Manufacture of Betaferon®
Betaferon® is made using recombinant DNA technology, a highly sophisticated process that is difficult to develop to commercial levels. There are seven basic stages in the manufacturing process.
1) Obtaining an interferon beta gene
The first stage in the manufacture of Betaferon® is to extract the gene coding for interferon beta from human fibroblast cells.
2) Modifying the gene
The gene is then modified biochemically to produce interferon beta-1b, which is a more stable molecule.
3) Making a recombinant DNA molecule
The modified gene, now coding for interferon beta-1b, is inserted into a plasmid (a circular DNA vector) to produce a recombinant DNA molecule.
4) Adding the recombinant DNA molecule to a bacterium
Recombinant DNA molecules, consisting of the modified gene in a plasmid, are added to an E. coli bacterial culture. The bacteria retain their own DNA, and the recombinant molecules exist alongside as additional pieces of genetic material.
5) Producing interferon beta-1b by bacterial fermentation
Large numbers of interferon beta-1b-producing E. coli can be produced by bacterial fermentation. As the bacteria multiply, the recombinant DNA and the DNA of the bacterial host are replicated in tandem. The bacterial transcription and translation mechanisms read the genetic information contained in the plasmid as well as their own, and produce interferon beta-1b. Interferon beta-1b is then secreted into the culture medium.
6) Extracting interferon beta-1b from the ferment
The interferon beta-1b is harvested from the ferment, and then purified.
7) Adding inactive ingredients
Inactive ingredients, which act as stabilisers, are added to the purified interferon beta-1b. The stabilisers used are mannitol and human albumin. Betaferon® is supplied as a highly purified, sterile, lyophilised (freeze dried) powder.
