Incorporating Sample Collections From Acquired Companies into GSK – Simple?

1. Incorporating Sample Collections From Acquired Companies into GSK – Simple? Darren Rimmer Principal Scientist GSK Stevenage 4th September 2013 Property of GlaxoSmithKline

2. Abstract • Within large Pharma, the acquisition of smaller companies is becoming more common. One of the consequences (and challenges) of company acquisition, is how Compound Management groups incorporate the acquired sample collections into current corporate sample collections. This talk shares a description of how GSK performed this with the recent acquisition of Cellzome and the importance of quality checks both from an IT and an Analytical perspective. Property of GlaxoSmithKline

3. Challenges of Incorporating Compound Collections • Formatting of inventory data – GSK vs NewCo formats? • Compound registration practices? • Automated storage vs manual storage? • Differing labware types?

4. Background • GSK examples of smaller company acquisitions • Sirtris (2008) • Human Genome Sciences (2012) • Cellzome • Drug discovery company identifying new generation of kinase-targeted drugs to treat inflammatory diseases • Based across 2 sites • Chesterford Park (CP), Cambridge UK • Solid collection ~6000 • Solution collection ~7000 • Heidelberg (HDB), Germany • Solution collection ~70,000

5. Compound Management GSK Harlow 3 M solutions (cap.4M) 1.6 M solids (cap.2M) Philadelphia 2.5M solutions (cap.2.8M) North Carolina 0.7 M solutions (cap.2M) Madrid 2.5 M solutions (cap.2.6M)

6. Sample Processing - Solutions

7. Data Checks • Comparison of Cellzome and GSK Registration databases • Registrars checking structure representation – SMILES string • Registration then undertaken on ~80,000 structures – without this step, no downstream processes can occur! • Computational chemists also performed comparisons of Cellzome’s collections vs the GSK collections - helped to determine the value of compound addition to GSK’s collections

8. Compound Processing - Solutions • CP Solutions had no accurate volume recorded • Use of Brooks Tube AuditorTM(TA*) to obtain accurate volume of individual Tubes *(GSK own a prototype version) • Allowed measurement of solution +/- 10ul within each matrix tube • Processes a rack of 96 Tubes at a time • A row of 8 tubes at a time are picked up and an image is created:

9. Compound Processing - Solutions • The TA then detects the bottom of the tube and the meniscus of the solution within each tube to create a measurement, which is then used to calculate the individual volumes • Once the tube volumes have been measured, an output file is created

10. Compound Processing - Solutions • Before running each tube rack from CP, we had to remove the labels on each tube. Leaving these labels on meant inaccurate readings from the TA as it confused the meniscus with the top/bottom of the label itself • Non-barcoded Matrix tube • Matrix type 1 • Matrix type 2 • ABGene tube • The positions of the tubes within each rack were also checked against the Inventory details, for confirmation that tubes were physically in the correct positions

11. Data Capture and IT Requirements • At this stage we now have a file created from the Tube Auditor, plus the original manual inventory from CP Cellzome • IT ‘application’ required plus design of workflow for the transfer of Cellzome Matrix tubes into GSK ABGene tubes: TA creates CSV file Load file into Cellzome application Run Evo ABGene tube scanner creates CSV file Load compounds into GSK solution store Quality control LCMS

12. Compound Processing - Solutions • TecanEvoTM used for the solution Tube to Tube transfer • The ‘Cellzome application’ creates a file to run on the EvoTM using EVOwareTM • EVOwareTM file contains details of Matrix rack name, volumes in each tube and their position within the Matrix tube rack • The output of the EVOwareTM is a file that contains the new ABGene tube rack barcode, volumes in each tube and their position within the ABGene tube rack

13. Quality Control of Cellzome Solutions • The GSK QA project established a baseline for the quality of compounds in the GSK screening collection • GSK now has an industry-leading high quality collection due to ongoing QA • Cellzome collection required QA prior to inclusion in the compound collection • Chesterfield Park Solutions - LC-UV-MS of all solutions (~7k) • Heidelberg Solutions - 10% selected for LC-UV-MS as ~70k in total • Purity and identity fails were removed following analysis • 10% of all the compounds submitted for QC ~1.4K were analysed using Chemiluminescence Nitrogen Detection (CLND) to get an idea of the concentration

14. QC Results LC-MS Analysis • 6580 Chesterfield Park solutions were analysed by LCMS with 94% pass rate. • 6000 Heidelberg solutions were analysed by LC-MS with 97% pass rate. • Heidelberg solutions were externally acquired from many different suppliers. • Cellzome had carried out their own internal QC on these samples. • Majority of suppliers had a >90% pass rate and identification of poor quality suppliers were consistent with GSK’s experience.

15. QC Results CLND Analysis • CLND was completed for approx 10% of compounds. • Expected concentrations were 30mM for Chesterfield Park and 10mM for Heidelberg. • There was a spread of concentration values obtained, with the Heidelberg solutions being closer to their target value of 10mM.

16. Conclusions • Main conclusion – resource intensive and longer than expected to complete • Data integrity • Demonstrated the need for careful data management in the use of automated stores • HDB data • Volume tracked by Inventory management application • Use of the Brooks TA was crucial for determining volumes of the CP solutions • CP solutions removal of labels for identification (7000 in total!) • Detection of precipitates • Good data increases confidence of having the right sample, with the right data each time

17. Conclusions – QC LCMS • Use of high throughput LCMS allowed a high number of compounds to be analysed in a short period of time • Provided confirmation of high quality collections from CP and HDB. Was also crucial in highlighting any compound processing errors during the tube to tube transfers • The 10% HDB solution samples QC’d was a large enough set to give confidence for the total set of samples received for transfer. • The LCMS checks have proved vital for determining the required purity and correct identity of samples entering the GSK solution collections • Maintains the high integrity of any solution collection and provides confidence in the quality of compound handling processes

18. Acknowledgements • Emily Munsey, Industrial placement student (University of Bath), SMTech GSK • David Leigh, SMTech GSK • Warren Miller, Cellzome IT • Friedrich Reinhard and Christina Rau, Cellzome • Nigel Ramsden, Cellzome • Julie Quayle & Zoe Blaxill, Analytical Chemistry GSK • Ken Miles, SMTech IT GSK • Rob Hughes & Neil Hardy, SMTech Automation GSK • Ian Mawer, Registrar GSK • ....and many others from Cellzome and GSK • Tecan • RTS

19. Property of GlaxoSmithKline