Masterstudiengang "Drug Regulatory Affairs"


Regulatory requirements in Europe for the development of active pharmaceutical ingredients derived from transgenic plants ***

Dr. Daniel Schwarz (Abschlußjahr: 2005)

Language: English

At present biopharmaceuticals are manufactured exclusively in bacteria, yeast cells and mammalian cells. The production possibilities in plants could be shown several times in the meantime. The advantages of “Molecular Pharming” regarding fast up-scalings of the production and the smaller investment aroused interest with biotech companies as well as several pharmaceutical companies.

Decisions about expensive fermenter installations must be made in a phase, in which it is neither to be foreseen whether a product development fails still in clinical testing or will serve enormous markets on a long-term basis.

Therefore, alternative technologies are used for the expression of biopharmaceuticals, some of them also at lower costs. One such alternative is the creation of transgenic animals (“pharming”), but this suffers from the disadvantage that it requires a long time to establish such animals (approximately 2 years). Ethical debates sometimes arise from the use of transgenic animal for production of biopharmaceuticals.

Plants have been a source of medicinal products throughout human evolution. These active pharmaceutical compounds have been primarily small molecules, however.

Advances in genetic engineering are now allowing for the production of therapeutic proteins (as opposed to small molecules) in plant tissues, including mammalian antibodies, blood product substitutes (i.e. albumin), vaccines (i.e. pertussis or tetanus toxins), hormones, growth factors (i.e. vascular endothelial growth factor (VEGF), erythropoietin) cytokines and a variety of other therapeutic agents (i.e. enzymes like urokinase, glucose oxidase, or glucocerebrosidase). The use of plants for medicinal purposes dates back thousands of years but genetic engineering of plants to produce desired biopharmaceuticals is much more recent. Expression of recombinant proteins in plants has been well documented since the 1970s and has slowly gained credibility in the biotechnology industry and regulatory agencies.

Genetic engineering techniques are now available for the manipulation of almost all commercially valuable plants. Easy transformation and cultivation make plants suitable for production of virtually any recombinant protein.

Plants have a number of advantages over microbial expression systems, but one of them is of outmost importance: they can produce eukaryotic proteins in their native form, as they are capable of carrying out posttranslational modifications required for the biological activity of many such proteins. These modifications can be acetylation, phosphorylation and glycosylation, as well as others. In general, there is no restriction to the kind of proteins that can be expressed in plants.

As the demand for biopharmaceuticals is expected to increase, it would be wise to ensure that they will be available in significantly larger amounts, on a cost-effective basis.
This thesis briefly outlines the regulatory requirements necessary to registrate such a medicinal product within the European Union.

Pages: 61