Product Development Plasma Products
Contact person: Anky Koenderman PhD
The product development strategy of the division Plasma Products aims primarily at maintaining the state-of-the-art level of its plasma derivatives portfolio and production processes. To that end, the product and process development program is regularly evaluated and updated if needed. Besides, opportunities for development of new (plasma) products are being explored in feasibility studies which may evolve into full-blown development projects when considered to be economically feasible.
- Development of new products
- Improvement of plasma products
- Characterization/new indications
- Key publications
Holotransferrin and Apotransferrin
Project leaders: H. ter Hart and I. Prins
Development of a manufacturing process for transferrin has been realized in close collaboration with L. von Bonsdorff, Sanquin Oy, Finland. Transferrin is produced in two forms: the iron-free form, apotransferrin, and the iron-saturated form, holotransferrin. Apotransferrin is now evaluated in a clinical study in patients with hypotransferrinemia and has received a European orphan drug designation for this indication. Holotransferrin can be used as a drug targeting agent in the treatment of certain cancers as is currently investigated by the Japanese company Mebiopharm, and also as a growth promoting agent in cell culturing.
Project leader: G.J. Derksen
A project to develop a second, intermediate pure, FVIII/vWF product besides Aafact in close collaboration with the D&R group at CAF-DCF (Brussels, Belgium) is ongoing. To guarantee virus and prion safety, three pathogen reducing steps were developed and implemented in the manufacturing process: SD-treatment, UVC and dry-heat treatment. Large scale manufacturing of this FVIII/vWF product for characterization purposes, virus validation studies and pre-clinical studies are ongoing. Pre-clinical and clinical studies are planned.
Development of new formulations
Project leaders: A. Koenderman and I. Prins
Cetor®, a high-purity C1-inhibitor product and Cinryze™, C1-Inhibitor product manufactured from USA plasma, are used for the treatment of hereditary angioedema (HAE). For both products studies are started to develop a new formulation for subcutaneous administration in close collaboration with partners in the USA.
Virus and prion safety of plasma products
Project leaders: H. ter Hart and I. Prins
To update the virus and prion safety of several plasma products, the use of new virus removal filters was studied in feasibility studies. It was shown that a new filter can be implemented in several manufacturing processes (a.o. Nanogam®, GammaQuin® and Cofact®) to obtain state-of-the-art virus removal. This new filter was implemented in the Nanogam® manufacturing process and will be implemented in the Cofact® manufacturing process.
Project leader: A Koenderman
In collaboration with the Dept of Immunopathology, studies on IgG products are ongoing to study dimer formation and polymerization of IgG and its significance in the occurrence of adverse events in patients and the role of glycosylation of IgG for its biological activity.
To improve the use of plasma products characterization studies were started to further characterize Sanquin’s current products Cofact®, Aafact®, Nanogam® and Cetor®/Cinryze™ and the experimental products Holotransferrin and Apotransferrin. Also studies were started to characterize IgG products for the presence/absence of procoagulant activity.
To develop new indications for Cetor® collaborations were started with research groups of the University Medical Center Utrecht and the Radboud University Nijmegen Medical Center.
Up to now there is no efficacious treatment available for severely affected trauma patients. A human LPS model has been used to mimic the cytokine response of trauma patients and to study a possible role of C1-Inhibitor on the cytokine response. The ’VECTOR Study‘ (In vivo effects of C1-esterase inhibitor on innate immune response during endotoxemia in human) was performed. It was shown that C1-Inhibitor reduces the pro-inflammatory cytokines and increases the anti-inflammatory cytokines studied. To further study the effect of C1-Inhibitor on systemic inflammation in trauma patients, the CAESAR study was designed. This study will start in 2012.
- Heeres M, Visser T, van Wessem KJ, Koenderman AH, Strengers PF, Koenderman L, Leenen LP. The effect of C1-esterase inhibitor on systemic inflammation in trauma patients with a femur fracture - The CAESAR study: study protocol for a randomized controlled trial. Trials 2011; 12:223.
- Guhr T, Bloem J, Derksen NI, Wuhrer M, Koenderman AH, Aalberse RC, Rispens T. Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia. PLoS One. 2011; 6(6):e21246.