determined a collaboration agreement Protalix BioTherapeutics-Pfizer. In addition, it
should be positively noticed that 1-year treatment with taliglucerase allows patients
and national sanitary systems for an estimated cost reduction by 25% with respect to
administration of imiglucerase for the same period. Also the oral route of administration is currently being tested that might reduce discomfort or pain related to
intravenous administration. The results demonstrate that the carrot cells protect the
recombinant protein in the gastric environment and may enable absorption in vitro.
Feeding rats and pigs with carrot cells containing GC proved that active recombinant
enzyme can be found in the digestive tract and blood and can reach the target organs
(Shaaltiel et al. 2015). These results demonstrate that the oral administration of
proteins encapsulated in plant cells is feasible and may be a valuable alternative to
intravenous administration of ERT.
Recombinant canine interferon-alpha (Interberry-alpha) was produced by
Hokusan Co. Ltd. in the National Institute of Advanced Industrial Science and
Technology (NAIST), Hokkaido, Japan. Interberry-alpha is manufactured in genetically modified strawberries in a contained biosafety level 2 facility for transgenic
plants (avoidance of gene release into the environment). This product was approved
for commercialization by the Japanese Ministry of Agriculture, Forestry and Fisheries, and processed strawberries containing were marketed from 2014 for the
treatment of periodontal disease in dogs (Drake et al. 2017).
Production of proteinaceous drugs other than vaccines and antibodies has been
proven in a variety of plant-based expression platforms (from plant cell suspension
cultures to moss, to duckweed) for different applications (Table 7). The advancement status of these products reached phase I and II clinical trial and hopefully can
reach commercial approval.
6 Bringing “Functional” Plants to the Marketplace
6.1 Good Manufacturing Practices
Importantly, and independently from the method used (stable/transient expression),
current EMA regulatory guidelines (EMA 2008) indicate that all biopharmaceutical
products intended for clinical trials should be manufactured according to GMP.
Thus, GMP compliance appears to be a crucial point in developing plant-based
pharmaceuticals for clinical use. In Table 8 the main GMP factories for the production of plant-made biopharmaceuticals are listed. Besides the GMP facility for the
production of the only plant-made therapeutic enzyme approved for human use in
Israel (Protalix/Pfizer), two big facilities are capable of biomanufacturing plantderived pharmaceutical proteins under GMP conditions. Fraunhofer CMB in the
United States deals with regulatory and clinical affairs by managing a GMP pilot
plant equipped with complete processing cycles for transient expression (i.e. plant
farming, bacterial cultures, plant infiltration, biomass harvest and protein purification). Also Medicago Inc., Québec CA, is into clinical trial operating in a similar
facility.
Engineering Plants for the Future: Farming with Value-Added Harvest
91
should be positively noticed that 1-year treatment with taliglucerase allows patients
and national sanitary systems for an estimated cost reduction by 25% with respect to
administration of imiglucerase for the same period. Also the oral route of administration is currently being tested that might reduce discomfort or pain related to
intravenous administration. The results demonstrate that the carrot cells protect the
recombinant protein in the gastric environment and may enable absorption in vitro.
Feeding rats and pigs with carrot cells containing GC proved that active recombinant
enzyme can be found in the digestive tract and blood and can reach the target organs
(Shaaltiel et al. 2015). These results demonstrate that the oral administration of
proteins encapsulated in plant cells is feasible and may be a valuable alternative to
intravenous administration of ERT.
Recombinant canine interferon-alpha (Interberry-alpha) was produced by
Hokusan Co. Ltd. in the National Institute of Advanced Industrial Science and
Technology (NAIST), Hokkaido, Japan. Interberry-alpha is manufactured in genetically modified strawberries in a contained biosafety level 2 facility for transgenic
plants (avoidance of gene release into the environment). This product was approved
for commercialization by the Japanese Ministry of Agriculture, Forestry and Fisheries, and processed strawberries containing were marketed from 2014 for the
treatment of periodontal disease in dogs (Drake et al. 2017).
Production of proteinaceous drugs other than vaccines and antibodies has been
proven in a variety of plant-based expression platforms (from plant cell suspension
cultures to moss, to duckweed) for different applications (Table 7). The advancement status of these products reached phase I and II clinical trial and hopefully can
reach commercial approval.
6 Bringing “Functional” Plants to the Marketplace
6.1 Good Manufacturing Practices
Importantly, and independently from the method used (stable/transient expression),
current EMA regulatory guidelines (EMA 2008) indicate that all biopharmaceutical
products intended for clinical trials should be manufactured according to GMP.
Thus, GMP compliance appears to be a crucial point in developing plant-based
pharmaceuticals for clinical use. In Table 8 the main GMP factories for the production of plant-made biopharmaceuticals are listed. Besides the GMP facility for the
production of the only plant-made therapeutic enzyme approved for human use in
Israel (Protalix/Pfizer), two big facilities are capable of biomanufacturing plantderived pharmaceutical proteins under GMP conditions. Fraunhofer CMB in the
United States deals with regulatory and clinical affairs by managing a GMP pilot
plant equipped with complete processing cycles for transient expression (i.e. plant
farming, bacterial cultures, plant infiltration, biomass harvest and protein purification). Also Medicago Inc., Québec CA, is into clinical trial operating in a similar
facility.
Engineering Plants for the Future: Farming with Value-Added Harvest
91