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New Form of Human Recombinant Erythropoietin

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Development of Technology of Producing Tablet Formulation of Human Recombinant Erythropoietin for Oral Administration

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-CHM/Biochemistry/Biotechnology
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
27.02.2003

Leading Institute
State Research Center of Virology and Biotechnology VECTOR, Russia, Novosibirsk reg., Koltsovo

Collaborators

  • Technology Development Company / Moscow Representative Office, Russia, Moscow\nDépartement d'immunologie / Laboratoire National de Santé / WHO Collaborating Center for Measles, Luxembourg, Luxembourg\nRoyal Knight Inc., USA, MN, Rochester

Project summary

Erythropoietin (EPO) is a glycoprotein hormone that stimulates erythrocyte secretion in human blood. At present, EPO is regarded as an effective medication for treating patients with anemia caused by renal insufficiency, arthritis, or those with side-effects as a result of treatment for AIDS with azidothymidine (AZT) or other medicines. Such patients need frequent blood transfusions or EPO hormone injections. Since during transfusion and injections there is a danger of transferring infectious agents, an oral formulation of EPO would make treatment safer and more effective.

For the time being, the injection formulation of recombinant human EPO (r-hEPO) is produced by foreign companies «Amgen» (USA), «Celltech» (Great Britain), «Kirin» (Japan). Neither abroad nor in Russia are there dosage oral forms of this drug.

Medical demand for EPO is rather high: a week’s dose for maintaining the necessary hemoglobin levels in blood is 2,800-6,720 units in hypodermic administration of the drug and 8,350-20,300 units when it is administered intravenously (Bommer J., Ritz E., et al., 1988). High demand for preparations of the recombinant hormone (the number of consumers in Russia is estimated at hundreds of thousands of people) and high costs of the treatment course (American company Amgen sells its EPO dosage form at $10 per 1,000 units) contribute to a significant commercial value of the proposed technology.

The goal of the present project is to develop technology for manufacturing a new formulation of recombinant human erythropoietin (r-hEPO) for oral administration.

Current situation at SRC VB VECTOR creates good opportunities for a successful implementation of the project. A new highly productive strain of the CHOpE cell culture producing r-hEPO has been derived by genetic and cellular engineering. VECTOR specialists have carried out laboratory studies on extraction, concentration, purification and certification of experimental samples of the bulk substance of r-hEPO. Experimental batches of a tablet formulation of the drug have been produced. In animal experiments, this tablet formulation of r-hEPO has been demonstrated to have specific activity. Work has been started to investigate this preparation in preclinical studies. Considering the above-said, we propose to carry out studies to develop technology of a new drug formulation of r-hEPO for oral use, including complete certification of the molecular and biological properties of the strain of a cell culture producing r-hEPO and stability studies; preparation and control of the semi-finished product; selection of purification conditions and total control of the bulk substance of r-hEPO; lyophilization and tableting; producing experimental batches of the drug and testing these in animals and human volunteers.

It is proposed to implement the project in two stages. During the first year, it is proposed to prepare and certify an experimental batch of the table formulation of r-hEPO to be tested in human volunteers to explore the need to conduct further studies aimed at the development of technology of the novel drug formulation. During the 2nd and 3rd years, it is proposed to refine technology of the tablet formulation of r-hEPO for oral use, including characterization and stability studies on the producer strain; bringing the purification process up to international standards; refining the conditions of stabilization of the purified product; tableting; development of scientific and technical documentation, and carrying out drug trials.

To carry out the project, highly trained scientific and technical personnel of three departments will be involved that have many years of experience in genetic construction and recombinant drug design.

As a result of the project, data would be obtained that would make it possible to develop approaches to new technology (not only in Russia) of r-hEPO for oral use, create a new formulation of a genetically engineered hormonal drug, which would significantly facilitate and make less expensive the schemes of treatment of patients with erythropoiesis disorders. This project would open up new opportunities for practical health care in Russia and abroad and identify new promising directions of scientific research. A commercial value will be generated by new technology of the tablet formulation of r-hEPO. Based on this technology, other new formulations of recombinant products could be developed to allow a directed delivery to target organs. The spectrum of diseases with erythropoiesis disorders treatable with this drug would be extended and new therapy schemes developed, which is of great scientific and practical interest to public health not only in Russia but also abroad.

Today similar research is being conducted by companies LEK (Slovenia) and Schein Pharmaceutical (USA) that could be collaborators in this proposed research. Final stages of the year 1 activities – limited trials of the tablet formulation of r-hEPO in human volunteers – will be carried out in collaboration with specialists of a US company: Schein Pharmaceutical. If the project is carried out, it will make it possible to involve a large number of scientists (formerly involved in biological defense) issues in international collaborative activities aimed at developing novel genetically engineered products. These scientists will have an opportunity to utilize their scientific and professional expertise to solve current public health challenges, which is critical not only to Russia but also to the world’s scientific community. The involvement of VECTOR staff would also help solve an important social problem of their reorientation, which is consistent with ISTC’s goals and objectives.


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ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.

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