Portfolio managment:Layout 1 14/1/10 20:10 Page 14
Business
of a few weeks
6
. Established HTS functions are
able to mount and complete 40-60 campaigns per
annum on a steady-state basis
7
.
To realise this capability, several discrete activi-
ties need to converge. These include, at-scale pro-
tein expression, the provision of live cells on a just-
in-time basis, assay development, adaptation to
automated operation, the provision of compounds
from the corporate collection and the securing of
large stocks of assay-specific reagents and consum-
ables
8
. HTS has developed as a discrete discipline
over the past 15 years. During its early years HTS
underwent many of the issues described in Stage 2.
Organisational expectations for delivery were
unclear, and often over-sold. It constantly had to
justify its existence and value to organisations
which had traditionally undertaken lead identifica-
tion within Therapeutic Area teams working on an
Figure 2 (above): Portfolio balancing risk and reward. Hypothetical portfolio of 50 projects iterative basis with medicinal chemistry teams.
in which projects of lower feasibility but higher value are balanced by projects with high
While this uneasy impasse existed for several years
feasibility
in many organisations, HTS ultimately became the
Figure 3 (below): Portfolio focused on safer projects with a higher return. Hypothetical
accepted means of prosecuting early stage lead
portfolio of 50 projects in which resources are focused on projects of high value and
identification within almost all pharmaceutical
feasibility organisations. This was accomplished by a combi-
nation of realistic expectation setting, transparency
of progress and ultimately because evolving HTS
capabilities in terms of assay throughputs eclipsed
what could be supported within Therapeutic Area
teams. To maintain close alignment of HTS and its
supporting activities within Pharmaceutical
Discovery, it was necessary to develop a number of
communication and management capabilities.
These are discussed further below.
For a core HTS function supporting multiple
therapeutic areas, maintaining communication
across the Discovery organisation is key. At a basic
level, the HTS group ensures that its screening data
sets are made available, in a standard format, to
the wider organisation via a standard results data-
base. Outside the needs of their immediate client,
this allows chemi-informatics analyses within tar-
get classes and across research areas, a level of con-
sistency not possible if screening were solely with-
in the remit of individual Disease Area teams.
At the next level, campaign progress is made
Stage 3: Maintaining alignment and available to the wider organisation via intranet
measuring impact sites allowing an at-a-glance assessment of status
The third example of the application of the PPM of any one campaign. Related to this is the extrac-
techniques developed at Wyeth focuses on main- tion and publication of metrics about how long it
taining alignment of HTS with the needs of the actually takes to generate a stable method fit for
Discovery organisation. HTS is a core Discovery at-scale operation, validation thereof and securing
Pharmaceutical capability that enables early stage of all key reagents necessary for prosecution of
Discovery programmes to screen the entire corpo- campaign, as well as the time to complete the
rate compound collection, typically comprising screen itself. In an environment where the mantra
0.4-1.0 million discrete compounds, in a timescale has become “we screen our compound collection
14 Drug Discovery World Winter 2009/10
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