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dc.contributor.authorMa, Julian K-C.
dc.contributor.authorDrossard, Jürgen
dc.contributor.authorLewis, David
dc.contributor.authorAltmann, Friedrich
dc.contributor.authorBoyle, Julia
dc.contributor.authorChristou, Paul
dc.contributor.authorCole, Tom
dc.contributor.authorDale, Philip
dc.contributor.authorvan Dolleweerd, Craig J.
dc.contributor.authorIsitt, Valerie
dc.contributor.authorKatinger, Dietmar
dc.contributor.authorLobedan, Martin
dc.contributor.authorMertens, Hubert
dc.contributor.authorPaul, Mathew J.
dc.contributor.authorRademacher, Thomas
dc.contributor.authorSack, Markus
dc.contributor.authorHundleby, Penelope A. C.
dc.contributor.authorStiegler, Gabriela
dc.contributor.authorStöger, Eva
dc.contributor.authorTwyman, Richard M.
dc.contributor.authorVcelar, Brigitta
dc.contributor.authorFischer, Rainer
dc.date.accessioned2016-12-20T11:49:13Z
dc.date.available2016-12-20T11:49:13Z
dc.date.issued2015
dc.identifier.issn1467-7644
dc.identifier.urihttp://hdl.handle.net/10459.1/58877
dc.description.abstractAlthough plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins.ca_ES
dc.description.sponsorshipThe authors acknowledge funding from the European Union for the Pharma-Planta project (LSHB-CT-2003-503565) as well as additional funding for related and follow-on projects including CoMoFarm (227420), the COST Action Molecular Farming (FA0804), the Grand Challenges in Global Health and the Wellcome Trust (37872) and the ERC advanced grant FuturePharma (269110). We also would like to thank Fraunhofer Gesellschaft for strategic funding.ca_ES
dc.language.isoengca_ES
dc.publisherWileyca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1111/pbi.12416ca_ES
dc.relation.ispartofPlant Biotechnology Journal, 2015, vol. 13, núm.8, p. 1106-1120ca_ES
dc.rights(c) Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd, 2015ca_ES
dc.subjectMonoclonal antibodyca_ES
dc.subjectTransgenic plantsca_ES
dc.subjectTobaccoca_ES
dc.subjectPhase Ica_ES
dc.titleRegulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plantsca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1111/pbi.12416
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/227420
dc.date.embargoEndDate2025-01-01


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