1.1. Submission of the dossier
The applicant AstraZeneca AB submitted on 11 January 2021 an application for marketing authorisation to the European Medicines Agency (EMA) for COVID-19 Vaccine AstraZeneca, through the centralised procedure falling within the Article 3(1) and point 1 of Annex of Regulation (EC) No 726/2004. The eligibility to the centralised procedure was agreed upon by the EMA/CHMP on 9 June 2020.
The applicant applied for the following indication:
“COVID-19 Vaccine AstraZeneca is indicated for active immunisation to prevent COVID 19 caused by SARS-CoV-2, in individuals 18 years of age and older.
The use of this vaccine should be in accordance with official recommendations”.
The legal basis for this application refers to:
Article 8.3 of Directive 2001/83/EC - complete and independent application
The application submitted is composed of administrative information, complete quality data, non-clinical and clinical data based on applicants’ own tests and studies and/or bibliographic literature substituting/supporting certain tests or studies.
Information on Paediatric requirements
Pursuant to Article 7 of Regulation (EC) No 1901/2006, the application included an EMA Decision P/0003/2021 on the agreement of a paediatric investigation plan (PIP).
At the time of submission of the application, the PIP P/0003/2021 was not yet completed as some measures were deferred.
Information relating to orphan market exclusivity
Similarity
Pursuant to Article 8 of Regulation (EC) No. 141/2000 and Article 3 of Commission Regulation (EC) No 847/2000, the applicant did not submit a critical report addressing the possible similarity with authorised orphan medicinal products because there is no authorised orphan medicinal product for a condition related to the proposed indication.
Applicant’s requests for consideration
Conditional marketing authorisation
accordance with Article 14-a of the Regulation (EC) No 726/2004.
New active Substance status
The applicant requested the active substance Chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (ChAdOx1-S)contained in the above medicinal product to be considered as a new active
substance, as the applicant claims that it is not a constituent of a medicinal product previously authorised within the European Union.
Scientific advice
The applicant received the following Scientific advices on the development relevant for the indication subject to the present application:
Date Reference SAWP co-ordinators
11 September 2020 EMEA/H/SA/4655/1/2020/II Ms Rosalia Ruano Camps and Prof Brigitte Schwarzer-Daum
16 September 2020 EMEA/H/SA/4655/3/2020/I Ms Rosalia Ruano Camps and Dr Karin Janssen van Door
18 September 2020 EMEA/H/SA/4655/2/2020/I Ms Rosalia Ruano Camps and Prof Brigitte Schwarzer-Daum
27 October 2020 EMEA/H/SA/4690/1/2020/II Dr Jens Reinhardt and Dr Ingrid Schellens
28 October 2020 EMEA/H/SA/4655/1/FU/1/2020/II Dr Ferran Torres and Dr Ingrid Schellens
The Scientific advice pertained to the following quality, non-clinical, and clinical aspects:
• Concurrent and prospective process validation approach
• Proposal, after MAA, to release batches for distribution made prior to the initiation of validation, provided that pre-PV lots will demonstrate alignment with the commercial process and meet the approved commercial specifications
• Proposed use of a rapid method for sterility testing as an alternative to Ph. Eur. 2.6.1
• Preclinical vector biodistribution studies
• DART studies
• Concurrence that juvenile animal studies are not needed
• Provision of published data instead of preclinical studies reports to support regulatory submission
• Concurrence that supportive platform information gathered from previous early-phase clinical studies of the vaccine vector in support of the registration of AZD1222 will be submitted in the format of scientific journals
• The proposed immunogenicity objectives and the assay methodologies, and validation status
• Proposed strategy using pooled efficacy, immunogenicity, and safety data from across the UK Phase I/II Study COV001, UK Phase II/III Study COV002, Brazil Phase III Study COV003, and South Africa
Phase I/II Study COV005 to support regulatory submission
• Sufficiency of data from interim analyses for regulatory decision
• Statistical analysis plan
• Acceptability of pooled datasets from HD/HD and from LD/HD under the condition that immunogenicity is similar across various subsets
• Risk management plan
• Signal detection strategy
COVID-19 EMA pandemic Task Force (COVID-ETF)
In line with their mandate as per the EMA Emerging Health Threats Plan, the ETF undertook the following activities in the context of this marketing authorisation application:
The ETF endorsed the Scientific Advice letter, confirmed eligibility to the rolling review procedure based on the information provided by the applicant and agreed the start of the rolling review procedure.
Furthermore, the ETF discussed the (Co-)Rapporteur’s assessment reports overviews and provided their recommendation to the CHMP in preparation of the written adoption rolling review procedures. The corresponding interim opinions were subsequently adopted by the CHMP.
For the exact steps taken at ETF, please refer to section 1.2.
1.2. Steps taken for the assessment of the product
The Rapporteur and Co-Rapporteur appointed by the CHMP were:
Rapporteur: Sol Ruiz Co-Rapporteur: Johann Lodewijk Hillege
The CHMP confirmed eligibility to the centralised procedure on 09 June 2020 The ETF recommended to start the rolling review procedure on 22 September 2020 The applicant submitted documentation as part of a rolling review on
non-clinical data to support the marketing authorisation application 30 September 2020 The procedure (Rolling Review 1) started on 01 October 2020 The Rapporteur's first Assessment Report was circulated to all CHMP,
Peer Reviewer and ETF on 15 October 2020
The Rapporteurs circulated updated Joint Assessment reports to all
CHMP, Peer Reviewer and ETF on 27 October 2020
ETF discussions took place on 29 October 2020
Adoption of first Interim Opinion (Rolling Review 1) via 24 hour written
procedure on 06 November 2020
The applicant submitted documentation as part of a rolling review 2 on non-clinical and quality data to support the marketing authorisation
application 11 December 2020
The procedure (Rolling Review 2) started on 12 December 2020 The applicant submitted documentation as part of a rolling review
(Rolling Review 3) on clinical data (clinical and RMP) to support the
marketing authorisation application 24 December 2020
The procedure (Rolling Review 3) started on 24 December 2020 The Rapporteurs circulated ERA Joint Assessment reports to all CHMP,
Peer Reviewer and ETF on 28 December 2020
ETF discussions took place on 07 January 2021
Adoption of second Interim Opinion (Rolling Reviews 2 and 3) via 24
hour written procedure on 09 January 2021
The application for the conditional marketing authorisation was formally
received by the EMA on 11 January 2021
The procedure started on 12 January 2021
The following GMP inspections were requested by the CHMP and their outcome taken into consideration as part of the Quality/Safety/Efficacy assessment of the product: 1. ‘Catalent Maryland Harmans (BWI),7555, Harmans Road, Harmans, Maryland 21077, USA’ proposed as drug substance manufacture and 2. ‘Catalent Località Fontana del Ceraso, S.P. Casilina 12 n. 41, 03012 Anagni FR, Italy’ proposed as drug product manufacture and QC testing site.
1. 14-17 December 2020 2. 30 November - 03 December 2020
BWP extraordinary adobe meeting was held on 13 January 2021 The CHMP rapporteur's and co-rapporteurs Assessment Reports were
circulated to all CHMP, PRAC, BWP, peer reviewer and ETF on 18 January 2021 The PRAC rapporteur's Assessment Report was circulated to all CHMP,
PRAC and ETF on 18 January 2021
BWP meeting was held on 19 January 2021
ETF discussions took place on 21 January 2021
BWP extraordinary meeting was held on 22 January 2021
The PRAC agreed on the PRAC Assessment Overview and Advice to
CHMP during an extraordinary PRAC meeting on 22 January 2021
ETF discussions took place on 22 January 2021
The outstanding issues were addressed by the applicant during an oral
explanation before the CHMP during the meeting on 26 January 2021
The CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, issued a positive opinion for granting a conditional marketing authorisation to COVID-19 Vaccine AstraZeneca
during the CHMP meeting on 29 January 2021