19.03.2015 |

LOGFILE No. 17/2015 – Types of Biotechnological Active Substances

Types of Biotechnological Active Substances

An excerpt of the GMP MANUAL

by Dr. Rainer Gnibl

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.

What are biotechnological active substances?

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,, 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.

Which types of biotechnological active substances can be distinguished?

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:

  • Manufacturing method or process (e.g. cell culture, fermentation, genetic engineering, hybridoma technology, extraction from biological tissues, reproduction of agents in cell cultures, embryos or animals)
  • Origin of starting materials (e.g. human, animal, microbial, herbal origin)
  • Molecular structure (e.g. chemically synthesized compound, amino acid, sugar, protein, nucleic acid, cell, tissue)
  • Physiologically or pharmacologically active mechanism (e.g. antibiotic, immunological, allergenic, genome modifying)

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
Blood products

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 of the GMP MANUAL, Chapter 21.G Biotechnological Active Substances.


Dr. Rainer Gnibl
GMP Inspector
Regierung von Oberfranken
E-mail: rainer.gnibl@reg-ofr.bayern.de