Periodic Reporting for period 3 - EBOMAN (Manufacturing and Development for Rapid Access Ebola Vaccine (EBOMAN) – Sofia ref.: 115850)
Okres sprawozdawczy: 2017-01-01 do 2017-11-30
This Action (Topic 2: Manufacturing Capability) forms part of an integrated programme to address the urgent unmet needs of accelerating the development of an Ebola vaccine.
This Action supported the overall Ebola+ programme goals by focusing on:
* The development and manufacture of sufficient GMP grade Clinical Trial Materials of Ad26.ZEBOV and MVA-BN(r)-Filo vectored vaccines to support EBOVAC 1 and EBOVAC2 clinical development.
* The scaling up of production processes such that large quantities of vaccine could be manufactured and made available if the Ebola outbreak remained unchecked and international bodies such as the WHO and GAVI recommended rapid deployment of the current vaccine candidates.
* The development of a BSL-2 fill & finish capacity to allow for manufactured bulk drug substance to be filled into vials ready for vaccine deployment as final drug product.
In parallel, work was initiated to generate data to facilitate discussions with regulatory bodies to potentially allow for reclassification of the drug substance as BSL-1, opening up significant additional Fill & Finish capacity that was a bottleneck for the supply of large quantities of Ebola vaccine.
The main objectives of this Action were to manufacture sufficient supplies (and overages) for the clinical studies described in EBOVAC 1 and EBOVAC 2 and to prepare for a potential rapid access to large quantities of Ad26.ZEBOV (prime) and MVA-BN(r)-Filo (boost) vaccine in case of further escalation of the Ebola outbreak
The program therefore covered immediate manufacturing of clinical material and creation of additional capacity (by means of preparation for scale up and process improvements) and product understanding (BSL classification downgrading, process and product characterisation) to cope with increased need for the vaccine.
The program included:
* Manufacturing, release and supply of Ad26.ZEBOV and MVA-BN(r)-Filo vaccine candidate for clinical studies as described in EBOVAC 1 and EBOVAC 2.
* Process development activities required to enable possible scale up of Ad26.ZEBOV manufacturing to 50L and the 300L scale for MVA-BN(r)-Filo production.
* Execution of process development activities to ensure scale up of Ad26.ZEBOV and MVA-BN(r)-Filo to support potential manufacturing of up to 4M doses.
* Generation of material for further stability investigations towards late phase
* Generation of data to support the possibility of downgrading of product handling from Biosafety level 2 to level 1.
* Building of additional BSL2 capacity supporting requirements for larger quantities of Drug Product
Process and product understanding to support Phase II and III clinical trial applications
This Action supported the overall Ebola+ programme goals by focusing on:
* The development and manufacture of sufficient GMP grade Clinical Trial Materials of Ad26.ZEBOV and MVA-BN(r)-Filo vectored vaccines to support EBOVAC 1 and EBOVAC2 clinical development.
* The scaling up of production processes such that large quantities of vaccine could be manufactured and made available if the Ebola outbreak remained unchecked and international bodies such as the WHO and GAVI recommended rapid deployment of the current vaccine candidates.
* The development of a BSL-2 fill & finish capacity to allow for manufactured bulk drug substance to be filled into vials ready for vaccine deployment as final drug product.
In parallel, work was initiated to generate data to facilitate discussions with regulatory bodies to potentially allow for reclassification of the drug substance as BSL-1, opening up significant additional Fill & Finish capacity that was a bottleneck for the supply of large quantities of Ebola vaccine.
The main objectives of this Action were to manufacture sufficient supplies (and overages) for the clinical studies described in EBOVAC 1 and EBOVAC 2 and to prepare for a potential rapid access to large quantities of Ad26.ZEBOV (prime) and MVA-BN(r)-Filo (boost) vaccine in case of further escalation of the Ebola outbreak
The program therefore covered immediate manufacturing of clinical material and creation of additional capacity (by means of preparation for scale up and process improvements) and product understanding (BSL classification downgrading, process and product characterisation) to cope with increased need for the vaccine.
The program included:
* Manufacturing, release and supply of Ad26.ZEBOV and MVA-BN(r)-Filo vaccine candidate for clinical studies as described in EBOVAC 1 and EBOVAC 2.
* Process development activities required to enable possible scale up of Ad26.ZEBOV manufacturing to 50L and the 300L scale for MVA-BN(r)-Filo production.
* Execution of process development activities to ensure scale up of Ad26.ZEBOV and MVA-BN(r)-Filo to support potential manufacturing of up to 4M doses.
* Generation of material for further stability investigations towards late phase
* Generation of data to support the possibility of downgrading of product handling from Biosafety level 2 to level 1.
* Building of additional BSL2 capacity supporting requirements for larger quantities of Drug Product
Process and product understanding to support Phase II and III clinical trial applications
In Year 1 sufficient supplies of Ad26.ZEBOV and MVA-BN-Filo have been manufactured and released to the clinical program covered under EBOVAC 1 and 2, including any Health Authority submission packages (CMC).
Vialed product has been manufactured in excess (>1M vials of both Ad26.ZEBOV and MVA.BN.Filo) that can be rapidly accessed for any emergency needs.
Capacity is being made available for further manufacturing.
Meanwhile further improvements of process understanding and optimization did start and continued in Year 2.
In Year 2 focus was on completing activities on Ad26.ZEBOV and MVA-BN-Filo covered under this grant in addition to applying for Emergency Use Assessment Listing (EUAL).
Capacity increase for filling was progressed for completion in Year 3.
With sufficient supplies in stock, EBOMAN has continued to deliver clinical material for studies run under EBOVAC 1 and 2.
During year 3, the main focus was on completing task 4.3 "Fill & Finish capacity extension", a primary task of Vibalogics.
This included some tests and modifications concerning the new fill and finish line: preliminary work concerning the expected supply and implementation of the labelling machine, followed by the delivery, implementation, validation and qualification of the labelling machine.
To close out Work Package 2, A summary report covering the studies performed under Task 2.6 (MVA-BN(r)-Filo Drug Substance - Manufacturing Process Development and transfer) was finalised and submitted.
It was concluded that current process parameter settings were shown to be adequate for processing of MVA-BN(r) Filo and therefore no changes were introduced to the large-scale process.
Under Task 2.8 (MVA-BN(r)-Filo Drug Substance Product characterization and comparability) the summary report was submitted.
The comparability report (Comparability and Characterization of MVA- BN(r)-Filo Bulk Drug Substance) s ummarized the results from characterization of the MVA-BN(r)-Filo
Bulk Drug Substance (BDS) batches manufactured at Bavarian Nordic A/S and Final Drug Product (FDP) batches manufactured at IDT Biologika GmbH (IDT), Dessau, Germany.
The characterization analysis was performed to gain additional knowledge of the product moving forward in clinical trials and to support future comparability assessments of the MVA-BN(r)-Filo BDS.
Vialed product has been manufactured in excess (>1M vials of both Ad26.ZEBOV and MVA.BN.Filo) that can be rapidly accessed for any emergency needs.
Capacity is being made available for further manufacturing.
Meanwhile further improvements of process understanding and optimization did start and continued in Year 2.
In Year 2 focus was on completing activities on Ad26.ZEBOV and MVA-BN-Filo covered under this grant in addition to applying for Emergency Use Assessment Listing (EUAL).
Capacity increase for filling was progressed for completion in Year 3.
With sufficient supplies in stock, EBOMAN has continued to deliver clinical material for studies run under EBOVAC 1 and 2.
During year 3, the main focus was on completing task 4.3 "Fill & Finish capacity extension", a primary task of Vibalogics.
This included some tests and modifications concerning the new fill and finish line: preliminary work concerning the expected supply and implementation of the labelling machine, followed by the delivery, implementation, validation and qualification of the labelling machine.
To close out Work Package 2, A summary report covering the studies performed under Task 2.6 (MVA-BN(r)-Filo Drug Substance - Manufacturing Process Development and transfer) was finalised and submitted.
It was concluded that current process parameter settings were shown to be adequate for processing of MVA-BN(r) Filo and therefore no changes were introduced to the large-scale process.
Under Task 2.8 (MVA-BN(r)-Filo Drug Substance Product characterization and comparability) the summary report was submitted.
The comparability report (Comparability and Characterization of MVA- BN(r)-Filo Bulk Drug Substance) s ummarized the results from characterization of the MVA-BN(r)-Filo
Bulk Drug Substance (BDS) batches manufactured at Bavarian Nordic A/S and Final Drug Product (FDP) batches manufactured at IDT Biologika GmbH (IDT), Dessau, Germany.
The characterization analysis was performed to gain additional knowledge of the product moving forward in clinical trials and to support future comparability assessments of the MVA-BN(r)-Filo BDS.
The EBOMAN project covers the development of a manufacturing process for a vaccine candidate and it is not a research project seeking to go beyond the state of art.
The priority for the EBOMAN consortium was the acceleration of the vaccine development and GMP manufacturing process.
From this aspect, the project has gone beyond the state of art, performing the development process usually lasting about 8 years within 2 years.
This significant acceleration was not achieved by technological advances but by taking substantial risks, leveraging platform data for both components and performing multiple activities in parallel.
Furthermore, additional capacity was created and scenarios rehearsed, allowing a more flexible and rapid response to emergency need.
The priority for the EBOMAN consortium was the acceleration of the vaccine development and GMP manufacturing process.
From this aspect, the project has gone beyond the state of art, performing the development process usually lasting about 8 years within 2 years.
This significant acceleration was not achieved by technological advances but by taking substantial risks, leveraging platform data for both components and performing multiple activities in parallel.
Furthermore, additional capacity was created and scenarios rehearsed, allowing a more flexible and rapid response to emergency need.