A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial
Abstract Background Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. falciparu...
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ftdoajarticles:oai:doaj.org/article:afed1c50820b48f497a9eb2b6f34ff09 2023-05-15T15:12:08+02:00 A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial Rebecca Pawliw Rebecca Farrow Silvana Sekuloski Helen Jennings Julie Healer Thuan Phuong Pri Sathe Cielo Pasay Krystal Evans Alan F. Cowman Louis Schofield Nanhua Chen James McCarthy Katharine Trenholme 2018-08-01T00:00:00Z https://doi.org/10.1186/s12936-018-2435-x https://doaj.org/article/afed1c50820b48f497a9eb2b6f34ff09 EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2435-x https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2435-x 1475-2875 https://doaj.org/article/afed1c50820b48f497a9eb2b6f34ff09 Malaria Journal, Vol 17, Iss 1, Pp 1-15 (2018) Malaria Plasmodium falciparum Bioreactor In vitro cultivation Good Manufacturing Practice Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2435-x 2022-12-30T21:36:38Z Abstract Background Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. falciparum strains for in vivo use. The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials. Methods Genetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P. falciparum strain 3D7. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. All components used to manufacture the MCB were screened to comply with standards appropriate for in vivo use. The cryopreserved MCB was subjected to extensive testing to ensure GMP compliance for a phase 1 investigational product. Results Two hundred vials of the GAP MCB were successfully manufactured. At harvest, the GAP MCB had a parasitaemia of 6.3%, with 96% of parasites at ring stage. Testing confirmed that all release criteria were met (sterility, absence of viral contaminants and endotoxins, parasite viability following cryopreservation, identity and anti-malarial drug sensitivity of parasites). Conclusion Large-scale in vitro culture of P. falciparum parasites using a wave bioreactor can be achieved under GMP-compliant conditions. This provides a cost-effective methodology for the production of malaria parasites suitable for administration in clinical trials. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic The Knob ENVELOPE(-131.721,-131.721,56.850,56.850) Malaria Journal 17 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Plasmodium falciparum Bioreactor In vitro cultivation Good Manufacturing Practice Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Plasmodium falciparum Bioreactor In vitro cultivation Good Manufacturing Practice Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Rebecca Pawliw Rebecca Farrow Silvana Sekuloski Helen Jennings Julie Healer Thuan Phuong Pri Sathe Cielo Pasay Krystal Evans Alan F. Cowman Louis Schofield Nanhua Chen James McCarthy Katharine Trenholme A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
topic_facet |
Malaria Plasmodium falciparum Bioreactor In vitro cultivation Good Manufacturing Practice Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. falciparum strains for in vivo use. The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials. Methods Genetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P. falciparum strain 3D7. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. All components used to manufacture the MCB were screened to comply with standards appropriate for in vivo use. The cryopreserved MCB was subjected to extensive testing to ensure GMP compliance for a phase 1 investigational product. Results Two hundred vials of the GAP MCB were successfully manufactured. At harvest, the GAP MCB had a parasitaemia of 6.3%, with 96% of parasites at ring stage. Testing confirmed that all release criteria were met (sterility, absence of viral contaminants and endotoxins, parasite viability following cryopreservation, identity and anti-malarial drug sensitivity of parasites). Conclusion Large-scale in vitro culture of P. falciparum parasites using a wave bioreactor can be achieved under GMP-compliant conditions. This provides a cost-effective methodology for the production of malaria parasites suitable for administration in clinical trials. |
format |
Article in Journal/Newspaper |
author |
Rebecca Pawliw Rebecca Farrow Silvana Sekuloski Helen Jennings Julie Healer Thuan Phuong Pri Sathe Cielo Pasay Krystal Evans Alan F. Cowman Louis Schofield Nanhua Chen James McCarthy Katharine Trenholme |
author_facet |
Rebecca Pawliw Rebecca Farrow Silvana Sekuloski Helen Jennings Julie Healer Thuan Phuong Pri Sathe Cielo Pasay Krystal Evans Alan F. Cowman Louis Schofield Nanhua Chen James McCarthy Katharine Trenholme |
author_sort |
Rebecca Pawliw |
title |
A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
title_short |
A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
title_full |
A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
title_fullStr |
A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
title_full_unstemmed |
A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
title_sort |
bioreactor system for the manufacture of a genetically modified plasmodium falciparum blood stage malaria cell bank for use in a clinical trial |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2435-x https://doaj.org/article/afed1c50820b48f497a9eb2b6f34ff09 |
long_lat |
ENVELOPE(-131.721,-131.721,56.850,56.850) |
geographic |
Arctic The Knob |
geographic_facet |
Arctic The Knob |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-15 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2435-x https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2435-x 1475-2875 https://doaj.org/article/afed1c50820b48f497a9eb2b6f34ff09 |
op_doi |
https://doi.org/10.1186/s12936-018-2435-x |
container_title |
Malaria Journal |
container_volume |
17 |
container_issue |
1 |
_version_ |
1766342866198593536 |