Directive 2001/83/EC [1] Testimonials [2] Internet Presentations [3] Advertising for Telemedicinal Services [4] Further Requirements [F] Self-regulation Implementation in Italy [A] Legal Basis [B] Scope of the Decree [C] Role of the National Competent Authority [D] Self-Regulation for Promotion of Prescription-Only Products [E] Self-Regulation for Promotion of OTC Products [F] General Advertising Rules [G] Regional Control [H] National Sanctions [I] Online Sales of Medicinal Products on the Internet Implementation in The Netherlands xxxvi 293 294 295 296 296 297 297 298 298 298 300 301 301 301 301 302 302 303 303 303 304 305 305 305 306 307 307 308 308 308 308 309 310 310 310 311 311 311 312
Table of Contents [A] §9.09 Legal Basis [1] The Dutch Medicines Act [a] Enforcement [b] Sanctions [c] Inspections [d] Cooperation with Other Regulating Institutes [В] Civil Law [C] Criminal Law [D] Self-regulation [1] Enforcement [2] Sanctions [3] Code of Conduct Pharmaceutical Advertising [a] Information [b] Comparative Advertising [c] Samples [d] Internet Advertising [4] OTC Advertising Code [5] Inducement [a] Gifts [b] Hospitality [c] Sponsoring and Grants [d] Services [E] Medical Devices [F] Healthcare Products Implementation in Spain [A] Regulatory Aspects [1] Legal Basis [2] The General Principles as Interpreted by Spanish Authorities [3] Advertising Aimed at Persons Qualified to Prescribe or Supply Medicinal Products 325 [a] Advertising Using the Internet [4] Advertising Aimed at the General Public [B] Infringements and Remedies under the Law [C] Self-regulation [1] Spanish Code of Good Practice for the Pharmaceutical Industry [a] Promotion of Medicines and Interaction with Healthcare Professionals 332 [b] Relationships Between the Pharmaceutical Industry and Patient Organisations 334 [2] Spanish Code of Good Practices for the Promotion and Advertising of Non-Prescription Medicinal Products 335 [D] Infringements and Remedies under the Farmaindustria Code xxxvii 312 312 313 313 314 315 315 316 316 316 317 317 318 319 319 319 320 320 321 321 322 322 323 323 324 324 324 325 326 327 328 332 332 335
Table of Contents Implementation in Sweden [A] Legal Basis [B] Scope of the Regulations [C] Role of the MPA: The National Competent Authority [1] Complaints to the MPA [2] Sanctions [D] Self-Regulation [1] The LIF [2] The EthicalRules [3] The IGN andthe NBL [4] The IGN [5] The NBL [6] Agreements on Forms of Collaboration with the Healthcare Sector [7] Other Applicable Rules §9.11 Implementation in the UK [A] Legal Basis [B] Scope of the Regulations [C] Regulation by the MHRA [1] The Blue Guide [2] Advertising Using the Internet [3] Complaints to the MHRA [D] Sanctions [E] Self-Regulation [1] The Association of the British Pharmaceutical Industry (ABPI) and PMCPA [2] PAGB [a] The PAGB Consumer Code [b] The PAGB Professional Code [F] ASA [G] Association of British HealthcareIndustries (ABHI) Annex: Case Histories §9.10 Chapter 10 Pharmacovigilance Sally Shorthose, Alexandre Vuchot, Pieter Erasmus, Johanna Harelimana Nour Saab §10 .01 Introduction and Background §10 .02 Pre-authorisation Pharmacovigilance [A] Legislative Framework [B] First-in-Man Trials [1] Case Study 1 [C] Clinical Trials in Patients [D] The Investigator Brochure xxxviii 336 336 338 338 338 339 339 340 340 341 341 342 343 344 344 344 346 347 347 347 349 350 351 352. 354 355 355 356 357 358 363 363 367 368 370 371 371 372
Table of Contents §10.03 §10.04 §10.05 §10.06 §10.07 §10.08 [E] Reporting SUSARs The Marketing Authorisation Application [AJ Legislative Framework [B] The Requirements Set Out in Directive 2001/83/EC [C] The Reporting of Adverse Reactions [1] Reports to the ΜΑΗ [2] Reports from Patients/Consumers [3] Reports with Name of Active Substance Only [4] Literature Reports [5] Reports from Non-Medical Sources [6] Timescales for Expedited Reporting [7] MedDRA [8] Electronic Reporting [9] Pregnancy Registries [10] Lack of Efficacy [11] Abuse, Misuse, or Overdose [12] Public Health Emergency PSURs [A] Introduction [B] Contents of the PSUR [C] Periodicity of Submission of PSUR [D] PSUR Work-Sharing Initiative The Pharmacovigilance Activities of the Key Parties [A] The EMA [B] Pharmacovigilance Working Party [C] Competent Authorities of the Member States Risk Management and EU-RMP [A] Introduction [B] Content of the EU-RMP [C] Monitoring of the Risk/Benefit Balance and Identification of Safety Signals [D] Risk Management at the MAH's Initiative [E] Risk Management at the EMA’s Initiative [1] Case Study 2: Cerivastatin (Lipobay) Withdrawal [F] Risk Management at National Competent Authorities’ Initiative [1] Case Study 3: Bupropion Compliance with Pharmacovigilance Obligations [A] Legal Basis for Pharmacovigilance Inspections [B] Composition of the Inspection Team [C] Timing of Inspections [D] Conduct of Pharmacovigilance Inspections [E] Common Findings of Inspections [F] Sanctions Summary of Recent Changes xxxix 372 372 373 375 377 377 378 379 379 380 380 381 381 382 382 382 382 383 383
383 384 385 386 386 387 387 390 390 391 392 392 393 394 395 396 396 397 398 399 400 401 403 405
Table of Contents [A] [B] [C] [D] §10.09 §10.10 Pharmacovigilance System Master File Coordination and Inspection: PRAC PASS and PAES Specific Conditions Relating to PhV affecting EMA [1] PSUR Requirements [2] Set-Up of Interconnected Web Portals [3] GVP Guidelines 405 ; 406 ; 408 409 : 409 : 410 1 410 ; 410 i UK [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] Introduction Submission and Receipt of ICSRs Signal Detection Risk Management Plans (RMPs) Periodic Safety Update Reports (PSURs) Post Authorisation Safety Studies (PASS) Safety Referrals Major Safety Reviews Post-authorisation Measures (PAMs) Implementation of Outcomes of EU Referrals and Procedures Concerning PSURs, PASS, Signal Assessments and PAMs [K] Requirements for MAs Granted via the Unfettered Access route [L] Submitting ICSRS [Μ] Provision of Other Pharmacovigilance Data Guidelines/Publications Chapter 11 Variations to Marketing Authorisations Alexandre Vuchot, Johanna Harelimana, Nour Saab Phillipas Putter §11.01 Reason for Variations [A] Changes Not Requiring a Variation [B] Variation Legislation § 11.02 Classification of Changes [A] Types IA and IB [1] Type IA [2] Type IB [3] Re-classification of Type IA and Type IB Variations [B] Type II [1] Definition [2] Type II Categories [3] The International Council on Harmonisation (ICH) Design Space Concept [a] Introduction [b] Process Analytical Technology (PAT) [c] Quality Risk Management [C] Extensions xl 410 : 412 ; 413 413 j 414 i 415 ' 416 : 417 417 418 418 418 418 418 421 421 422 422 423 423 423 425 425 425 425 425 426 426 427 427 427
Table of Contents [1] Changes in Pharmaceutical Form [2] Changes in Strength [D] Classification of Unforeseen Variations §11.03 Substantive Requirements of the Variation Application [A] Variation Applications for Biological Medicinal Products [1] Issues Arising in Relation to Biologicals [2] Regulatory Guidelines [a] Quality Guidelines [b] Safety and Efficacy Requirements §11.04 Variation Application Procedure [A] Forms and Format [B] Grouping of Applications [1] Grouping of Variations Granted under the Mutual Recognition, Decentralised and CentralisedProcedures [2] Grouping of Variations to Purely National MAs [C] Work-Sharing Procedure [D] Products Authorised Through Mutual Recognition [1] Type IA [2] Type IB [3] Type II [E] Centrally Authorised Products [1] Advance Notice [2] Type IA and IB Variations [3] Type II Variations [F] Purely National Procedure [1] Type IA Variations [2] Type IB Variations [3] Type II Variations [G] Urgent Safety Restrictions [H] Human Influenza Vaccines [I] Human Coronavirus Vaccines §11.05 Variations to MAs in the UK [A] Introduction [B] Variation Procedure in the UK [C] Northern Ireland [D] Summary 428 428 429 429 430 430 430 431 431 432 432 433 433 434 434 436 436 437 438 439 439 439 439 441 441 441 441 442 443 443 443 443 444 446 446 Chapter 12 Combination Products Sarah Faircliffe 447 §12.01 Introduction 447 [A] Combination Products 447 [B] Combination Products: Requirement for a MA and Regulatory Data Protection 448 xli
Table of Contents Requirements for Marketing Approval of Fixed-Combination Medicinal Products 450 [A] The Application Dossier 450 [B] The Application Procedure 450 [C] Scientific References, Non-Clinical Tests, and Clinical Trials 451 [D] Necessity for Non-Clinical Tests and Clinical Trials 452 [1] Situations Where Additional Studies Are Necessary 452 [2] Situations Where Fewer Studies Are Necessary 453 [a] Combinations Already in Widespread Use as Free Combination Therapy 453 [b] Combination of Components Already Approved as a Fixed-Combination Product 455 §12.03 Criteria for Approval of Fixed-Combination Products 455 [A] The Risk/Benefit Ratio 455 [B] Relevance of Each Active Substance of the Combination 457 [C] Relevance of the Specific Dosage Regime 457 §12 .04 UK 457 §12 .05 Guidelines/Publications 458 §12.02 Chapter 13 Abridged Procedure Pieter Erasmus §13 .01 Introduction §13 .02 Three Types of Abridged Procedures [A] Abridged Procedure Based on Cross-Reference to Data with Holder’s Consent [B] Abridged Procedure Based on Bibliographic Application for Well-Established Use 464 [1] Well-Established Medicinal Use [2] Ten Years of Use §13.03 Abridged Procedure for Generic Products [A] Data Protection of a Registration File for Six or Ten Years [B] Data Protection and Marketing Exclusivity, 8 + 2 Years [C] Data Protection Rules Applicable Within the EU until 30 October 2015 [D] European Reference Medicinal Product [1] Global MA [2] Reference to Products Authorised in the Member States: Cyprus, Lithuania, Malta, Poland, andSlovenia 473 [3] Similar Biological Medicinal
Products [E] Essential Similarity and Generic Medicinal Product [1] Development of ‘Essentially Similar’ and Scope of Abridged Procedure for Generic Medicinal Products up to October/November 2005 474 xlii 461 461 462 463 464 465 466 466 469 469 470 472 474 474
Table of Contents Meaning of ‘Essential Similarity’ Scope of Application of the Hybrid Abridged Procedure 476 [c] Essential Similarity and Line Extensions [d] Differences in Active Substance [e] Safety and Efficacy Abridged Procedures for Generic Medicinal Products after October 2005 [1] Definition of ‘Generic Product’ (Instead of ‘Essentially Similar’) [a] Same Qualitative and Quantitative Composition [b] Same Pharmaceutical Form [c] Bioequivalence Demonstrated by Studies [d] Salts, Esters, Ethers, Isomers, Mixtures, Complexes, or Derivations [e] The Hybrid Procedure [f] New Active Substance Additional Terms for Protection of Line Extensions [1] Extension for New Therapeutic Indication [a] Justification of New ‘Therapeutic Indication’ [b] Justification of ‘Significant Clinical Benefit’ [2] Extension for New Indications for Well-Established Substances 487 [3] Change of Supply Status [a] [b] [F] [G] 475 478 478 479 480 480 481 481 481 482 482 483 484 485 486 486 §13.04 UK 488 489 Chapter 14 Orphan Medicinal Products Sarah Faircliffe Pieter Erasmus §14.01 Introduction §14.02 The EU Orphan Medicinal Product Regulation §14.03 Applications for Orphan Designation [A] Pre-application Meeting [B] Application Contents and Format [C] COMP [D] Criteria for Orphan Designation [1] Medicinal Product [2] Article 3(1) Requirements [3] Article 3(1) (a) Requirements [a] The Prevalence Criterion [b] The Insufficient Return on Investment Criterion [c] Medical Plausibility [4] Article 3(1) (b) Requirements [a] Existing Satisfactory Method 491 491 492 493 493 494 495 495 495 495 496 496 499 501
501 502 xliii
Table of Contents §14.04 §14.05 §14.06 §14.07 §14.08 §14.09 §14.10 §14.11 [b] Significant Benefit [E] Clinical Data at the Designation Stage [F] Timing of Designation Applications [G] Designation Application Review Procedure and Appeal Process [H] Annual Reports [I] Amendment of a Designation Orphan Medicinal Product MA [A] The Centralised Procedure [B] Review and Confirmation of Orphan Designation Criteria at the Time of MA (‘maintenance review’) Market Exclusivity and Other Incentives [A] Protocol Assistance and Fee Reductions [B] Market Exclusivity [1] Meaning of ‘Similar MedicinalProduct’ [2] ‘Breaking’ Market Exclusivity [3] Procedure for Assessing Similarity and Derogations [4] Impact of a Second Orphan Authorisation Granted under the Derogation Provisions 517 [5] Interpretation of the Market Exclusivity Provisions: European Court Judgments [a] Case T-140/12, Teva v. EMA [b] Case T-452/14 Laboratoires CTRS v. European Commission [c] CaseT-583/13 Shire Pharmaceutical Contracts v. European Commission [C] Market Exclusivity Review:Possible Reduction of Term Transfer of Orphan Designation Transparency Research Future Developments UK (A] Introduction [B] Application for Orphan Designation in Great Britain [C] Market Exclusivity [D] SMEs [E] MA Variation Applications [F] Orphan Register Guidelines/Publications Chapter 15 Biopharmaceuticals Marc Martens, Benedicte Mourisse Sophie Vo §15.01 Introduction §15.02 Specific Nature of Biopharmaceuticals and Consequences xliv 503 506 506 507 508 508 509 509 510 511 511 512 513 514 515 517 517 519 520 522 523 524 524 525 528 528 529
529 530 530 530 531 535 535 536
Table of Contents [A] Biological Starting Materials [B] Product Complexity and Variability [C] Possible Immunogenicity §15.03 Market Access for Innovative Biologicals [A] MAA Routes §15.04 MA Dossier [A] General Requirements Applicable to All Biological Medicinal Products [B] Information Concerning the Active Substance [C] Manufacturing Process of the ActiveSubstance [D] Description and Composition of the FinishedMedicinal Product [E] Non-clinical Aspects §15 .05 Clinical Trials §15 .06 Product-Specific Requirements [A] Plasma-Derived Medicinal Products §15.07 ATMPs §15.08 Vaccines §15.09 Specific Market Surveillance Measures Applicable to Biological Medicinal Products [A] Pharmacovigilance Requirements [B] Changes to the Manufacturing Process §15.10 Regulatory Data Protection §15.11 The EMA’s Biologies Working Party §15.12 Biosimilars [A] Concept of ‘ Biosimilar’ [B] Generics Versus Biosimilars §15.13 ‘Me-Betters’ §15.14 MAA Route §15.15 MAA Dossier Requirements §15.16 Strategic Issues and Next Steps §15.17 UK Chapter 16 Homeopathic, Herbal, and Traditional Herbal Medicinal Products and Cannabis-Based Medicinal Products Pieter Erasmus §16 .01 Introduction §16 .02 Homeopathic Medicinal Products [A] Introduction to Homeopathic Medicinal Products [B] Legal History of Homeopathic Medicinal Products [C] Current Legislative Framework for Homeopathic Medicinal Products [D] Definition of Homeopathic Medicinal Product [E] Homeopathic Simplified Registration Procedure xlv 536 536 537 537 537 538 538 538 539 539 540 541 541 541 543 543 543 543 543 544 545 545 545 546 548 548 549 550
556 559 559 562 562 562 563 564 565
Table of Contents Application Procedure for Homeopathic Simplified Registration Article 16 Authorisation Procedure Applicability of Other Provisions of the Directive to Homeopathic Medicinal Products 567 Herbal and Traditional Herbal Medicinal Products [A] Introduction to Herbal and Traditional Herbal Medicinal Products [B] Herbal Medicinal Products [1] Definition of Herbal Medicinal Products (2) General MA Procedure for Herbal Medicinal Products [C] Traditional Herbal Medicinal Products [1] Current Legislative Framework for Traditional Herbal Medicinal Products [2] Definition of Traditional Herbal Medicinal Products [3] Traditional Use Registration [4] Application Procedure for Traditional UseRegistration [5] Labelling, Package Leaflet, and Advertising of Traditional Herbal Medicinal Products 574 i [6] Other Applicable Provisions for Traditional Use Registration [D] Safety and Efficacy of Herbal and Traditional Herbal Medicinal Products [E] Manufacturing and Quality of Herbal and Traditional Herbal Medicinal Products 576 [F] HMPC [G] EU Herbal Monograph [H] EU List [F] [G] [H] §16.03 §16 .04 Cannabis-Based Medicinal Products §16 .05 UK Chapter 17 Advanced Therapy Medicinal Products Marc Martens, Benedicte Mourisse Sophie Vo §17 .01 Introduction [A] History [B] Definitions [1] Gene Therapy Medicinal Products (Section 2.1, Part IV, Annex I to Directive 2001/83/EC) [2] Somatic Cell Therapy Medicinal Products (Section 2.2, Part IV, Annex I to Directive 2001/83/EC) [3] Tissue-Engineered Products (Article 2(b) of the ATMP Regulation) 588 [C] Combined ATMPs and the Classification
Rules [1] Combined ATMPs xlvi 565 ‘ 567 ; 568: ! 568 : 569 i 569 ‘ 570 ( 570 \ 570 i 571 : 571 572 : ) 575 ; ! 575 576 : 577 j 578 j 579 : 582 [ 585 585 585 587 587 587 589 589 : : । ■ j ί i
Table of Contents [2] Classification Rules §17 .02 Relationship Between the ATMP Regulation and Other European Legislation §17 .03 The Market Access for ATMPS [A] Ordinary Regime [1] The Procedure [2] The CAT [a] Role and Responsibilities [b] Composition [B] Exemptions §17.04 MAA Dossier [A] Specific Requirements Set Out in Part IV of Annex I to Directive 2001/83/EC 597 [B] Other Requirements Applicable toATMPs [1] Summary of Product Characteristics, Labelling, and Package Leaflet 598 [2] GMPs [3] Post-AuthorisationRequirements [a] Follow-Up of Efficacy andRisk Management [b] Traceability §17.05 Incentives for SMEs §17.06 Transitional Period §17.07 UK §17.08 Conclusion 598 599 599 599 600 601 601 601 Chapter 18 Vaccines Marc Martens Phillipas Putter §18.01 Introduction [A] General Overview [B] Vaccines Working Party [C] The EU Vaccines Strategy §18.02 DevelopmentofVaccines [A] Non-clinical Aspects [1] Basic Science Phase [2] Preclinical Testing [B] Clinical Trials [1] Pharmacokinetic/Pharmacodynamic Studies [2] Efficacy and Effectiveness [3] Special Considerations for Vaccine Development [4] Revision of the Guideline of Clinical Evaluation §18.03 MAA [A] The MA Procedures [1] Centralised 603 603 603 604 605 605 606 606 607 608 610 611 612 612 613 613 613 xlvii 590 591 593 593 593 593 594 594 595 597 598
Table of Contents [2] National [3] Decentralisedand Mutual Recognition [B] MAAS [1] Module 1 [2] Module 2 [3] Module 3 [4] Module 4 [5] Module 5 [C] Conditional MA inEmergency Situations §18 .04 The Official Control Authority Batch Release §18 .05 Post-marketing Surveillance: Pharmacovigilance [A] Some Institutions That Ensure Post-Authorisation Safety of Vaccines [B] GVP Module for Vaccines [C] Post-Marketing Authorisation Approval Requirements [1] RMP [2] Variationof the Original VAMF Certificate [3] LicenseRenewals §18.06 Vaccines in the UK [A] Introduction [B] Development of Vaccines in the UK [C] Pre-approval and MA [D] Post-marketing Pharmacovigilance [E] Summary §18 .07 Guidelines/Publications Chapter 19 Medical Devices Kevin Munungu Sophie Vo §19 .01 Introduction §19 .02 Medical Devices [A] Notion of Medical Device [1] Regulatory Definition of a Medical Device [2] Classification of Medical Devices [a] General Principles [b] Classification Rules [B] Placing a Medical Device on the Market in the EU [1] General Safety and Performance Requirements for Marketing of Medical Devices [a] General Requirements Regarding the Design and Manufacture of the Medical Device [b] General Requirements Regarding the Information to Be Supplied with the Device [2] Conformity Assessment Procedures xlviii 613 614 614 614 615 615 616 616 617 617 620 621 622 624 624 624 625 625 625 625 626 627 628 628 631 631 633 633 633 634 634 635 636 636 637 637 638
Table of Contents [a] Role of NotifiedBodies 638 [b] Supporting Evidence 639 [c] CE Marking 640 [d] CE Labelling 641 [e] Registration 642 [3] The Responsibilities of Manufacturers of Medical Devices 642 [C] Post-Market Surveillance, Vigilance, and Market Surveillance 643 [D] Surveillance Role of Member States and Competent Authorities 644 §19.03 In Vitro Diagnostic Medical Devices 644 [A] Notion of in Vitro Diagnostic Medical Device 645 [1] Regulatory Definition of In Vitro Diagnostic Medical Device 645 [2] Classification of In Vitro Diagnostic Medical Devices 646 [B] Placing an In Vitro Diagnostic Medical Device on the Market 647 [1] General Safety and Performance Requirements for Marketing In Vitro Diagnostic Medical Devices 647 [2] Conformity Assessment Procedures 647 §19 .04 How toAdvertise Medical Devices 649 §19 .05 UK 650 [A] Definition of Medical Device 651 [B] Borderline Products 651 [C] Classification of Medical Devices 652 [D] In Vitro Diagnostic Medical Devices 652 [E] Software as Medical Devices 653 [F] Placing Medical Devices on the UKMarket 654 [1] Registration 654 [2] Conformity Assessment Procedures 655 [3] UKCA Marking 655 [4] Post-Market Surveillance,Vigilance, and Market Surveillance 656 §19 .06 How to Advertise Medical Devices 656 Chapter 20 Parallel Trade Christian Lindenthal, Pieter Erasmus Jonathan Edwards §20 .01 Introduction to Parallel Trade §20 .02 Parallel Distribution Law [A] EMA Notice [B] Necessary Licences forParallel Distributors [C] Other Requirements [1] Changes in the Package or Label [2] Notice to Local Authorities [3] MA Updates [4]
Maintenance Notice xlix 657 657 658 658 659 660 660 661 662 662
Table of Contents [5] Quality Control [6] Falsified Medicines §20.03 Parallel Importation [A] Parallel Importation Law [B] The Simplified Procedure [C] General Requirements for the Simplified Procedure §20.04 Intellectual Property Law [A] Introduction [B] Patent Rights and Parallel Trade [1] Exhaustion of Patent Rights [2] Specific Mechanism [C] Trademark Law and Parallel Trade [1] The Repackaging Does Not Affect the Product [2] The Repackaging Is Not Likely toDamage Reputation [3] Indication of the Original Manufacturer and the Repackager [4] Notice to the Trademark Owner [5] The Repackaging Is ‘Necessary’ [6] Burden of Proof [7] Rebranding §20 .05 Competition Law §20 .06 UK [A] Brexit and Exhaustion of IP Rights [B] Implementation in the UK [C] UK Procedure [D] Product Repackaging and Potential Trademark Infringement [E] Notification of Patent Holders Chapter 21 Competition Law in the Pharmaceutical Sector Morten Nissen, Peter Willis Alexander Brachner §21 .01 Introduction §21 .02 Market Definition in the Pharmaceutical Sector [A] Approved Medicines [B] Active Substances [C] Pipeline Products §21.03 Article 101 TFEU [A] The Application of Article 101 ( 1) TFEU [1] The Definition of an Undertaking [2] Definition of Agreements, Concerted Practices, and Decisions of Associations [a] Agreements [b] Concerted Practices [c] Decisions by Association of Undertakings 1 662 663 664 664 665 667 668 668 668 669 670 673 674 675 676 676 677 678 678 679 679 679 680 681 682 683 685 685 685 686 687 687 688 688 688 689 689 690 690
Table of Contents §21.04 §21.05 §21.06 §21.07 §21.08 [3] A Restriction of Competition by Object and/or Effect [4] An Appreciable Restriction of Competition: de Minimis [5] An Appreciable Effect on Trade Between Member States [B] The Application of Article 101 (3) TFEU [1] Individual Exemptions [2] Block Exemptions [a] The TTBER [b] The R D Block Exemption [c] The Damages Directive [C] Selection of Cases/The Pharmaceutical Sector Inquiry [1] Agreements Between Originators and Generics [a] Reverse Payment Patent Settlements [b] Other Agreements Having the Effect of Delaying Generic Market Entry [c] Other Anti-Competitive Agreements Article 102 TFEU [A] Establishing Dominance under Article 102 TFEU [B] Abuse of a Dominant Position [1] Non-price-Based Exclusionary Conduct [a] Misuse of IP Rights [b] Refusal to Supply [c] Other Non-price-Based Exclusionary Abuses [2] Price-based Exclusionary Conduct [a] Fidelity Rebates and Exclusive Purchase Obligations [b] Excessive Pricing Parallel Trade The EU Merger Control Regulation [A] Merger Control Procedure [B] Referral of Concentrations That Do Not Meet the Thresholds [C] Substantive Assessment [1] Horizontal Mergers [2] Non-horizontal Mergers [D] Selection of Cases [1] GlaxoWellcome/Smithkline Beecham [2] Novartis/Hexal State Aid [A] Definition of State Aid under the Treaty [B] Exemptions UK [A] Introduction [B] Merger Control [C] Anti-competitive Behaviour li 691 691 692 692 693 693 694 695 696 697 697 697 699 699 700 701 702 703 703 704 705 706 706 707 707 709 710 711 711 712 712 713 713 714 714 714 715 718 718 720 721
Table of Contents UK Competition Act 1998 Chapter I: Restrictive Agreements [a] Reverse Payment Agreements (Pay-For-Delay) [b] Recent and Ongoing CMA Chapter I Investigations [c] UK Competition Act 1998 Chapter II: Abuse of Dominance [d] Market Definition in Abuse Cases Guidelines/Publications [1] §21.09 Chapter 22 Pandemics and Epidemics Hester Borgers, Fenna Douwenga, Edzard Boonen Phillipas Putter §22.01 Introduction §22.02 Definitions of Pandemic and Epidemic §22.03 The COVID-19 EMA Task Force and Steering Group [A] ETF [B] The EMA COVID-19 Steering Group §22.04 The Commission’s Coronavirus Response Team §22.05 Availability and Market Access of Medicines [A] EMA Executive Steering Group on Shortages and Safety of Medicinal Products [B] EMA Additional Temporary Measures [C] Guidelines and Guidance from the EC on Avoiding Medicines Shortages [D] Recommendation from the EC on Conformity Assessment and Market Surveillance Procedures [E] Compassionate Use §22.06 Clinical Trials Effected by A Pandemic or Epidemic [A] Guidance from the EC and EMA §22.07 Postponement of Regulations (EU) 2017/745 and 2017/746 On Medical Devices §22.08 Vaccine Strategy [A] The EU Vaccine Strategy [B] Advance Purchase Agreements [C] Inclusive Vaccine Alliance §22.09' Healthcare Personnel [A] Exceptions to Work as Healthcare Personnel [B] Cross-Border Migration of Healthcare Personnel Pandemics and Epidemics in the UK §22.10 [A] Vaccine Task Force [B] Clinical Trials and MA [C] Vaccine Development and Strategy lii 721 721 722 723 725 726 729 729 730 731 731 732 732 733 733 734 735 735 736 737 737
738 738 738 739 739 740 740 741 741 742 742 743
Table of Contents Chapter 23 Data Protection in the Pharmaceutical Sector Clara Clark. Nevola Emma Drake §23 .01 Introduction §23 .02 Legal Framework and Penalties [A] Applicable Laws [B] Territorial Scope and Establishment [C] Material Scope of the GDPR [D] Supervision, Enforcement, and Penalties §23.03 The Definition of Personal Data [A] Identifiable [B] Relating [C] Deceased Individuals [D] Special Category Personal Data [1] Generally [2] Data Concerning Health [E] Criminal Convictions and Offence Data [F] Pseudonymised Data [G] Anonymised Data §23.04 Controllers andProcessors [A] Assessing the Roles of the Parties [B] Joint or Separate Control [C] Data Protection Roles in Clinical Trials [1] Site as a Processor [2] Site as a Controller [3] Role of the CRO [4] Other Parties and Data Subjects [D] Controllers and Processors in Contract [1] Processing Agreements [2] Joint Controllers §23 .05 Data Protection Principles §23 .06 Lawfulness [A] Legitimate Interests [1] Identifying a LegitimateInterest [2] Necessity [3] Balancing These InterestsAgainst the Individual’s Rights and Freedoms [B] Consent [1] Freely Given [2] Specific [3] Informed [C] Confidentiality and Consent [D] Consent in Clinical Trials [E] Withdrawing Consent liii 745 745 745 745 746 747 749 749 750 750 751 751 751 752 753 753 754 756 756 758 759 760 760 761 761 762 762 762 763 763 765 765 766 766 767 768 768 768 768 769 770
Table of Contents [F] Quality and Safety Monitoring [G] Research §23.07 Further Processing [A] Compatible Purposes: Research [B] Compatible Purposes: Anonymisation §23. 08 Fairness and Transparency §23. 09 Data Minimisation, Accuracy, andStorage Limitation §23.10 Security and Breach Reporting §23.11 Accountability §23.12 Data Subject Rights [A] Access and Portability [B] Right of Rectification [C] Objection [D] Erasure and Restriction [E] Significant AutomatedDecisions §23.13 Data Transfers §23.14 Marketing to Healthcare Professionals [A] B2B Marketing andB2C Marketing [B] Consent [C] Soft Opt-In 771 ' 772 j 772 : 772 773 774 ■ 776 ' 778 779 780; 781 · 782 [ 782 , 783 ; 784 J 784 786i 786 ; 787; 787‘ Appendix Guidelinesand Publications 789 ; Table of Cases 803 ; EU Directives 823 { Other Legislation 829 ' EU Regulations 835 · Index 839 ΐ liv |
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Summary of Contents About the Editor and Authors v List of Abbreviations Iv Preface bd Chapter 1 Brexit Sally Shorthose 1 Chapter 2 Overview of European Pharmaceutical Regulatory Requirements Sally Shorthose 11 Chapters Overview of Intellectual Property Rights Sally Shorthose, Marta Sznajder Jonathan Edwards 41 Chapter 4 Clinical Trials Sally Shorthose, Pieter Erasmus, Hester Borgers, Edzard Boonen Anna Koster 79 Chapters Obtaining a Marketing Authorisation Sally Shorthose, Sarah Faircliffe Phillipus Putter 147 Chapter 6 Conditional Marketing Authorisations Sally Shorthose Jonathan Edwards 183 xxi
Summary of Contents Chapter 7 Supplementary Protection Certificates Marta Sznajder Jonathan Edwards 201 Chapter 8 Paediatrics Sally Shorthose, Sarah Faircliffe Pieter Erasmus 247 Chapter 9 Advertising Medicinal Products for Human Use Hester Borgers Edzard Boonen (main chapter, the Netherlands); Marc Martens Benedicte Mourisse (Belgium); Alexandre Vuchot, Johanna Harelimana Nour Saab (France); Christian Lindenthal Wolfgang Ernst (Germany); Mauro Turrini (Italy); Coral Ydnez Ana Maria Sdnchez-Valdepefias Ldpez (Spain); Gabriel Lidman Gunnar Hjalt (Sweden); and Sally Shorthose, Sarah Faircliffe Pieter Erasmus (United Kingdom) 279 Chapter 10 Pharmacovigilance Sally Shorthose, Alexandre Vuchot, Pieter Erasmus, Johanna Harelimana Nour Saab 363 Chapter 11 Variations to Marketing Authorisations Alexandre Vuchot, Johanna Harelimana, Nour Saab Phillipas Putter 421 Chapter 12 Combination Products Sarah Faircliffe 447 Chapter 13 Abridged Procedure Pieter Erasmus 461 Chapter 14 Orphan Medicinal Products Sarah Faircliffe Pieter Erasmus 491 Chapter 15 Biopharmaceuticals Marc Martens, Benedicte Mourisse Sophie Vo 535 xxii
Summary of Contents Chapter 16 Homeopathic, Herbal, and Traditional Herbal Medicinal Products and Cannabis-Based Medicinal Products Pieter Erasmus 559 Chapter 17 Advanced Therapy Medicinal Products Marc Martens, Benedicte Mourisse Sophie Vo 585 Chapter 18 Vaccines Marc Martens Phillipas Putter 603 Chapter 19 Medical Devices Kevin Munungu Sophie Vo 631 Chapter 20 Parallel Trade Christian Lindenthal, Pieter Erasmus Jonathan Edwards 657 Chapter 21 Competition Law in the Pharmaceutical Sector Morten Nissen, Peter Willis Alexander Brochner 685 Chapter 22 Pandemics and Epidemics Hester Borgers, Fenna Douwenga, Edzard Boonen Phillipus Putter 729 Chapter 23 Data Protection in the Pharmaceutical Sector Clara Clark. Nevola Emma Drake 745 Appendix Guidelines and Publications 789 Table of Cases 803 EU Directives 823 Other Legislation 829 EU Regulations 835 Index 839 xxiii
Table of Contents About the Editor and Authors v List of Abbreviations Iv Preface Ixi Chapter 1 Brexit Sally Shorthose §1 .01 Introduction [A] Legislation [B] Medicinal Products and the TCA [C] Research [D] Clinical Trials [E] Marketing Authorisations [F] Quality Assurance and Product Safety [G] Pharmacovigilance [H] Regulatory Authorities [I] Parallel Importation §1 .02 Specific Impacts on IPR [A] Unitary Patent System [B] SPCs [C] Trademarks and Registered Community Designs Chapter 2 Overview of European Pharmaceutical Regulatory Requirements Sally Shorthose §2.01 Introduction [A] History of Pharmaceutical Regulation [B] The European Union XXV 1 1 2 2 3 4 4 5 6 6 6 7 7 7 8 11 11 11 13
Table of Contents §2.02 §2.03 §2.04 [C] Major EU Pharmaceutical Legislation [D] Key EU Pharmaceutical Reform Legislation [E] National Law and Interface with EU Directives Definitions [A] Medicinal Product [B] Generic Medicinal Products [C] Paediatric Medicines [D] Orphan Drugs [E] Biotechnology-Derived Medicinal Products [F] Homeopathic Medicinal Products [G] Herbal Medicinal Products [H] Traditional Herbal Medicinal Products [I] Radiopharmaceuticals [J] Non-prescription Medicines [K] Immunological Medicinal Products [L] In-vitro Diagnostic Devices [Μ] Medical Devices The Regulatory Agencies [A] The European Commission [1] DG Health and Consumers (Commonly Known as ‘SANTE’) [2] The EMA [B] Committees of the EMA [1] CHMP [2] CVMP [3] COMP [4] HMPC [5] PDCO [6] CAT [7] PRAC [C] The Heads of Medicines Agencies [D] NCAs of European Member States [E] CMDh [F] European Directorate for the Qualityof Medicines [G] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Applicable EU Legislation, Including Regulations and Guidance [A] EU Treaties [B] Directives [C] Regulations xxvi 14; 15' 15 16 ■ 16 16 16 17: 18 ' 18 18 ■ 19 j 20 ■ 20 21 21 ; 22 : 23 23 23 i 25 ; 26i 26 ! 28 28 i 29 ; 29 j 30 : 31 ; 32■ 32; 33 34; j 34 35 35j 36i 36
Table of Contents §2.05 [D] The Official Journal of the European Communities [E] Guidelines Guidelines/Publications 37 37 39 Chapter 3 Overview of Intellectual Property Rights Sally Shorthose, Marta Sznajder Jonathan Edwards §3.01 Introduction [A] The Importance of IPRs [B] Ownership §3.02 Patents [A] European Patents [1] Patentability and Scope of Protection [a] Requirements [b] Novelty and Inventive Step [c] Scope of Protection [2] Prosecution and Enforcement [a] EPO Opposition Proceedings [b] National Courts [3] Duration [B] Specific Issues Relating to PharmaceuticalPatents [1] Product by Process [2] Products Obtained Directly by a Patented Process [3] New Chemical Entities (NCEs) [4] Composition and Formulation Claims [5] Methods of Treatment [6] Medical Use [7] Biotechnological Inventions [C] Infringement and Defences [1] Bolar Exemption [2] Experimental Use Defence [D] Unitary Patent System [1] The Legislative Framework [a] Legislative Instruments [b] Ratification [2] Unitary Patent [3] UPC [4] Practical Considerations [a] Cost [b] Divisional Applications [c] Opting Out [d] Licences and Technology Transfer Agreements §3.03 SPCs §3.04 Trademarks xxvii 41 41 42 43 43 44 45 45 46 47 48 48 49 49 50 50 50 51 51 51 52 54 56 56 57 57 59 59 60 60 61 62 62 62 62 62 63 63
Table of Contents Registration of Trademarks [1] Routes to Registration [2] Criteria for Registration [a] Absolute Grounds [b] Relative Grounds [3] Duration [B] Regulatory Issues with Pharmaceutical Names [1] International Nonproprietary Names [2] Public Health Concerns andPatientSafety [a] Purely National, Mutual Recognition and Decentralised Procedures [b] Centralised Procedure [C] Trademark Infringement (1] Criteria for Establishing Infringement [2] Parallel Imports §3.05 Copyright, Database Rights, Design Rights [A] Copyright [B] Database Rights [C] Design Rights §3 .06 Confidential Information [A] Chapter 4 Clinical Trials Sally Shorthose, Pieter Erasmus, Hester Borgers, Edzard Boonen Anna Koster §4 .01 Introduction §4 .02 Regulation (EU) No. 536/2014: CTR [A] Introduction to the CTR [B] When the CTR Applies [C] Implementation of the CTR [D] Aims of the CTR §4.03 Authorisation Procedure for a Clinical Trial [A] Introduction to the Authorisation of aClinical Trial [B] CTIS [C] Authorisation Procedure for a Clinical Trial [D] Ethical Committee Approval [1] Introduction [2] Ethical Committee ApprovalProcess [E] Informed Consent §4 .04 The Substantial Modification of a Clinical Trial §4 .05 Start, End, Halt, and Early Termination [A] Start [B] End [C] Halt [D] Early Termination xxviii 64 64 65 65 66 67 68 68 70 70 71 72 72 74 74 74 74 75 76 79 79 81 81 81 82 82 83 83 84 85 90 90 91 93 96 97 98 98 99 100
Table of Contents §4.06 §4.07 §4.08 §4.09 §4.10 §4.11 §4.12 §4.13 §4.14 §4.15 Conduct of the Clinical Trial [A] Introduction to the Conduct of Clinical Trials [BJ GCP Standards [C] Good Manufacturing Practice Clinical Trial Oversight/Role of the sponsor and Investigator [A] Introduction to Clinical Trial Oversight [B] Monitoring [C] GCP Inspection [D] Sponsor and Investigator as the Same Entity [E] Pharmacovigilance Trial Data [A] Introduction to Trial Data [B] Public Access to Trial Data [C] The Trial Master File: Essential Documents [D] Archiving of the Trial Master File [E] Collection of Data [F] Protection of Data and Storage Requirements FIM Studies Following the TGN1412 Case (TeGenero’) [A] Background [B] Revised CHMP Guidelines as a Result of the TeGenero Case Clinical Trials and Patent Legislation: The Bolar and Research Exceptions Introduction to Clinical Trials in the UK [A] Introduction [B] When the UK Regulations Apply [C] Consultation for Legislative Change (2022) Preparing to Apply for CTIMP Authorisation in the UK [A] Introduction [B] The Sponsor and Overview of Sponsor Duties [1] The Sponsor [2] Overview of Sponsor Duties [C] The Investigator, Chief Investigator, and Principal Investigator [D] Registration and Preparing the CTIMP Authorisation Application [E] Requests for MHRA Scientific Advice Approval to Commence a CTIMP in the UK [A] Introduction to the CTIMP Authorisation Process in the UK [B] MHRA CTIMP Authorisation [C] REC Approval [D] HRA Approval Conduct of CTIMPs in the UK UK CTIMP Oversight [A] Introduction to CTIMP Oversight [BJ Monitoring xxix
100 100 101 103 104 104 105 107 108 109 112 112 112 113 114 114 116 118 118 120 121 122 122 122 123 125 125 125 125 125 127 127 129 130 130 130 131 133 133 134 134 134
Table of Contents §4.16 §4.17 §4.18 [C] MHRA GCP Inspections [D] Internal Audit [E] Urgent Safety Measures [F] Pharmacovigilance Amendments, Suspension, and Termination of CTIMPs in the UK [A] Introduction [B] Amendments by the REC or the MHRA [C] Substantial Amendments by the Sponsor [D] Temporary Suspension of CTIMPs [E] Early Termination of CTIMPs [F] End of CTIMPs [G] CTIMP Summary Results CTIMP Data in the UK [A] Introduction [B] Dissemination of CTIMP Results [C] Storage of Trial Master File [D] Access to NHS Electronic Health Records Guidelines/Publications Chapter 5 Obtaining a Marketing Authorisation Sally Shorthose, Sarah Faircliffe Phillipas Putter §5.01 Approval of Medicines for Human Use: Securing a Marketing Authorisation [A] Introduction and Overview of the Processes [B] Goals of the Approval Process: Demonstration of Quality, Safety, and Efficacy [C] Legislative Background [D] Overview of the Application Dossier [E] Overview of the MA Procedures §5.02 Requirements of the Application Dossier [A] Required Contents of an Application Dossier [1] Manufacturing Authorisations [2] Assurance of Quality of All Constituents [3] New Active Substances [4] Certification of Suitability (CEP) [5] Orphan Drugs [6] Naming the Product [7] Required Product Information [8] SmPC [9] Environmental Risks [10] Pharmacovigilance Systems [11] Submission of Test Results [B] Presentation of the Dossier: CTDoc XXX 135 136 136 137 138 138 138 138 140 140 140 141 141 141 141 143 144 145 147 147 147 148 148 150 150 151 152 153 154 154 155 155 155 156 156 157 157 157 158
Table of Contents §5.03 The CP [A] Scope [В] [C] [1] Optional Scope [2] Mandatory Scope Submission to the EMA Application and Approval Procedure: An Overview [1] [D] [E] [F] [G] §5.04 MRP [A] [B] [C] [D] §5.05 §5.06 §5.07 §5.10 Introduction Application Process Dispute Procedure Timing of the Process DCP [A] Introduction [B] Application Process [C] Dispute Procedure [D] Timing of the Procedure The National Procedure [A] Introduction [B] Application Process Summary and Comparison of the Four Procedures [A] [B] [C] §5.08 §5.09 The CHMP [2] Rapporteur of the CHMP [3] CHMP Assessment [4] Commission Decision [5] Withdrawal [6] Publication Marketing a Medicine Special Procedures [1] Compassionate Use [2] Conditional/Exceptional Circumstances Authorisations Timing of the Process Alternatives to the CP The CP MRP The DCP [D] The National Procedure Continuing Validity, Renewal, and Termination of MAs Obtaining MA in the UK [A] Introduction [B] Overview of the MA Procedures in the UK [C] Summary Guidelines/Publications xxxi 159 159 160 160 161 162 163 163 164 165 165 166 166 167 167 167 168 168 168 168 169 170 171 171 171 172 172 172 173 173 173 173 173 175 175 176 177 178 178 178 180 181
Table of Contents Chapter 6 Conditional Marketing Authorisations Sally Shorthose Jonathan. Edwards §6.01 Introduction §6.02 Criteria for a CMA [A] New MAAs [B] Justification That the Medicinal Product Falls Within the Scope of a CMA [1] Seriously Debilitating Diseases or Life-Threatening Diseases [2] Medicinal Products to Be Used in Emergency Situations [a] Influenza Pandemic [b] Bioterrorism [c] COVID-19 Pandemic [3] Orphan Medicinal Products [C] Requirements for a CMA [1] The Risk/Benefit Balance of the Product Is a Positive [2] It Is Likely That the Applicant Will Be Able to Provide Comprehensive Data [3] Fulfilment of Unmet Medical Needs [4] The Benefits to Public Health of Immediate Availability Outweigh the Risks Inherent in the Fact That Additional Data Are Still Required [D] Specific Obligations [E] Timeframe [F] Amendment to Full MA §6.03 Procedure [A] Prior to Submission of a CMA [B] Timing of the Submission and Documentation to Be Supplied [1] Documents to Be Submitted [a] General Requirements [b] Requirements for the Interim Report on the Specific Obligations [c] CHMP Assessment and Opinion [C] CHMP Assessment of a Request for a CMA [D] Information Included in the Summary of Product Characteristics and Package Leaflet [E] EMA Timetable §6.04 MA Granted in Exceptional Circumstances §6.05 United Kingdom §6.06 Guidelines/Publications xxxii 183 183 184 184 185 185 187 187 187 188 189 190 190 190 191 192 192 193 193 •193 193 193 ' 194 194 195 196 ; 196 197 197 197 198 199
Table of Contents Chapter 7 Supplementary Protection Certificates Marta Sznajder Jonathan Edwards §7.01 Introduction §7.02 The Legislation §7.03 Duration and Scope [A] Duration [1] Basic Term [2] Paediatric Extensions for Medicinal Product SPCs [B] Scope [1] What Is a ‘Product’? [2] The Distinction Between a ‘Product’ and a ‘Medicinal Product’ 209 §7.04 The Procedure for Seeking SPC Protection [A] Time Limit [B] Content of the Application [C] Conditions for Obtaining an SPC [D] Entitlement [E] Third-Party Oppositions and Observations §7.05 Infringement and Invalidation §7.06 Transitional Provisions §7.07 Issues in Relation to SPCs [A] When Is a Product ‘Protected by a Basic Patent in Force’? [1] Construction of Patent Claims (21 Combination Products [3] Amendments to the Basic Patent ' [4] Functional Specifications [5] Multiple SPCs Based upon a Single Patent [B] The Product Has Not Already Been the Subjectof a Certificate [C] First Authorisation to Place the Product on the Market as a Medicinal Product [1] ‘First Authorisation’ (2] Date of First Authorisation [D] What Happens When the Basic Patent and MA Have Different Holders? 231 [E] What Form Can an SPC ‘Claim’ Take and What Effect Does It Have on the Scope of Protection Conferred? §7.08 Legislative Changes and Reforms [A] SPC Manufacturing Waiver [B] The Unitary Patent System and SPCs [1] European SPC [2] Unitary SPCs [a] Grant Authority [b] Scope xxxiii 201 201 202 204 204 204 205 206 207 210 210 211 212 212 213 213 214 217 218 218 219 224 225 226 227 228 228 231 232 233 233 234 235 236 236 236
Table of Contents [C] §7.09 UK [A] [B] [C] [D] [E] [c] Brexit [d] Reform Medical Devices [1] Does the Scope of the SPC Regulation Extend to Medical Devices? [2] European Decisions Concerning Class HI Medical Devices [3] Active Implantable Medical Devices [4] Borderline Products [5] Reform Procedure for Seeking SPC Protection Post-Brexit Duration Paediatric Extensions SPC Manufacturing Waiver CJEU Interpretation 237 237 237 238 239 242 242 243 243 244 245 245 246 246 Chapter 8 Paediatrics Sally Shorthose, Sarah Faircliffe Pieter Erasmus §8.01 §8.02 §8.03 §8.04 §8.05 §8.06 Introduction European Regulations Relating to Paediatric Studies [A] Overview of the EU Paediatric Regulation [B] PDCO [C] PIPs [1] PIP Approval Procedures [2] PIP Compliance Check [3] Issues Concerning PIPs [D] PIP Exemptions, Waivers, and Deferrals [1] Exemptions (2] Waivers [3] Deferrals Rewards for PIP Completion [A] The SPC Extension Reward [1] Zero and Negative-Term SPCs [B] Rewards for Orphan Medicinal Products That Comply with Regulation (EC) No. 1901/2006 [C] Free Scientific Advice from EMA Paediatric Use Marketing Authorisation (PUMA) Post-Approval Obligations [A] Duty to Place Product on Market [B] Pharmacovigilance [C] Product Discontinuation [D] The Paediatric Symbol Penalties xxxiv 247 247 248 248 249 250 252 254 255 257 257 257 258 258 258 260 261 263 263 265 265 265 265 266 266
Table of Contents §8.07 §8.08 §8.09 §8.10 §8.11 Transparency Paediatric Research Developments UK [A] Introduction [B] PIP Submissions [C] PIP Modifications [D] PIP Waivers [E] Compliance Checks [F] Completed Paediatric Studies Guidelines/Publications Chapter 9 Advertising Medicinal Products for Human Use Hester Borgers Edzard Boonen (main chapter, the Netherlands); Marc Martens Benedicte Mourisse (Belgium); Alexandre Vuchot, Johanna Harelimana Nour Saab (France); Christian Lindenthal Wolfgang Ernst (Germany); Mauro Turrini (Italy); Coral Ydnez Ana Maria Sdnchez-Valdepenas Ldpez (Spain); Gabriel Lidman Gunnar Hjalt (Sweden); and Sally Shorthose, Sarah Faircliffe Pieter Erasmus (United Kingdom) §9 .01 Introduction §9 .02 Legislative Basis [A] The General Principles [B] Promotion of OTC Medicines [C] What Is Advertising? [D] Internet Advertising [E] Television Advertising [F] European Case Law on Advertisingof Medicinal Products §9.03 Self-Regulation in Europe [A] Advertising of Prescription-OnlyProducts [1] The EFPIA HCP Code [2] Applicability of the EFPIA Code [3] EFPIA Code and Principles for the Use of Digital Channels [B] Advertising of OTC Products §9.04 Implementation in Belgium [A] Legal Basis [B] Sanctions [C] Role of the National Competent Authority [D] Self-Regulation [E] Cases [F] General Advertising Rules §9.05 Implementation in France [A] Legal Bases XXXV 267 267 269 271 271 272 273 274 274 275 275 279 279 282 282 283 285 285 286 286 289 289 289 290 290 290 291 291 291 291 292 293 293 293 293
Table of Contents §9.06 §9.07 §9.08 [1] Binding Rules [2] Non-binding Rules [В] Scope of Application [C] French Legal Requirements [1] Medicinal Products Advertising [a] Medicinal Products Advertising Directed at Healthcare Professionals [b] Medicinal Products Advertising Directed at the Public 297 [2] Medical Devices Advertising [D] Specific Forms of Advertising [1] Meetings and Congresses [2] Advantages and Gifts [3] Samples of Medicinal Products [E] Sanctions [1] Administrative Sanctions [a] Administrative Authorities [b] Control of Advertising Directed at the Public [c] Control of Advertising Directed at Healthcare Professionals [2] Criminal Sanctions Implementation in Germany [A] Legal Basis [B] Scope of the Advertising of Medicinal Products Act [C] National Sanctions [D] Role of the National Competent Authority [E] National Implementation Beyond Requirements of Directive 2001/83/EC [1] Testimonials [2] Internet Presentations [3] Advertising for Telemedicinal Services [4] Further Requirements [F] Self-regulation Implementation in Italy [A] Legal Basis [B] Scope of the Decree [C] Role of the National Competent Authority [D] Self-Regulation for Promotion of Prescription-Only Products [E] Self-Regulation for Promotion of OTC Products [F] General Advertising Rules [G] Regional Control [H] National Sanctions [I] Online Sales of Medicinal Products on the Internet Implementation in The Netherlands xxxvi 293 294 295 296 296 297 297 298 298 298 300 301 301 301 301 302 302 303 303 303 304 305 305 305 306 307 307 308 308 308 308 309 310 310 310 311 311 311 312
Table of Contents [A] §9.09 Legal Basis [1] The Dutch Medicines Act [a] Enforcement [b] Sanctions [c] Inspections [d] Cooperation with Other Regulating Institutes [В] Civil Law [C] Criminal Law [D] Self-regulation [1] Enforcement [2] Sanctions [3] Code of Conduct Pharmaceutical Advertising [a] Information [b] Comparative Advertising [c] Samples [d] Internet Advertising [4] OTC Advertising Code [5] Inducement [a] Gifts [b] Hospitality [c] Sponsoring and Grants [d] Services [E] Medical Devices [F] Healthcare Products Implementation in Spain [A] Regulatory Aspects [1] Legal Basis [2] The General Principles as Interpreted by Spanish Authorities [3] Advertising Aimed at Persons Qualified to Prescribe or Supply Medicinal Products 325 [a] Advertising Using the Internet [4] Advertising Aimed at the General Public [B] Infringements and Remedies under the Law [C] Self-regulation [1] Spanish Code of Good Practice for the Pharmaceutical Industry [a] Promotion of Medicines and Interaction with Healthcare Professionals 332 [b] Relationships Between the Pharmaceutical Industry and Patient Organisations 334 [2] Spanish Code of Good Practices for the Promotion and Advertising of Non-Prescription Medicinal Products 335 [D] Infringements and Remedies under the Farmaindustria Code xxxvii 312 312 313 313 314 315 315 316 316 316 317 317 318 319 319 319 320 320 321 321 322 322 323 323 324 324 324 325 326 327 328 332 332 335
Table of Contents Implementation in Sweden [A] Legal Basis [B] Scope of the Regulations [C] Role of the MPA: The National Competent Authority [1] Complaints to the MPA [2] Sanctions [D] Self-Regulation [1] The LIF [2] The EthicalRules [3] The IGN andthe NBL [4] The IGN [5] The NBL [6] Agreements on Forms of Collaboration with the Healthcare Sector [7] Other Applicable Rules §9.11 Implementation in the UK [A] Legal Basis [B] Scope of the Regulations [C] Regulation by the MHRA [1] The Blue Guide [2] Advertising Using the Internet [3] Complaints to the MHRA [D] Sanctions [E] Self-Regulation [1] The Association of the British Pharmaceutical Industry (ABPI) and PMCPA [2] PAGB [a] The PAGB Consumer Code [b] The PAGB Professional Code [F] ASA [G] Association of British HealthcareIndustries (ABHI) Annex: Case Histories §9.10 Chapter 10 Pharmacovigilance Sally Shorthose, Alexandre Vuchot, Pieter Erasmus, Johanna Harelimana Nour Saab §10 .01 Introduction and Background §10 .02 Pre-authorisation Pharmacovigilance [A] Legislative Framework [B] First-in-Man Trials [1] Case Study 1 [C] Clinical Trials in Patients [D] The Investigator Brochure xxxviii 336 336 338 338 338 339 339 340 340 341 341 342 343 344 344 344 346 347 347 347 349 350 351 352. 354 355 355 356 357 358 363 363 367 368 370 371 371 372
Table of Contents §10.03 §10.04 §10.05 §10.06 §10.07 §10.08 [E] Reporting SUSARs The Marketing Authorisation Application [AJ Legislative Framework [B] The Requirements Set Out in Directive 2001/83/EC [C] The Reporting of Adverse Reactions [1] Reports to the ΜΑΗ [2] Reports from Patients/Consumers [3] Reports with Name of Active Substance Only [4] Literature Reports [5] Reports from Non-Medical Sources [6] Timescales for Expedited Reporting [7] MedDRA [8] Electronic Reporting [9] Pregnancy Registries [10] Lack of Efficacy [11] Abuse, Misuse, or Overdose [12] Public Health Emergency PSURs [A] Introduction [B] Contents of the PSUR [C] Periodicity of Submission of PSUR [D] PSUR Work-Sharing Initiative The Pharmacovigilance Activities of the Key Parties [A] The EMA [B] Pharmacovigilance Working Party [C] Competent Authorities of the Member States Risk Management and EU-RMP [A] Introduction [B] Content of the EU-RMP [C] Monitoring of the Risk/Benefit Balance and Identification of Safety Signals [D] Risk Management at the MAH's Initiative [E] Risk Management at the EMA’s Initiative [1] Case Study 2: Cerivastatin (Lipobay) Withdrawal [F] Risk Management at National Competent Authorities’ Initiative [1] Case Study 3: Bupropion Compliance with Pharmacovigilance Obligations [A] Legal Basis for Pharmacovigilance Inspections [B] Composition of the Inspection Team [C] Timing of Inspections [D] Conduct of Pharmacovigilance Inspections [E] Common Findings of Inspections [F] Sanctions Summary of Recent Changes xxxix 372 372 373 375 377 377 378 379 379 380 380 381 381 382 382 382 382 383 383
383 384 385 386 386 387 387 390 390 391 392 392 393 394 395 396 396 397 398 399 400 401 403 405
Table of Contents [A] [B] [C] [D] §10.09 §10.10 Pharmacovigilance System Master File Coordination and Inspection: PRAC PASS and PAES Specific Conditions Relating to PhV affecting EMA [1] PSUR Requirements [2] Set-Up of Interconnected Web Portals [3] GVP Guidelines 405 ; 406 ; 408 409 : 409 : 410 1 410 ; 410 i UK [A] [B] [C] [D] [E] [F] [G] [H] [I] [J] Introduction Submission and Receipt of ICSRs Signal Detection Risk Management Plans (RMPs) Periodic Safety Update Reports (PSURs) Post Authorisation Safety Studies (PASS) Safety Referrals Major Safety Reviews Post-authorisation Measures (PAMs) Implementation of Outcomes of EU Referrals and Procedures Concerning PSURs, PASS, Signal Assessments and PAMs [K] Requirements for MAs Granted via the Unfettered Access route [L] Submitting ICSRS [Μ] Provision of Other Pharmacovigilance Data Guidelines/Publications Chapter 11 Variations to Marketing Authorisations Alexandre Vuchot, Johanna Harelimana, Nour Saab Phillipas Putter §11.01 Reason for Variations [A] Changes Not Requiring a Variation [B] Variation Legislation § 11.02 Classification of Changes [A] Types IA and IB [1] Type IA [2] Type IB [3] Re-classification of Type IA and Type IB Variations [B] Type II [1] Definition [2] Type II Categories [3] The International Council on Harmonisation (ICH) Design Space Concept [a] Introduction [b] Process Analytical Technology (PAT) [c] Quality Risk Management [C] Extensions xl 410 : 412 ; 413 413 j 414 i 415 ' 416 : 417 417 418 418 418 418 418 421 421 422 422 423 423 423 425 425 425 425 425 426 426 427 427 427
Table of Contents [1] Changes in Pharmaceutical Form [2] Changes in Strength [D] Classification of Unforeseen Variations §11.03 Substantive Requirements of the Variation Application [A] Variation Applications for Biological Medicinal Products [1] Issues Arising in Relation to Biologicals [2] Regulatory Guidelines [a] Quality Guidelines [b] Safety and Efficacy Requirements §11.04 Variation Application Procedure [A] Forms and Format [B] Grouping of Applications [1] Grouping of Variations Granted under the Mutual Recognition, Decentralised and CentralisedProcedures [2] Grouping of Variations to Purely National MAs [C] Work-Sharing Procedure [D] Products Authorised Through Mutual Recognition [1] Type IA [2] Type IB [3] Type II [E] Centrally Authorised Products [1] Advance Notice [2] Type IA and IB Variations [3] Type II Variations [F] Purely National Procedure [1] Type IA Variations [2] Type IB Variations [3] Type II Variations [G] Urgent Safety Restrictions [H] Human Influenza Vaccines [I] Human Coronavirus Vaccines §11.05 Variations to MAs in the UK [A] Introduction [B] Variation Procedure in the UK [C] Northern Ireland [D] Summary 428 428 429 429 430 430 430 431 431 432 432 433 433 434 434 436 436 437 438 439 439 439 439 441 441 441 441 442 443 443 443 443 444 446 446 Chapter 12 Combination Products Sarah Faircliffe 447 §12.01 Introduction 447 [A] Combination Products 447 [B] Combination Products: Requirement for a MA and Regulatory Data Protection 448 xli
Table of Contents Requirements for Marketing Approval of Fixed-Combination Medicinal Products 450 [A] The Application Dossier 450 [B] The Application Procedure 450 [C] Scientific References, Non-Clinical Tests, and Clinical Trials 451 [D] Necessity for Non-Clinical Tests and Clinical Trials 452 [1] Situations Where Additional Studies Are Necessary 452 [2] Situations Where Fewer Studies Are Necessary 453 [a] Combinations Already in Widespread Use as Free Combination Therapy 453 [b] Combination of Components Already Approved as a Fixed-Combination Product 455 §12.03 Criteria for Approval of Fixed-Combination Products 455 [A] The Risk/Benefit Ratio 455 [B] Relevance of Each Active Substance of the Combination 457 [C] Relevance of the Specific Dosage Regime 457 §12 .04 UK 457 §12 .05 Guidelines/Publications 458 §12.02 Chapter 13 Abridged Procedure Pieter Erasmus §13 .01 Introduction §13 .02 Three Types of Abridged Procedures [A] Abridged Procedure Based on Cross-Reference to Data with Holder’s Consent [B] Abridged Procedure Based on Bibliographic Application for Well-Established Use 464 [1] Well-Established Medicinal Use [2] Ten Years of Use §13.03 Abridged Procedure for Generic Products [A] Data Protection of a Registration File for Six or Ten Years [B] Data Protection and Marketing Exclusivity, 8 + 2 Years [C] Data Protection Rules Applicable Within the EU until 30 October 2015 [D] European Reference Medicinal Product [1] Global MA [2] Reference to Products Authorised in the Member States: Cyprus, Lithuania, Malta, Poland, andSlovenia 473 [3] Similar Biological Medicinal
Products [E] Essential Similarity and Generic Medicinal Product [1] Development of ‘Essentially Similar’ and Scope of Abridged Procedure for Generic Medicinal Products up to October/November 2005 474 xlii 461 461 462 463 464 465 466 466 469 469 470 472 474 474
Table of Contents Meaning of ‘Essential Similarity’ Scope of Application of the Hybrid Abridged Procedure 476 [c] Essential Similarity and Line Extensions [d] Differences in Active Substance [e] Safety and Efficacy Abridged Procedures for Generic Medicinal Products after October 2005 [1] Definition of ‘Generic Product’ (Instead of ‘Essentially Similar’) [a] Same Qualitative and Quantitative Composition [b] Same Pharmaceutical Form [c] Bioequivalence Demonstrated by Studies [d] Salts, Esters, Ethers, Isomers, Mixtures, Complexes, or Derivations [e] The Hybrid Procedure [f] New Active Substance Additional Terms for Protection of Line Extensions [1] Extension for New Therapeutic Indication [a] Justification of New ‘Therapeutic Indication’ [b] Justification of ‘Significant Clinical Benefit’ [2] Extension for New Indications for Well-Established Substances 487 [3] Change of Supply Status [a] [b] [F] [G] 475 478 478 479 480 480 481 481 481 482 482 483 484 485 486 486 §13.04 UK 488 489 Chapter 14 Orphan Medicinal Products Sarah Faircliffe Pieter Erasmus §14.01 Introduction §14.02 The EU Orphan Medicinal Product Regulation §14.03 Applications for Orphan Designation [A] Pre-application Meeting [B] Application Contents and Format [C] COMP [D] Criteria for Orphan Designation [1] Medicinal Product [2] Article 3(1) Requirements [3] Article 3(1) (a) Requirements [a] The Prevalence Criterion [b] The Insufficient Return on Investment Criterion [c] Medical Plausibility [4] Article 3(1) (b) Requirements [a] Existing Satisfactory Method 491 491 492 493 493 494 495 495 495 495 496 496 499 501
501 502 xliii
Table of Contents §14.04 §14.05 §14.06 §14.07 §14.08 §14.09 §14.10 §14.11 [b] Significant Benefit [E] Clinical Data at the Designation Stage [F] Timing of Designation Applications [G] Designation Application Review Procedure and Appeal Process [H] Annual Reports [I] Amendment of a Designation Orphan Medicinal Product MA [A] The Centralised Procedure [B] Review and Confirmation of Orphan Designation Criteria at the Time of MA (‘maintenance review’) Market Exclusivity and Other Incentives [A] Protocol Assistance and Fee Reductions [B] Market Exclusivity [1] Meaning of ‘Similar MedicinalProduct’ [2] ‘Breaking’ Market Exclusivity [3] Procedure for Assessing Similarity and Derogations [4] Impact of a Second Orphan Authorisation Granted under the Derogation Provisions 517 [5] Interpretation of the Market Exclusivity Provisions: European Court Judgments [a] Case T-140/12, Teva v. EMA [b] Case T-452/14 Laboratoires CTRS v. European Commission [c] CaseT-583/13 Shire Pharmaceutical Contracts v. European Commission [C] Market Exclusivity Review:Possible Reduction of Term Transfer of Orphan Designation Transparency Research Future Developments UK (A] Introduction [B] Application for Orphan Designation in Great Britain [C] Market Exclusivity [D] SMEs [E] MA Variation Applications [F] Orphan Register Guidelines/Publications Chapter 15 Biopharmaceuticals Marc Martens, Benedicte Mourisse Sophie Vo §15.01 Introduction §15.02 Specific Nature of Biopharmaceuticals and Consequences xliv 503 506 506 507 508 508 509 509 510 511 511 512 513 514 515 517 517 519 520 522 523 524 524 525 528 528 529
529 530 530 530 531 535 535 536
Table of Contents [A] Biological Starting Materials [B] Product Complexity and Variability [C] Possible Immunogenicity §15.03 Market Access for Innovative Biologicals [A] MAA Routes §15.04 MA Dossier [A] General Requirements Applicable to All Biological Medicinal Products [B] Information Concerning the Active Substance [C] Manufacturing Process of the ActiveSubstance [D] Description and Composition of the FinishedMedicinal Product [E] Non-clinical Aspects §15 .05 Clinical Trials §15 .06 Product-Specific Requirements [A] Plasma-Derived Medicinal Products §15.07 ATMPs §15.08 Vaccines §15.09 Specific Market Surveillance Measures Applicable to Biological Medicinal Products [A] Pharmacovigilance Requirements [B] Changes to the Manufacturing Process §15.10 Regulatory Data Protection §15.11 The EMA’s Biologies Working Party §15.12 Biosimilars [A] Concept of ‘ Biosimilar’ [B] Generics Versus Biosimilars §15.13 ‘Me-Betters’ §15.14 MAA Route §15.15 MAA Dossier Requirements §15.16 Strategic Issues and Next Steps §15.17 UK Chapter 16 Homeopathic, Herbal, and Traditional Herbal Medicinal Products and Cannabis-Based Medicinal Products Pieter Erasmus §16 .01 Introduction §16 .02 Homeopathic Medicinal Products [A] Introduction to Homeopathic Medicinal Products [B] Legal History of Homeopathic Medicinal Products [C] Current Legislative Framework for Homeopathic Medicinal Products [D] Definition of Homeopathic Medicinal Product [E] Homeopathic Simplified Registration Procedure xlv 536 536 537 537 537 538 538 538 539 539 540 541 541 541 543 543 543 543 543 544 545 545 545 546 548 548 549 550
556 559 559 562 562 562 563 564 565
Table of Contents Application Procedure for Homeopathic Simplified Registration Article 16 Authorisation Procedure Applicability of Other Provisions of the Directive to Homeopathic Medicinal Products 567 Herbal and Traditional Herbal Medicinal Products [A] Introduction to Herbal and Traditional Herbal Medicinal Products [B] Herbal Medicinal Products [1] Definition of Herbal Medicinal Products (2) General MA Procedure for Herbal Medicinal Products [C] Traditional Herbal Medicinal Products [1] Current Legislative Framework for Traditional Herbal Medicinal Products [2] Definition of Traditional Herbal Medicinal Products [3] Traditional Use Registration [4] Application Procedure for Traditional UseRegistration [5] Labelling, Package Leaflet, and Advertising of Traditional Herbal Medicinal Products 574 i [6] Other Applicable Provisions for Traditional Use Registration [D] Safety and Efficacy of Herbal and Traditional Herbal Medicinal Products [E] Manufacturing and Quality of Herbal and Traditional Herbal Medicinal Products 576 [F] HMPC [G] EU Herbal Monograph [H] EU List [F] [G] [H] §16.03 §16 .04 Cannabis-Based Medicinal Products §16 .05 UK Chapter 17 Advanced Therapy Medicinal Products Marc Martens, Benedicte Mourisse Sophie Vo §17 .01 Introduction [A] History [B] Definitions [1] Gene Therapy Medicinal Products (Section 2.1, Part IV, Annex I to Directive 2001/83/EC) [2] Somatic Cell Therapy Medicinal Products (Section 2.2, Part IV, Annex I to Directive 2001/83/EC) [3] Tissue-Engineered Products (Article 2(b) of the ATMP Regulation) 588 [C] Combined ATMPs and the Classification
Rules [1] Combined ATMPs xlvi 565 ‘ 567 ; 568: ! 568 : 569 i 569 ‘ 570 ( 570 \ 570 i 571 : 571 572 : ) 575 ; ! 575 576 : 577 j 578 j 579 : 582 [ 585 585 585 587 587 587 589 589 : : । ■ j ί i
Table of Contents [2] Classification Rules §17 .02 Relationship Between the ATMP Regulation and Other European Legislation §17 .03 The Market Access for ATMPS [A] Ordinary Regime [1] The Procedure [2] The CAT [a] Role and Responsibilities [b] Composition [B] Exemptions §17.04 MAA Dossier [A] Specific Requirements Set Out in Part IV of Annex I to Directive 2001/83/EC 597 [B] Other Requirements Applicable toATMPs [1] Summary of Product Characteristics, Labelling, and Package Leaflet 598 [2] GMPs [3] Post-AuthorisationRequirements [a] Follow-Up of Efficacy andRisk Management [b] Traceability §17.05 Incentives for SMEs §17.06 Transitional Period §17.07 UK §17.08 Conclusion 598 599 599 599 600 601 601 601 Chapter 18 Vaccines Marc Martens Phillipas Putter §18.01 Introduction [A] General Overview [B] Vaccines Working Party [C] The EU Vaccines Strategy §18.02 DevelopmentofVaccines [A] Non-clinical Aspects [1] Basic Science Phase [2] Preclinical Testing [B] Clinical Trials [1] Pharmacokinetic/Pharmacodynamic Studies [2] Efficacy and Effectiveness [3] Special Considerations for Vaccine Development [4] Revision of the Guideline of Clinical Evaluation §18.03 MAA [A] The MA Procedures [1] Centralised 603 603 603 604 605 605 606 606 607 608 610 611 612 612 613 613 613 xlvii 590 591 593 593 593 593 594 594 595 597 598
Table of Contents [2] National [3] Decentralisedand Mutual Recognition [B] MAAS [1] Module 1 [2] Module 2 [3] Module 3 [4] Module 4 [5] Module 5 [C] Conditional MA inEmergency Situations §18 .04 The Official Control Authority Batch Release §18 .05 Post-marketing Surveillance: Pharmacovigilance [A] Some Institutions That Ensure Post-Authorisation Safety of Vaccines [B] GVP Module for Vaccines [C] Post-Marketing Authorisation Approval Requirements [1] RMP [2] Variationof the Original VAMF Certificate [3] LicenseRenewals §18.06 Vaccines in the UK [A] Introduction [B] Development of Vaccines in the UK [C] Pre-approval and MA [D] Post-marketing Pharmacovigilance [E] Summary §18 .07 Guidelines/Publications Chapter 19 Medical Devices Kevin Munungu Sophie Vo §19 .01 Introduction §19 .02 Medical Devices [A] Notion of Medical Device [1] Regulatory Definition of a Medical Device [2] Classification of Medical Devices [a] General Principles [b] Classification Rules [B] Placing a Medical Device on the Market in the EU [1] General Safety and Performance Requirements for Marketing of Medical Devices [a] General Requirements Regarding the Design and Manufacture of the Medical Device [b] General Requirements Regarding the Information to Be Supplied with the Device [2] Conformity Assessment Procedures xlviii 613 614 614 614 615 615 616 616 617 617 620 621 622 624 624 624 625 625 625 625 626 627 628 628 631 631 633 633 633 634 634 635 636 636 637 637 638
Table of Contents [a] Role of NotifiedBodies 638 [b] Supporting Evidence 639 [c] CE Marking 640 [d] CE Labelling 641 [e] Registration 642 [3] The Responsibilities of Manufacturers of Medical Devices 642 [C] Post-Market Surveillance, Vigilance, and Market Surveillance 643 [D] Surveillance Role of Member States and Competent Authorities 644 §19.03 In Vitro Diagnostic Medical Devices 644 [A] Notion of in Vitro Diagnostic Medical Device 645 [1] Regulatory Definition of In Vitro Diagnostic Medical Device 645 [2] Classification of In Vitro Diagnostic Medical Devices 646 [B] Placing an In Vitro Diagnostic Medical Device on the Market 647 [1] General Safety and Performance Requirements for Marketing In Vitro Diagnostic Medical Devices 647 [2] Conformity Assessment Procedures 647 §19 .04 How toAdvertise Medical Devices 649 §19 .05 UK 650 [A] Definition of Medical Device 651 [B] Borderline Products 651 [C] Classification of Medical Devices 652 [D] In Vitro Diagnostic Medical Devices 652 [E] Software as Medical Devices 653 [F] Placing Medical Devices on the UKMarket 654 [1] Registration 654 [2] Conformity Assessment Procedures 655 [3] UKCA Marking 655 [4] Post-Market Surveillance,Vigilance, and Market Surveillance 656 §19 .06 How to Advertise Medical Devices 656 Chapter 20 Parallel Trade Christian Lindenthal, Pieter Erasmus Jonathan Edwards §20 .01 Introduction to Parallel Trade §20 .02 Parallel Distribution Law [A] EMA Notice [B] Necessary Licences forParallel Distributors [C] Other Requirements [1] Changes in the Package or Label [2] Notice to Local Authorities [3] MA Updates [4]
Maintenance Notice xlix 657 657 658 658 659 660 660 661 662 662
Table of Contents [5] Quality Control [6] Falsified Medicines §20.03 Parallel Importation [A] Parallel Importation Law [B] The Simplified Procedure [C] General Requirements for the Simplified Procedure §20.04 Intellectual Property Law [A] Introduction [B] Patent Rights and Parallel Trade [1] Exhaustion of Patent Rights [2] Specific Mechanism [C] Trademark Law and Parallel Trade [1] The Repackaging Does Not Affect the Product [2] The Repackaging Is Not Likely toDamage Reputation [3] Indication of the Original Manufacturer and the Repackager [4] Notice to the Trademark Owner [5] The Repackaging Is ‘Necessary’ [6] Burden of Proof [7] Rebranding §20 .05 Competition Law §20 .06 UK [A] Brexit and Exhaustion of IP Rights [B] Implementation in the UK [C] UK Procedure [D] Product Repackaging and Potential Trademark Infringement [E] Notification of Patent Holders Chapter 21 Competition Law in the Pharmaceutical Sector Morten Nissen, Peter Willis Alexander Brachner §21 .01 Introduction §21 .02 Market Definition in the Pharmaceutical Sector [A] Approved Medicines [B] Active Substances [C] Pipeline Products §21.03 Article 101 TFEU [A] The Application of Article 101 ( 1) TFEU [1] The Definition of an Undertaking [2] Definition of Agreements, Concerted Practices, and Decisions of Associations [a] Agreements [b] Concerted Practices [c] Decisions by Association of Undertakings 1 662 663 664 664 665 667 668 668 668 669 670 673 674 675 676 676 677 678 678 679 679 679 680 681 682 683 685 685 685 686 687 687 688 688 688 689 689 690 690
Table of Contents §21.04 §21.05 §21.06 §21.07 §21.08 [3] A Restriction of Competition by Object and/or Effect [4] An Appreciable Restriction of Competition: de Minimis [5] An Appreciable Effect on Trade Between Member States [B] The Application of Article 101 (3) TFEU [1] Individual Exemptions [2] Block Exemptions [a] The TTBER [b] The R D Block Exemption [c] The Damages Directive [C] Selection of Cases/The Pharmaceutical Sector Inquiry [1] Agreements Between Originators and Generics [a] Reverse Payment Patent Settlements [b] Other Agreements Having the Effect of Delaying Generic Market Entry [c] Other Anti-Competitive Agreements Article 102 TFEU [A] Establishing Dominance under Article 102 TFEU [B] Abuse of a Dominant Position [1] Non-price-Based Exclusionary Conduct [a] Misuse of IP Rights [b] Refusal to Supply [c] Other Non-price-Based Exclusionary Abuses [2] Price-based Exclusionary Conduct [a] Fidelity Rebates and Exclusive Purchase Obligations [b] Excessive Pricing Parallel Trade The EU Merger Control Regulation [A] Merger Control Procedure [B] Referral of Concentrations That Do Not Meet the Thresholds [C] Substantive Assessment [1] Horizontal Mergers [2] Non-horizontal Mergers [D] Selection of Cases [1] GlaxoWellcome/Smithkline Beecham [2] Novartis/Hexal State Aid [A] Definition of State Aid under the Treaty [B] Exemptions UK [A] Introduction [B] Merger Control [C] Anti-competitive Behaviour li 691 691 692 692 693 693 694 695 696 697 697 697 699 699 700 701 702 703 703 704 705 706 706 707 707 709 710 711 711 712 712 713 713 714 714 714 715 718 718 720 721
Table of Contents UK Competition Act 1998 Chapter I: Restrictive Agreements [a] Reverse Payment Agreements (Pay-For-Delay) [b] Recent and Ongoing CMA Chapter I Investigations [c] UK Competition Act 1998 Chapter II: Abuse of Dominance [d] Market Definition in Abuse Cases Guidelines/Publications [1] §21.09 Chapter 22 Pandemics and Epidemics Hester Borgers, Fenna Douwenga, Edzard Boonen Phillipas Putter §22.01 Introduction §22.02 Definitions of Pandemic and Epidemic §22.03 The COVID-19 EMA Task Force and Steering Group [A] ETF [B] The EMA COVID-19 Steering Group §22.04 The Commission’s Coronavirus Response Team §22.05 Availability and Market Access of Medicines [A] EMA Executive Steering Group on Shortages and Safety of Medicinal Products [B] EMA Additional Temporary Measures [C] Guidelines and Guidance from the EC on Avoiding Medicines Shortages [D] Recommendation from the EC on Conformity Assessment and Market Surveillance Procedures [E] Compassionate Use §22.06 Clinical Trials Effected by A Pandemic or Epidemic [A] Guidance from the EC and EMA §22.07 Postponement of Regulations (EU) 2017/745 and 2017/746 On Medical Devices §22.08 Vaccine Strategy [A] The EU Vaccine Strategy [B] Advance Purchase Agreements [C] Inclusive Vaccine Alliance §22.09' Healthcare Personnel [A] Exceptions to Work as Healthcare Personnel [B] Cross-Border Migration of Healthcare Personnel Pandemics and Epidemics in the UK §22.10 [A] Vaccine Task Force [B] Clinical Trials and MA [C] Vaccine Development and Strategy lii 721 721 722 723 725 726 729 729 730 731 731 732 732 733 733 734 735 735 736 737 737
738 738 738 739 739 740 740 741 741 742 742 743
Table of Contents Chapter 23 Data Protection in the Pharmaceutical Sector Clara Clark. Nevola Emma Drake §23 .01 Introduction §23 .02 Legal Framework and Penalties [A] Applicable Laws [B] Territorial Scope and Establishment [C] Material Scope of the GDPR [D] Supervision, Enforcement, and Penalties §23.03 The Definition of Personal Data [A] Identifiable [B] Relating [C] Deceased Individuals [D] Special Category Personal Data [1] Generally [2] Data Concerning Health [E] Criminal Convictions and Offence Data [F] Pseudonymised Data [G] Anonymised Data §23.04 Controllers andProcessors [A] Assessing the Roles of the Parties [B] Joint or Separate Control [C] Data Protection Roles in Clinical Trials [1] Site as a Processor [2] Site as a Controller [3] Role of the CRO [4] Other Parties and Data Subjects [D] Controllers and Processors in Contract [1] Processing Agreements [2] Joint Controllers §23 .05 Data Protection Principles §23 .06 Lawfulness [A] Legitimate Interests [1] Identifying a LegitimateInterest [2] Necessity [3] Balancing These InterestsAgainst the Individual’s Rights and Freedoms [B] Consent [1] Freely Given [2] Specific [3] Informed [C] Confidentiality and Consent [D] Consent in Clinical Trials [E] Withdrawing Consent liii 745 745 745 745 746 747 749 749 750 750 751 751 751 752 753 753 754 756 756 758 759 760 760 761 761 762 762 762 763 763 765 765 766 766 767 768 768 768 768 769 770
Table of Contents [F] Quality and Safety Monitoring [G] Research §23.07 Further Processing [A] Compatible Purposes: Research [B] Compatible Purposes: Anonymisation §23. 08 Fairness and Transparency §23. 09 Data Minimisation, Accuracy, andStorage Limitation §23.10 Security and Breach Reporting §23.11 Accountability §23.12 Data Subject Rights [A] Access and Portability [B] Right of Rectification [C] Objection [D] Erasure and Restriction [E] Significant AutomatedDecisions §23.13 Data Transfers §23.14 Marketing to Healthcare Professionals [A] B2B Marketing andB2C Marketing [B] Consent [C] Soft Opt-In 771 ' 772 j 772 : 772 773 774 ■ 776 ' 778 779 780; 781 · 782 [ 782 , 783 ; 784 J 784 786i 786 ; 787; 787‘ Appendix Guidelinesand Publications 789 ; Table of Cases 803 ; EU Directives 823 { Other Legislation 829 ' EU Regulations 835 · Index 839 ΐ liv |
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| spelling | Guide to EU pharmaceutical regulatory law Guide to EU and UK pharmaceutical regulatory law edited by Sally Shorthose Eighth edition Alphen aan den Rijn Wolters Kluwer [2023] lxv, 852 Seiten 25 cm txt rdacontent n rdamedia nc rdacarrier All previous editions were published under the title: Guide to EU pharmaceutical regulatory law Europäische Union (DE-588)5098525-5 gnd rswk-swf Vergaberecht (DE-588)7574511-2 gnd rswk-swf Regulierung (DE-588)4201190-5 gnd rswk-swf Pharmazeutische Industrie (DE-588)4045696-1 gnd rswk-swf Großbritannien (DE-588)4022153-2 gnd rswk-swf Drugs / Marketing / Law and legislation / European Union countries Drugs / Marketing / Law and legislation / Great Britain Drugs / Law and legislation / European Union countries Drugs / Law and legislation / Great Britain Pharmacy / Law and legislation / European Union countries Pharmacy / Law and legislation / Great Britain Drugs / Law and legislation Drugs / Marketing / Law and legislation Pharmacy / Law and legislation European Union countries Great Britain (DE-588)4143413-4 Aufsatzsammlung gnd-content Europäische Union (DE-588)5098525-5 b Großbritannien (DE-588)4022153-2 g Pharmazeutische Industrie (DE-588)4045696-1 s Regulierung (DE-588)4201190-5 s Vergaberecht (DE-588)7574511-2 s DE-604 Shorthose, Sally (DE-588)1284199746 edt Erscheint auch als Online-Ausgabe 978-94-035-3023-9 Erscheint auch als Online-Ausgabe, PDF 978-94-035-3024-6 Digitalisierung UB Passau - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034250988&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Guide to EU and UK pharmaceutical regulatory law Europäische Union (DE-588)5098525-5 gnd Vergaberecht (DE-588)7574511-2 gnd Regulierung (DE-588)4201190-5 gnd Pharmazeutische Industrie (DE-588)4045696-1 gnd |
| subject_GND | (DE-588)5098525-5 (DE-588)7574511-2 (DE-588)4201190-5 (DE-588)4045696-1 (DE-588)4022153-2 (DE-588)4143413-4 |
| title | Guide to EU and UK pharmaceutical regulatory law |
| title_alt | Guide to EU pharmaceutical regulatory law |
| title_auth | Guide to EU and UK pharmaceutical regulatory law |
| title_exact_search | Guide to EU and UK pharmaceutical regulatory law |
| title_exact_search_txtP | Guide to EU and UK pharmaceutical regulatory law |
| title_full | Guide to EU and UK pharmaceutical regulatory law edited by Sally Shorthose |
| title_fullStr | Guide to EU and UK pharmaceutical regulatory law edited by Sally Shorthose |
| title_full_unstemmed | Guide to EU and UK pharmaceutical regulatory law edited by Sally Shorthose |
| title_short | Guide to EU and UK pharmaceutical regulatory law |
| title_sort | guide to eu and uk pharmaceutical regulatory law |
| topic | Europäische Union (DE-588)5098525-5 gnd Vergaberecht (DE-588)7574511-2 gnd Regulierung (DE-588)4201190-5 gnd Pharmazeutische Industrie (DE-588)4045696-1 gnd |
| topic_facet | Europäische Union Vergaberecht Regulierung Pharmazeutische Industrie Großbritannien Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034250988&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | UT guidetoeupharmaceuticalregulatorylaw AT shorthosesally guidetoeuandukpharmaceuticalregulatorylaw |