Senior Researcher Shawn Fernando is responsible for bioanalytical assay development at Morphotek Inc., a biopharmaceutical company in Exton, PA, USA. Morphotek has several monoclonal antibodies in clinical development for treating cancer and inflammatory diseases. Their proprietary technology, morphogenics, increases diversity in antibody panels by suppressing mutation repair. Morphotek drives preclinical and clinical pipeline programs, and supports strategic partners with GMP manufacturing. Applying the Gyrolab® platform, Morphotek achieved a sustainable ramp-up in Phase III PK analyses to meet their drug development goals.
The Bioanalytical Development group at Morphotek faced the task of running a pharmacokinetic (PK) assay on a large backlog of samples to meet the tight deadlines of a Phase III study. Their validated assay was limited in throughput. They could see distinct advantages in transferring the assay to the Gyrolab platform, which could improve sample throughput with their available resources while sacrificing assay sensitivity.
“Our group is made up of highly trained, highly skilled individuals”, says Shawn. The hands-off approach of Gyrolab technology allows us to maximize our productivity, allowing us to meet the demands of an expanding workload. With plate-based assays, you can read a plate every 90 seconds all day long, but the assays require hands-on attention by dedicated staff, which reduces our opportunities to multitask.”
Shawn heard positive user comments at a Gyrolab Seminar and confirmed the system’s performance at an evaluation. Morphotek ordered Gyrolab xP, completed the IQ/OQ/PQ processes, and developed and validated the PK assay method. To push Gyrolab towards higher levels of throughput, they made improvements to the standard protocol.
Carry-over of samples is a concern, and may require thorough cleaning of dispensing needles. At high sample throughput, the needle wash solution they were using led to excessive salt build-up on the needles. They eliminated this by using a double-wash protocol of PBS-T and 20% ethanol.
Using reagents with a high lot-to-lot consistency is vital for regulated bioanalysis and the group solved an issue of variability in Alexa Fluor™ labeling of the detection antibody by developing their own robust protocol.
Achieving higher throughput actually shifted the bottleneck from data generation to data handling. To boost the transfer of high quality data into the database, Morphotek developed validated spreadsheets that instantly flagged failures.
“Increasing our throughput created some issues, but we solved them all,” says Shawn. “We are able to monitor assay performance thanks to our detailed data trending procedures. And we now know how to develop and run validation testing for the Gyrolab platform with a view to scaling up.”
In less than a year, the group has generated approximately 16,000 valid sample results from over 450 runs. To date, assay performance has been highly consistent, with a passing rate over 90%. Standards back-calculated from raw signal have been within 10% of the expected value for all runs to date, emphasizing the robustness of the assay.
“As part of our arsenal of instrumentation, Gyrolab helped us to be more efficient and more capable. It frees up time, maximizes group productivity and enables us to branch out into new realms”, says Shawn. “It has transformed our thinking about what we can achieve. This is in line with our striving towards innovation and inventiveness at Morphotek.”
Today, Morphotek is using Gyrolab xP for pharmacokinetic studies in Phase II/III clinical trials. “Gyrolab is considered to be a useful tool for high throughput PK analysis in our group. And we have a healthy working relationship with Gyros Protein Technologies”, concludes Shawn.
Morphotek's Bioanalytical Development group were awarded the '2012 Excellence in Ligand Binding Assays Award' by The American Association of Pharmaceutical Scientists (AAPS) for the abstract of a poster presented at the 2012 AAPS National Biotechnology Conference, held in San Diego, USA, 21-23 May.