A Compound Management Group Ensures Quality

May 25, 2016

drug-discovery In drug discovery, delays are inevitable but costly. Each day lost increases the timeline to potential revenue, which can be as much as millions of dollars per day for top-selling drugs like Cymbalta1.

What can companies do to keep projects moving as smoothly as possible? According to one scientist who heads a big pharma compound management group*, being proactive is a huge part of the efficient drug discovery equation. “What we’re hoping to do is prevent issues from ever occurring in the first place.”

For the times when automation doesn’t work

Supporting a variety of screening efforts, this compound management group maintains stocks of solubilized and dry compounds, preparing tubes and plates as requests come in. For the most part, the system is highly automated with eight liquid handling robots and an automated compound store, all tied together with a LIMS system. Because everything is automated, requests are usually filled quickly and efficiently.

“Automation is great when it works,” says the team lead, but every once in a while a problem occurs. According to this scientist, problems are typically sporadic, unpredictable, and seem to come in waves, which can make them hard to avoid. One problem that they’ve now solved is the presence of the occasional empty well, something that can frustrate screeners as they try to cover the chemical space targeted by the medicinal chemists.

384-well plates have densely-packed wells making it hard to tell by eye if every well is filled or not. This can lead to empty wells going unnoticed until after the data is in and inconsistencies appear. Or the empty well might not ever be noticed at all, resulting in possible missed hits and lost opportunities.

In the lead scientist’s experience, empty well issues can be hard to address—was it user error in plate handling? Was it a liquid handler error during plate preparation? Did something happen during transport? Was the stock solution unexpectedly low? To help address the empty well problem, the lead scientist recently brought Artel’s VMS Volume Measurement System into his lab. With the VMS, he and his team can quickly check each and every plate for empty wells. Using a pressure-based technology, the VMS provides measurement of a well’s volume—whether the contents are solid, liquid, or a slurry—in only 35 seconds for 96-well plates or 110 seconds for 384-well plates.

“With the VMS, we can eliminate one of the variables,” says the lead scientist, “and head off any issues for the screeners before problems arise.” This saves everyone time by reducing efforts and resources wasted on empty wells. In addition, troubleshooting is streamlined as efforts can be focused on where the issue occurred—either during plate preparation or after. And in drug discovery, time saved can mean a great deal of money.

Ensuring that automation is working well

But ensuring full wells is just one way the compound management group does their part to speed drug discovery. Another proactive measure they take is to ensure that all eight liquid handlers are performing within specifications by testing their performance every two- to three-weeks. For this job they turn to Artel’s MVS Multichannel Verification System. With the MVS, they can quickly check the accuracy and precision of the lab’s automated liquid handlers using a two-dye ratiometric approach rather than by the more time-consuming and less accurate gravimetric method.

You don’t want people running experiments with bad instruments.”

—Compound Management Scientist*

By testing the lab’s liquid handlers every two- to three-weeks, the group balances risk versus time spent testing performance. In the extremely unlikely worst case scenario that an automated liquid handler goes out of spec immediately after being tested, only two-week’s worth of data would be compromised. They further optimize performance verification workflows and spread out risk by only checking one or two instruments at a time as scheduling permits. This way there’s always at least one recently verified instrument in operation. “You don’t want people running experiments with bad instruments.”

Keeping afloat when budgets are tight

Times are tough in drug discovery and development, with teams expected to deliver better hits with fewer resources. In the face of budget limitations, the lead scientist’s proactive measures have been a big success with management—the VMS and MVS have been among the few new instruments the Compound Logistics Group has gotten approval for in the past few years.

“We’re trying to do the best we can with what we have,” says the team lead. “Being able to verify what we have has become more important than getting something new. If we can utilize older equipment longer because we’re able to trust it, then that’s a good deal.”

Being proactive just makes sense

Finding tomorrow’s next therapeutic can be a difficult, costly, and time consuming venture. For the lead scientist and his compound management group, preventing problems before they arise and catching issues quickly is one way to keep drug discovery as efficient as possible.


Additional Resources


References

1. Statista website. Top antidepressant drugs in the United States based on revenue in 2011-2012 (in million U.S. dollars). http://www.statista.com/statistics/242644/revenues-of-top-depression-drugs-in-the-us-2011-2012/. Accessed December 3, 2015.


*This case study highlights the experiences of a compound management scientist whose company asked to remain anonymous.