Screening


the greatest achievement of HTS in respondent’s organisations. This was followed by enabled targets to be screened faster, better quality data points to be generated, and then enabled many more targets to be screened. Rated as least achieved was responsible for compounds in clinic, increased the bottom line (ie, company profits), and brought new drugs to the market earlier. Clearly respondents view their efforts in running HTS systems somewhat detached from those of their company goals as a whole. This view was reinforced by the answers we got to the ques- tion, does system reliability affect your organisa- tion’s drug discovery success? (Figure 9). The major- ity (35%) of respondents thought system reliability had a minor effect on their organisation’s drug dis- covery success, with a further 8% claiming it had no effect. However, of the remaining respondents 57% thought its effects were greater (rated moderate, important or major). Only 17% believed system reliability had a major effect, and 25% an important effect on their organisation’s drug discovery success. If having a fully operational system is key to suc- cessfully running screens, it is difficult to compre- hend how this is also not of major importance to an organisation’s drug discovery success.


Putting a cost on unscheduled downtime


When respondents were asked to quantify the cost of unscheduled downtime or system failure the mean cost of lost operation was estimated to be $5,800/day (24h) (Figure 10). However, there was quite a spread of estimates with 19% suggesting a value of <$500/day. Put perhaps most interesting- ly, 44% of respondents did not know or were not able to assign a cost to their lost downtime, sug- gestive of the fact they had not fully considered the impact (the cost) associated with lost downtime. However, respondents were able to put forward values for the uptime that might be gained if their systems were more reliable, and this was a median of two additional days operational per month and one additional primary screens per year. The most accessible cost associated with poor system relia- bility can probably be gauged from the estimated cost of repeating the unacceptable wells (those excluded) per screen, and in this case respondents reported a mean cost (ie, additional reagent and plate cost only) of $15.3K/biochemical screen and $16.4K/cell-based screen.


What are system integrators doing to improve system reliability?


Rather than review a list of features and benefits of the various system integrations on offer, we asked


Drug Discovery World Winter 2010/11


Figure 7: Realistic advantages of improved HTS system reliability


Increase user (customer) satisfaction Run screens quicker


not meet acceptance criteria) Repeat fewer wells (where data does


Use for application beyond original scope (eg profiling) Achieve better Z’ values Use less reagent per screen Reduce the cost of screening Make greater use of the system Meet more screening deadlines


Identify weaker inhibitors Reduce number of false positives Discover more lead series Increase hit confirmation rate


© HTStec 2010


3.37 3.39 3.43


3.29 2.61 2.38


2.22 2.25 2.26


1.86


1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 Rating SCORE 1 to 5, where 1 = very unlikely and 5 = highly likely


4.14 3.73 3.57


Figure 8: What HTS has achieved to date in respondent’s organisations


Enabled many more targets to screened Better quality data points generated Enabled targets to screened faster More data points screened


More on time delivery of screening results Streamlined/enhanced the lead


discovery process


Made possible cost savings and efficiencies Facilitated improvements in quality


Enabled targets to be screened with greater accuracy


Identified numerous lead series Driven and shaped compound management


Driven new technology adoption and innovation


Increased hit confirmation rate


up and downstream Driven technology transfer


Responsible for compounds in clinic


Increased the bottom line (ie company profits)


Brought new drugs to the market earlier © HTStec 2010 2.52


1 1.5 2 2.5 3 3.5 4 4.5 5 Rating SCORE 1 to 5, where 1 = not acheived and 5 = definitely acheived


2.94 2.98


3.62 3.47 4.72 4.4 4.36


4.12 4.16


4.02 4.06


4 3.98


3.9 3.92


3.82


Figure 9. How HTS system reliability affects respondent’s drug discovery success


Important effect Moderate effect Minor effect No effect


Major effect 0% © HTStec 2010 8% 35% 15% 25% 17%


5% 10% 15% 20% 25% 30% 35% 40% % Responding


65


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