The Drug development process - Pharmaceutical Biotechnology: Concepts and Aapplications - page 68

acid sequence/expression levels of a protein and, hence, affect its functional attributes. SNPs
largely account for natural physical variations evident in the human population (e.g. height,
colour of eyes, etc.).
The presence of an SNP within the regulatory or structural regions of a gene coding for a pro-
tein that interacts with a drug could obviously infl uence the effect of the drug on the body. In this
context, the protein product could, for example, be the drug target or perhaps an enzyme involved
in metabolizing the drug.
The identifi cation and characterization of SNPs within the human genomes is, therefore, of both
academic and applied interest. Several research groups continue to map human SNPs, and over 1.5
million have thus far been identifi ed.
By identifying and comparing SNP patterns from a group of patients responsive to a par-
ticular drug with patterns displayed by a group of unresponsive patients, it may be possible
to identify specific SNP characteristics linked to drug efficacy. In the same way, SNP pat-
terns/characteristics associated with adverse reactions (or even a predisposition to a disease)
may be uncovered. This could usher a new era of drug therapy where drug treatment could
be tailored to the individual patient. Furthermore, different drugs could be developed with
the foreknowledge that each would be efficacious when administered to specific (SNP-de-
termined) patient sub-types. A (distant) futuristic scenario could be visualized where all
individuals could carry chips encoded with SNP details relating to their specific genome,
allowing medical staff to choose the most appropriate drugs to prescribe in any given cir-
cumstance.
Linking specifi c genetic determinants to many diseases, however, is unlikely to be as straight-
forward as implied thus far. The progress of most diseases, and the relative effectiveness of allied
drug treatment, is dependent upon many factors, including the interplay of multiple gene prod-
ucts. 'Environmental' factors such as patient age, sex and general health also play a prominent
role.
The term 'pharmacogenomics' is one that has entered the 'genomic' vocabulary. Although
sometimes used almost interchangeably with pharmacogenetics, it more specifi cally refers to
studying the pattern of expression of gene products involved in a drug response.
4.8 Initialproductcharacterization
The physicochemical and other properties of any newly identifi ed drug must be extensively char-
acterized prior to its entry into clinical trials. As the vast bulk of biopharmaceuticals are proteins,
a summary overview of the approach taken to initial characterization of these biomolecules is
presented. A prerequisite to such characterization is initial purifi cation of the protein. Purifi cation
to homogeneity usually requires a combination of three or more high-resolution chromatographic
steps (Chapter 6). The purifi cation protocol is designed carefully, as it usually forms the basis of
subsequent pilot- and process-scale purifi cation systems. The purifi ed product is then subjected to
a battery of tests that aim to characterize it fully. Moreover, once these characteristics have been
defi ned, they form the basis of many of the QC identity tests routinely performed on the product
during its subsequent commercial manufacture. As these identity tests are discussed in detail in
Chapter 7, only an abbreviated overview is presented here, in the form of Figure 4.5.