Commentary
Biopharmaceuticals and biotechnology medicines: an issue of nomenclature

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Abstract

Over the past two decades terms such as ‘biopharmaceuticals’ and ‘biotechnology medicines’ have crept into the pharmaceutical vocabulary. Such terms often have different meanings for different people and it is perhaps time that they were more formally defined.

Introduction

The term ‘biopharmaceutical’ is one which is now in common use, but what exactly does it refer to? Pharmaceutical dictionaries contain no entry for the term, and various books published on the subject (Lubiniecki and Vargo, 1994, Zito, 1997, Walsh, 1998, Grindley and Ogden, 1999) also lack concise or clear descriptions/definitions. The general consensus, initially formed in the 1980s, seems to be that biopharmaceuticals are a class of therapeutic product produced by modern biotechnological techniques, i.e. by recombinant DNA technology, or by hybridoma technology in the case of murine monoclonal antibody based products. In essence this equated the term ‘biopharmaceutical’ with therapeutic proteins synthesized in engineered biological systems. In contrast therapeutic proteins obtained by direct extraction from a naturally producing source are not considered biopharmaceuticals. Examples of the latter include insulin extracted from pancreatic tissue of slaughterhouse animals and clotting factors extracted directly from blood.

The above description has been largely satisfactory until relatively recently. Of the 84 ‘biopharmaceutical’ products approved for medical use by mid-2000 (Walsh, 2000), 74 entirely fit this description. The remaining ten products fit less completely and of these nine antibody based products are used for in vivo diagnostic as opposed to therapeutic purposes: OncoScint and ProstaScint (Cytogen), CEA-scan and Leuko-scan (Immunomedics), Indimacis 125 (Cis bio), MyoScint (Centocor), Tecnemab K1 (Sorin), Verluma (Boehringer) and Humaspect (Organon Teknika). More significantly, nucleic acid based therapeutic agents used for antisense technology and gene therapy are now also usually referred to as ‘biopharmaceuticals’. Vitravene (ISIS Pharmaceuticals), for example, is an antisense oligonucleotide first approved for medical use in the USA in 1998. The Pharmaceutical Research and Manufacturers of America (PhRMA) report that their member companies have nine antisense and 25 gene therapy based products in clinical trials (PhRMA, 2001). In addition to the obvious fact that these are nucleic acid as opposed to protein based therapeutic products, antisense oligonucleotides are invariably manufactured not in/by a biological system, but by direct chemical synthesis.

Section snippets

Biopharmaceuticals, a definition

Given what is now considered in practice to be a biopharmaceutical, constructing a definition for this term on the basis of a single criterion (e.g. source, method of manufacture, use or structure) becomes an apparently impossible task. A combination of criteria must be employed, and the following formula of words is now proposed: “A biopharmaceutical is a protein or nucleic acid based pharmaceutical substance used for therapeutic or in vivo diagnostic purposes, which is produced by means other

Biotechnology medicines

‘Biotechnology products’, ‘biotechnology medicines’ and ‘products of pharmaceutical biotechnology’ are terms also now sometimes used (interchangeably) within the pharmaceutical sector. They are frequently used by, for example, PhRMA in relevant reports (PhRMA, 2001). Again, in the absence of a precise definition, the range of substances encompassed by these terms, and their relationship to the term ‘biopharmaceutical’, remains to be fully explored.

As used by PhRMA these terms encompass “only

Current regulatory terminology

The relationship between the terms and definitions proposed and formal regulatory terminology is of obvious importance. In this context ‘biologic(s)’ as well as ‘biological response modifier(s)’ are the relevant FDA terms while, in the European Union, the EMEA employs the term ‘biological medicinal product(s)’.

The FDA definition of a biologic (biological product) is: “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product or analogous

Conclusion

It becomes obvious from the above discussion that straightforward classification of many modern biotechnological based pharmaceutical products using traditional industry and/or regulatory terminology is a difficult task. The lack of precise definitions for broadly accepted categorizations of such pharmaceutical products merely reflects the speed at which the biotechnological-related pharmaceutical sector has grown over the last two decades. However, given that almost 100 such products have now

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