19 February 2021 EMA/707383/2020 Corr.1*1 Committee for Medicinal Products for Human Use (CHMP) Assessment report Comirnaty Common name: COVID-19 mRNA vaccine (nucleoside-modified) Procedure No. EMEA/H/C/005735/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 1 * Correction dated 19 February 2021 to clarify ERA statement 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 An agency of the European Union Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 8 1.1. Submission of the dossier ...................................................................................... 8 1.2. Steps taken for the assessment of the product ......................................................... 9 2. Scientific discussion .............................................................................. 11 2.1. Problem statement ............................................................................................. 11 2.1.1. Disease or condition ......................................................................................... 11 2.1.2. Epidemiology and risk factors ............................................................................ 11 2.1.3. Aetiology and pathogenesis .............................................................................. 11 2.1.4. Clinical presentation and diagnosis .................................................................... 12 2.1.5. Management ................................................................................................... 13 2.2. Quality aspects .................................................................................................. 14 2.2.1. Introduction .................................................................................................... 14 2.2.2. Active Substance ............................................................................................. 15 2.2.3. Finished Medicinal Product ................................................................................ 22 2.2.4. Discussion on chemical, pharmaceutical and biological aspects .............................. 31 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 35 2.2.6. Recommendations for future quality development................................................ 39 2.3. Non-clinical aspects ............................................................................................ 41 2.3.1. Pharmacology ................................................................................................. 41 2.3.2. Pharmacokinetics............................................................................................. 45 2.3.3. Toxicology ...................................................................................................... 48 2.3.4. Ecotoxicity/environmental risk assessment ......................................................... 51 2.3.5. Discussion on non-clinical aspects...................................................................... 51 2.3.6. Conclusion on the non-clinical aspects ................................................................ 55 2.4. Clinical aspects .................................................................................................. 56 2.4.1. Introduction .................................................................................................... 56 2.4.2. Pharmacokinetics............................................................................................. 58 2.4.3. Pharmacodynamics .......................................................................................... 58 2.4.4. Discussion on clinical pharmacology ................................................................... 66 2.4.5. Conclusions on clinical pharmacology ................................................................. 67 2.5. Clinical efficacy .................................................................................................. 67 2.5.1. Dose response study ........................................................................................ 67 2.5.2. Main study ...................................................................................................... 67 2.5.3. Discussion on clinical efficacy ............................................................................ 92 2.5.4. Conclusions on clinical efficacy .......................................................................... 97 2.6. Clinical safety .................................................................................................... 98 2.6.1. Patient exposure ............................................................................................. 99 2.6.2. Reactogenicity ............................................................................................... 101 2.6.3. Adverse events ............................................................................................. 103 2.6.4. Serious adverse event/deaths/other significant events ....................................... 108 2.6.5. Laboratory findings ........................................................................................ 109 2.6.6. Safety in special populations ........................................................................... 109 2.6.7. Safety related to drug-drug interactions and other interactions ........................... 110 Assessment report EMA/707383/2020 Page 2/140 2.6.8. Discontinuation due to adverse events ............................................................. 110 2.6.9. Post marketing experience .............................................................................. 110 2.6.10. Discussion on clinical safety .......................................................................... 111 2.6.11. Conclusions on the clinical safety ................................................................... 114 2.7. Risk Management Plan ...................................................................................... 115 Safety Specification ................................................................................................. 115 Pharmacovigilance Plan ........................................................................................... 116 Routine pharmacovigilance activities ......................................................................... 116 Additional pharmacovigilance activities ...................................................................... 118 Overall conclusions on the Pharmacovigilance Plan ...................................................... 122 Plans for post-authorisation efficacy studies ............................................................... 122 Risk minimisation measures ..................................................................................... 123 Routine Risk Minimisation Measures .......................................................................... 123 Summary of additional risk minimisation measures ..................................................... 123 Overall conclusions on risk minimisation measures ...................................................... 126 Summary of the risk management plan ..................................................................... 127 Conclusion on the RMP ............................................................................................ 127 2.8. Pharmacovigilance ............................................................................................ 127 2.9. Product information .......................................................................................... 127 2.9.1. User consultation ........................................................................................... 127 2.9.2. Labelling exemptions ..................................................................................... 127 2.9.3. Quick Response (QR) code .............................................................................. 129 2.9.4. Additional monitoring ..................................................................................... 129 3. Benefit-Risk Balance............................................................................ 130 3.1. Therapeutic Context ......................................................................................... 130 3.1.1. Disease or condition ....................................................................................... 130 3.1.2. Available therapies and unmet medical need ..................................................... 130 3.1.3. Main clinical studies ....................................................................................... 130 3.2. Favourable effects ............................................................................................ 131 3.3. Uncertainties and limitations about favourable effects ........................................... 132 3.4. Unfavourable effects ......................................................................................... 132 3.5. Uncertainties and limitations about unfavourable effects ....................................... 133 3.6. Effects Table ...................................................................................................