Rapid development of manufacturing processes for future production of adenovirus-vectored COVID19 vaccine at million-dose scale
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Several COVID-19 vaccine candidates are under development. ‘ChAdOx1 nCoV’, developed at UOXF, is a leading candidate. In clinical trials, other vaccines based upon the same adenovirus technology have proven to be safe and to induce strong immune responses. In monkeys, a vaccine against the MERS virus (which is very similar to COVID-19) achieved protection with a single dose. We will soon be performing clinical trials of ChAdOx1 nCoV, but we need to prepare to manufacture millions of doses of it as soon as possible, in parallel with the clinical trials. This project aims to enable availability of more than 1m doses for clinical use in high-risk groups as soon as possible.
Technical Summary
This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project.
We aim to provide, in <6 months and probably c. 4 months
-A GMP process to produce the University of Oxford’s (UOXF’s) simian adenovirus-vectored COVID-19 vaccine at 200L/ c. 1m-dose scale
-With MHRA engagement, a contingency plan (subject to funding) to make available 1m doses of GMP-like UK-cleanroom-produced material for clinical use as soon as possible.
-Development of options for 1000L-scale (>5m dose) manufacturing in UK & abroad.
Small-batch GMP and clinical trials of the UOXF vaccine are already planned. Supported by the extensive human safety/ immunogenicity record of these vectors, and anticipating supportive primate efficacy/ immunopathology safety data in April, we are contingency planning an emergency clinical trial programme.
With a £0.25m in-kind contribution from PallBiotech, including access to a fully-equipped process development (PD) facility, and starting from our existing GMP 3L-scale process, we are already performing scale-up preparation experiments and anticipate a 50L run at Pall’s facility and then 200L runs as needed, within funds requested here.
With Co-I J Humphreys (VMIC), we are contingency planning near-immediate access to 200L-capable cleanrooms at two CDMOs, both partners in this application (Cobra in Keele, UK & Halix in Leiden NL).
We have requested an emergency meeting with MHRA to discuss regulatory mechanisms to make vaccine available for large-scael use as soon as possible.
We aim to provide, in <6 months and probably c. 4 months
-A GMP process to produce the University of Oxford’s (UOXF’s) simian adenovirus-vectored COVID-19 vaccine at 200L/ c. 1m-dose scale
-With MHRA engagement, a contingency plan (subject to funding) to make available 1m doses of GMP-like UK-cleanroom-produced material for clinical use as soon as possible.
-Development of options for 1000L-scale (>5m dose) manufacturing in UK & abroad.
Small-batch GMP and clinical trials of the UOXF vaccine are already planned. Supported by the extensive human safety/ immunogenicity record of these vectors, and anticipating supportive primate efficacy/ immunopathology safety data in April, we are contingency planning an emergency clinical trial programme.
With a £0.25m in-kind contribution from PallBiotech, including access to a fully-equipped process development (PD) facility, and starting from our existing GMP 3L-scale process, we are already performing scale-up preparation experiments and anticipate a 50L run at Pall’s facility and then 200L runs as needed, within funds requested here.
With Co-I J Humphreys (VMIC), we are contingency planning near-immediate access to 200L-capable cleanrooms at two CDMOs, both partners in this application (Cobra in Keele, UK & Halix in Leiden NL).
We have requested an emergency meeting with MHRA to discuss regulatory mechanisms to make vaccine available for large-scael use as soon as possible.
People |
ORCID iD |
Alexander Douglas (Principal Investigator) |
Publications
Zhang C
(2023)
Lyophilization to enable distribution of ChAdOx1 and ChAdOx2 adenovirus-vectored vaccines without refrigeration.
in NPJ vaccines
Voysey M
(2021)
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
in Lancet (London, England)
Ramasamy MN
(2021)
Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.
in Lancet (London, England)
Folegatti PM
(2020)
Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.
in Lancet (London, England)
Ewer KJ
(2021)
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.
in Nature medicine
Emary K
(2021)
Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)
in SSRN Electronic Journal
Barrett JR
(2021)
Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.
in Nature medicine
Description | COVID-19 vaccine manufacturing |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | The Douglas group developed the original manufacturing process for the Oxford/AstraZeneca COVID-19 vaccine, and supported it's scale up and roll out with AstraZeneca. The foundational work for this was provided by several awards to the Douglas group in recent years. |
Description | Award of contract for the supply of goods & equipment in relation to the ChAdOx1 vaccine development and initial manufacture |
Amount | £12,798,608 (GBP) |
Organisation | Department for Business, Energy & Industrial Strategy |
Sector | Public |
Country | United Kingdom |
Start | 02/2020 |
End | 06/2020 |
Title | Development of manufacturing process for ChAdOx vaccines, applied to the Oxford-AstraZeneca COVID-19 vaccine |
Description | New Upstream and Downstream methods for manufacturing and purifying ChAdOx vaccines at industrial scale. This has been used to make over 2.5billion doses of the Oxford-AZ vaccine (by March 2022) |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | 2.5 billion doses of vaccine to date |
Description | Vaccine manufacturing partnership with VMIC |
Organisation | Vaccines Manufacturing and Innovation Centre (VMIC) |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | VMIC and the Doulgas group collaborated on driving the process development, tech transfer and procurement for the manufacturing of the Oxford/AstraZeneca vaccine |
Collaborator Contribution | VMIC and the Doulgas group collaborated on driving the process development, tech transfer and procurement for the manufacturing of the Oxford/AstraZeneca vaccine |
Impact | The manufacturing of the Oxford/AstraZeneca vaccine is directly attributable to this collaboration. |
Start Year | 2020 |
Description | Vaccine manufacturing process development with PALL |
Organisation | PALL Europe |
Country | United Kingdom |
Sector | Private |
PI Contribution | We provided the initial technical know how and overall drive of the project. |
Collaborator Contribution | PALL provided a facility and expertise for scale up our lab vaccine manufacturing process to the 50L and 200L scale. They provided technical support for tech transfering this process to manufacturing CMOs. They provided loan equipment to enable the process to start quickly at CMOs. |
Impact | The manufacturing of the Oxford/AstraZeneca vaccine can be directly attirbuted to this collaboration. |
Start Year | 2020 |
Title | ChAdOx1 nCoV-19/AZD1222 |
Description | ChAdOx1 nCoV-19, initially supported by VaxHUb, has been in clinical trials in UK, SA, Brazil, Kenya, US, licensed in 60 countries for emergency use |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Wide-scale adoption |
Year Development Stage Completed | 2020 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | Demonstrated unprecedented speed of platform response. |
URL | https://www.isrctn.com/ISRCTN15281137?q=ChAdOx1%20nCoV-19&filters=&sort=&offset=5&totalResults=5&pag... |
Title | Oxford/AstraZeneca COVID-19 vaccine |
Description | Awards to the Douglas group enabled the manufacturing of the Oxford/AstraZeneca vaccine to take place for use in later stage clinical trials. |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Market authorisation |
Year Development Stage Completed | 2021 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | The impact of the Oxford/AstraZeneca COVID-19 have been well documented and are internationally significant. Awards to the Douglas group enabled the development of the manufacturing process required for later stage clinical trials, and global supply of the vaccine. |
Description | COVID-19 vaccine manufacturing press engagment |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Alexander Douglas and Adam Ritchie have both been engaged with the media on the Oxford/AstraZeneca vaccine manufacturing process. This includes: -Appearance on Panarama (BBC, UK) -Quotes/interviews in numerous newspaper and maganzine articles (UK focused) -Radio interviews (including BBC radio 5 (UK) and World Service (international)) |
Year(s) Of Engagement Activity | 2020,2021,2022 |