When it comes to biotechnological active substances, the variety of different products and associated manufacturing processes is clearly greater than in the classic manufacture of active substances. Particularly the origin and makeup of the starting and raw materials used here are often specifically related to the product. It follows that the controls and tests to be applied to these materials differ accordingly, as do the resultant control strategies of the relevant manufacturing process.
To begin with, we should distinguish between biological active substances and biotechnological active substances.
According to Directive 2001/83/EC „Community code relating to medicinal products for human use“, Annex I, Part I, 18.104.22.168, biological active substances are manufactured from starting materials of biological origin. These starting materials can be micro-organisms, organs, tissues of herbal and animal origin, cells or fluids of human or animal origin (including blood or plasma) and biotechnological cell structures (cell substrates, recombinant or non-recombinant, including primary cells). Thus, the term biological active substance is a comprehensive term that also covers biotechnological active substances.
A distinctive feature of the production of biotechnological active substances is that they are manufactured using cells or organisms that were generated or modified with recombinant DNA, hybridoma or other technologies. This means that biotechnological active substances are defined by the technologies applied to manufacture them. They are obtained from or produced with the aid of living starting materials (cells or organisms). These starting materials no longer bear much resemblance to the natural source; on the contrary, their genetic make-up has been modified by means of the above-mentioned technologies. They are produced with the aid of cell cultures or by fermentation and they usually consist of macromolecular substances such as proteins and polypeptides. However, biotechnological processes can also be used to produce micromolecular active substances such as antibiotics, amino acids, vitamins or carbohydrates.
The large number of different products involved makes it difficult to render a clear categorisation of biotechnological active substances. Criteria for distinguishing between these categories could include:
It is not always possible to make an unequivocal categorisation, nor is it always feasible to do so. What we intend to do here is rather to give an impression of the high degree of variance and diversity within this class of products. Other groups of products and corresponding examples are compiled in Figure 1. It should be noted here that it is quite possible to produce some of the biotechnological products given in the figure using conventional methods without biotechnological process engineering, or to modify them with chemical partial synthesis even after the biotechnological process has been completed.
|Types of biotechnological products||Example|
|Micromolecular recombinant products||Antibiotics, hormones, amino acids, viatamins, carbohydrates|
|Macromolecular recombinant products||Monoclonal antibodies, interferon, insulin, allergens|
|Hybridoma products||Monoclonal antibodies|
Clotting factors, immunosera, polyclonal antibodies
|Nucleic acid products||Vaccines, gene therapy medicinal products|
|Cell products||Somatic cell therapy medicinal products|
|Tissue products||Tissue engineered products|
Figure 1: Types of biotechnological products
The text is an excerpt from GMP Series Managing GMP Requirements in Biotech API Manufacturing.
Don’t miss ordering your copy of Managing GMP Requirements in Biotech API Manufacturing
Dr. Rainer Gnibl
GMP-Inspektor, Regierung von Oberbayern