29 January 2021 EMA/94907/2021 Committee for Medicinal Products for Human Use (CHMP) Assessment report COVID-19 Vaccine AstraZeneca Common name: COVID-19 Vaccine (ChAdOx1-S [recombinant]) Procedure No. EMEA/H/C/005675/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ..................................................................................... 7 1.2. Steps taken for the assessment of the product ........................................................ 9 2. Scientific discussion .............................................................................. 12 2.1. Problem statement ............................................................................................. 12 2.1.1. Disease or condition ........................................................................................ 12 2.1.2. Epidemiology and risk factors ........................................................................... 12 2.1.3. Aetiology and pathogenesis .............................................................................. 12 2.1.4. Clinical presentation and diagnosis .................................................................... 13 2.1.5. Management ................................................................................................... 13 2.2. Quality aspects .................................................................................................. 15 2.2.1. Introduction.................................................................................................... 15 2.2.2. Active substance ............................................................................................. 15 2.2.3. Finished medicinal product ............................................................................... 25 2.2.4. Discussion on chemical, and pharmaceutical aspects ........................................... 35 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 39 2.2.6. Recommendations for future quality development ............................................... 41 2.3. Non-clinical aspects ............................................................................................ 42 2.3.1. Pharmacology ................................................................................................. 42 2.3.2. Pharmacokinetics ............................................................................................ 46 2.3.3. Toxicology ...................................................................................................... 47 2.3.4. Ecotoxicity/environmental risk assessment ......................................................... 49 2.3.5. Discussion on non-clinical aspects ..................................................................... 49 2.3.6. Conclusion on the non-clinical aspects ............................................................... 54 2.4. Clinical aspects .................................................................................................. 54 2.4.1. Introduction.................................................................................................... 54 2.4.2. Pharmacokinetics ............................................................................................ 59 2.4.3. Pharmacodynamics .......................................................................................... 59 2.4.4. Discussion on clinical pharmacology ................................................................... 71 2.4.5. Conclusions on clinical pharmacology ................................................................. 73 2.5. Clinical efficacy .................................................................................................. 73 2.5.1. Main studies ................................................................................................... 74 2.5.2. Pooled efficacy analysis .................................................................................... 77 2.5.3. Discussion on clinical efficacy .......................................................................... 115 2.5.4. Conclusions on clinical efficacy ........................................................................ 123 2.6. Clinical safety .................................................................................................. 124 2.6.1. Methodology ................................................................................................. 124 2.6.2. Patient exposure ........................................................................................... 124 2.6.3. Adverse events ............................................................................................. 125 2.6.4. Serious adverse event/deaths/other significant events ....................................... 135 EMA/94907/2021 Page 2/181 2.6.5. Laboratory findings ........................................................................................ 136 2.6.6. Safety in special populations ........................................................................... 137 2.6.7. Immunological events .................................................................................... 137 2.6.8. Safety related to drug-drug interactions and other interactions ........................... 137 2.6.9. Discontinuation due to adverse events ............................................................. 138 2.6.10. Post marketing experience ............................................................................ 138 2.6.11. Discussion on clinical safety .......................................................................... 138 2.6.12. Conclusions on the clinical safety ................................................................... 141 2.7. Risk Management Plan ...................................................................................... 142 2.7.1. Safety concerns ............................................................................................ 142 2.7.2. Pharmacovigilance plan .................................................................................. 144 2.7.3. Risk minimisation measures............................................................................ 154 Routine Risk Minimisation Measures .......................................................................... 154 Summary of additional risk minimisation measures ..................................................... 154 2.8. Pharmacovigilance ........................................................................................... 157 2.8.1. Pharmacovigilance system .............................................................................. 157 2.8.2. Periodic Safety Update Reports submission requirements ................................... 158 2.9. New Active Substance ...................................................................................... 158 2.10. Product information ........................................................................................ 158 2.10.1. User consultation ......................................................................................... 158 2.10.2. Labelling exemptions ................................................................................... 158 2.10.3. Quick Response (QR) code ............................................................................ 161 2.10.4. Additional monitoring ................................................................................... 161 2.11. Compliance with scientific advice ...................................................................... 161 3. Benefit-Risk Balance ........................................................................... 162 3.1.1. Disease ........................................................................................................ 162 3.1.2. Available therapies and unmet medical need ..................................................... 162 3.1.3. Main clinical studies ....................................................................................... 162 3.2. Favourable effects ............................................................................................ 163 3.3. Uncertainties and limitations about favourable effects ........................................... 164 3.4. Unfavourable effects ......................................................................................... 166 3.5. Uncertainties and limitations about unfavourable effects ....................................... 168 3.6. Effects Table .................................................................................................... 169 3.7. Benefit-risk assessment and discussion ............................................................... 171 3.7.1. Importance of favourable and unfavourable effects ............................................ 171 3.7.2. Balance of benefits and risks .......................................................................... 172 3.7.3. Additional considerations on the benefit-risk balance ........................................