Delivering in vitro DM assay services

Transcription

1 Delivering in vitro DM assay services UGM_BIORAILS Copenhagen, Oct 2017 Annalisa Pellacani

2 An Integrated Approach to Drug Discovery: from Target to Clinic Target ID and Validation Screening and Hit ID Hit to Lead Lead to Candidate Candidate to Clinic Aptuit Integrated Services Aptuit s integrated approach, with all aspects of the project being managed by experienced scientists, will increase the speed of the drug discovery process from target to clinic and maximise the chances of success. 2

3 From Hit to Candidate: Drug Metabolism and Pharmacokinetics (DMPK) Aptuit offer a comprehensive and flexible range of ADME and PK experimental services. We offer a combination of routine and bespoke assays, delivering high quality coupled with cost effectiveness to suit the needs of our individual clients. DMPK at Aptuit consists of experienced DMPK scientists running a large variety of assays, as well as providing key scientific input for integrated projects. Solubility LogP LogD PAMPA Caco-2 MDCK-MDR1 Plasma Protein Binding Tissue Protein Binding Blood partitioning Absorption Distribution Metabolism Excretion Microsomal Stability Hepatocyte Stability Plasma and Simulated Fluids Stability CYP450 Inhibition Metabolite Identification Pre-clinical species PK (PO, IV, IP, SC, IM) Bile Duct cannulation 3

4 DMPK Workflow Request Requests Processing Assays Data Analysis Data Reporting ELN Project Reps insert requests Assay Scientists collect requests and set-up experiments Assay performed and data collected Data analysed and results produced Data reported to customers Data stored Critical: based on Excel files, one user at a time, no control over progression status, no controls on Compound ID consistency Critical: based on Excel files, manual copy-paste, timeconsuming, non-standard reports, not searchable results, paper LNB 4

5 BioRails/Morphit: a solution In 2016 we decided to implement BioRails, together with Morphit to address these topics Improve requesting phase easy access to multiple users track of request progression check of Compound ID against Inventory match Compound ID to Project ID Improve Data Analysis minimize manual copy-paste direct upload of raw data files improve data analysis template performance (less time spent) Improve data management reports automatically generated results stored in DB (searchable) data storage in elnb 5

6 Request and Requests Processing Requests can be entered by multiple requestors at a time and based on assay type, more assays can be selected at the same time Linking the BioRails DB to Aptuit Inventory system allows validation of compound IDs selected for testing and their association with Project ID Specific assay conditions such as matrix, species, cell types are selected by the requestor among a list of available As long as new conditions are needed (i.e.new matrices or species) they can be added to the list Requests are picked by assay responsible scientists and processed 6

7 Assays selection 7

8 Request and Requests Processing Requests can be entered by assay type, more assays can be selected at the same time Linking the BioRails DB to Aptuit Inventory system allows validation of compound IDs selected for testing and their association with Project ID Specific assay conditions such as matrix, species, cell types are selected by the requestor among a list of available As long as new conditions are needed (i.e.new matrices or species) they can be added to the list Requests are picked by assay responsible scientists and processed 8

9 Compounds selection Import directly a.txt file Paste from a list Select from Inventory DB Input validated against Inventory before proceeding 9

10 Request and Requests Processing Requests can be entered by assay type, more assays can be selected at the same time Linking the BioRails DB to Aptuit Inventory system allows validation of compound IDs selected for testing and their association with Project ID Specific assay conditions such as matrix, species, cell types are selected by the requestor among a list of available to simplify and speed up request insertion As long as new conditions are needed (i.e.new matrices or species) they can be added to the list Requests are picked by assay responsible scientists and processed 10

11 Assay Conditions selection 11

12 Request and Requests Processing Requests can be entered by assay type, more assays can be selected at the same time Linking the BioRails DB to Aptuit Inventory system allows validation of compound IDs selected for testing and their association with Project ID Specific assay conditions such as matrix, species, cell types are selected by the requestor among a list of available As long as new conditions are needed (i.e.new matrices or species) they can be added to the list to ensure flexibility Requests are picked by assay responsible scientists and processed (status tracking) 12

13 Managing Requests by Queues Request status It changes according to workflow progression Result Task Populated when the assay starts 13

14 Request Tracking The whole workflow is tracked ensuring an accurate activity planning and data delivery. Workload assignment and activity planning can be managed by the Request queue Each progression step is identified by a proper status Turn-around time can be easily measured Metrics can be extracted such as compounds/assay or request/project Status of activities can be monitored by querying the DB 14

15 DMPK Workflow Request Requests Processing Assays Data Analysis Data Reporting ELN Project Reps insert requests Assay Scientists collect requests and set-up experiments Assay performed and data collected Data analysed and results produced Data reported to customers Data stored Critical: based on Excel files, one user at a time, no control over progression status, no controls on Compound ID consistency Critical: based on Excel files, manual copy-paste, timeconsuming, non-standard reports, not searchable results, paper LNB 15

16 Data Analysis and Reporting The availability of specific Morphit protocols for each assay allows to directly upload raw data generated by the instruments and to analyze and produce results by a pre-defined calculation template. Minimizing manual data manipulation guarantees a more robust and safer approach to data integrity. Results can be reviewed and uploaded to the BioRails database in one click 16

17 Data Integrity Direct access to the proper Morphit analysis template through the link 17

18 Morphit Analysis Template Instructions panel Pre-defined calculation rules Interaction with data Direct Upload to Biorails 18

19 Data Integrity Results and their related information and documents must be collected and kept in a safe environment In BioRails raw data, results and any other required piece of information (i.e.assay protocol, CoA) are stored and signed as in commonly used electronic lab notebook to guarantee long-term data availability and proper data segregation. Moreover, witnessing procedure is available. 19

20 Data Integrity Add To upload files such as CoA, method sheets, chromatograms Task Status Identify the status of the process. When Published Sign option becomes available Signing the experiment locks it by unique checksum 20

21 Witnessing 21

22 Conclusions Working in a CRO environment requires clear and safe tracking processes to ensure Meeting the delivery timelines Data segregation Data integrity Proper workload distribution BioRails/Morphit can provide a support to all these requirements and contributes to improve overall productivity Estimated time saved: Request management ~ 8 h per week Data Analysis ~ 1 FTE Data Storage (elnb) ~ 0.5 FTE Further steps Improve reporting Add new groups of assay (i.e.in-vivo DMPK studies, in-vitro Pharmacology studies) 22

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