Biomedical Engineering Reference
In-Depth Information
In addition,a more efficient primary drug screening and hit validation is neces-
sary to minimize the costs.In total,for the discovery,development and the intro-
duction of a new drug to the market including the costs for discontinued devel-
opment projects about $300 to $500 million have to be estimated [350].On the
other hand,the number of new chemical entities (NCE,ca.50 per year) is near-
ly constant since 1983 while the costs increased more than three times [351].
On this background laboratory automation in the early stages of drug devel-
opment is able to enhance productivity,efficiency,reliability,and speed without
increasing research costs. Typical assay costs in HTS are 1$/sample. Testing
200,000 compounds in 20 screens would then cost $4million.It is expected that
the costs can be brought down to less than $0.1/sample in defined cases by
making use of effective screening technologies and miniaturization. However,
sample sourcing from automated parallel synthesis or extracts from natural
sources is even more expensive [352]. HTS therefore is not an inexpensive
enterprise.
5.4.2
Sample Sourcing
Natural products and its analogs are important sources for novel lead struc-
tures. Due to the complexity of cellular metabolism, extracts from natural
sources usually contain numerous different components in varying amounts.
Therefore,integration into automated drug screening approaches adds additio-
nal efforts. Dealing with rough or enriched extracts from natural sources is
highly cost-intensive but of remarkable interest. Up to the present, extraction
procedures in order to prepare samples for drug screening are usually per-
formed with a low automation rate. There exist a strong need in automation
approaches for routinely performed procedures.
Recently, Merck KGaA in Darmstadt in cooperation with AnalytiCon AG
(Berlin) presented a HPLC-based Workstation (SepBox) designed for the extrac-
tion and separation of plant material in a more preparative scale which has also
successfully been used for the separation of secondary metabolites from culture
broths ofmicroorganisms.On the other hand,it has been shown that automated
solid phase extraction (SPE) can achieve high quality samples from cultivation
ofmicroorganisms in an easy and cost-effective manner.In the latter case modi-
fied Zymark RapidTrace modules have been used in the automation concept
which advantageously does not need HPLC-techniques [353].
Analysis of the sample quality either from synthesis approaches or from
natural sources is usually performed by techniques like HPLC and capillary
electrophoresis (CE) coupled to UV/VIS-,MS-,IR-,or NMR detection.Because
the working procedures of these instruments are more or less serial,there exist
an enormous need in new technologies allowing parallel performances and
further miniaturization.
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