2006 Cpsa - Poster - Analytical Chemistry Informatics Suite

BioAnalytical Manager v1.0

Abstract The ability for Analytical Chemists to impact the drug discovery process will be dictated by their applied informatics tools; which will provide efficiency to their workflow and effectiveness in their data communication. Focused Analytical Informatics solutions have been developed by Kalypsys for varying responsibilities. Open Access Support Intranet information solution was constructed to act as a repository for all information concerning each system: • system status • troubleshooting log • standard LC/MS traces which are automatically posted daily • backpressure log • contact information for all applicable vendors BioAnalytical Workflow Management • BioAnalytical Analysis, a server-based experiment tracking system, was developed to assist communication between the analysts and clients. • Mandatory inclusion of demographics and data files has produced a system where workload can be anticipated, and forensic tasks simplified.

BioAnalytical Manager v2.0

Background: Prior to Informatics solutions: • BioAnalytical workflow management was performed in meetings, by email and through the use of a project whiteboard. • This process was conducive to misinformation, mishandling of study analysis and inability to track progress.

Background: BioAnalytical Manager v1.0 revolutionized the workflow for the department. Rate limiting steps for BioAnalytical work were identified: • Human sample PLATEMAP preparation • Report authoring • Result table generation BIOANALYTICAL MANAGER v2.0 • Freezer sample BIOANALYTICAL management PLATEMAP

Purpose: This manager is the definitive record of Kalypsys BioAnalytical work, both internal and external. • It is a resource for tracking analyst assignments • Monitor study progression through the various stages • Document posting for each study (sample receipt, reports, etc.) • Built-in email communication allows for updates and notifications

ENGINE

Direction: Design more active content: • Passive resource that only accepts information • Generation of files to better automate the analysis of samples • Server based data processing tools designed to auto-generate reports

Document Management • The homogenizing solution for the data handling has been the emergence of auto-generating PDF reports. • Created by server applications that can be e-signed before distribution. • Power of producing historical reports with pertinent experimental sections,

Direction: The implementation of the solutions contained in this release will greatly impact the capacity of work that an analyst will be able to perform. • The introduction of data into the system through this version provides for a wealth of information to be made available. • Implementation of this data into SAR table generation

Verapamil

Figure 2: Studies arranged in tabs by stage

Background: Utilizing the SharePoint® internet tools provided on the Kalypsys® intranet, a system management webpage was created to track and publish system events. The page evolved to include: Analytical Support Group Point Person

Automatically posted Standard

Daily Backpressure Log

Important Documents

Troubleshooting Log

System Component Information

Surveys

Figure 3: Details page for a study

Purity

Background: Solubility is performed using the Millipore Multiscreen® Solubility Plate. • Stated throughput for this assay is 28 compounds per week • Previous data handling: Excel Macros • Solubility Manager deployed; online curate and assay management • Solubility Test Sets are processed by the server into PDF reports. Purpose: Solubility is deployed as a post biological screening assay. • The assay is typically used to diagnose problem compounds • Requested for data gathering with little consideration for the results. • Needs to be positioned as a mandatory assay

Purpose: As Kalypsys® has engaged itself in the application of uHTS technology, the throughput that is necessary to support the hits resulting from these screens must be optimized: • Shorter sample cycle time • Automated data processing • Purity during library building for efficiency in the subsequent testing • Database storage; easy access and data mining capable • Internet access to plate and sample traces

Direction: To position the assay accordingly in the discovery process it must be made cost effective, high throughput and capable of delivering data that is pertinent to the projects. • Kalypsys® has initiated technology development projects • With Solubility Manager, the individual data is drawn into information engines (i.e. SAR table generator) • Queuing system allows for workflow management

Direction: Evolution in both the technology and the informatics has been identified as the keys to driving this assay forward. • Pursue multi channel MS technology: MUX • Collaboration with Advanced Chemistry Development (ACD): server based processing suite designed to parse and integrate the MUX data. 052306_uSomes_None_06 0.65

Background: Sample management in the freezer storage is, and will always be, a concern. • Focus on the sample management became a priority. • Better utilize the freezer space and coordinate sample exchange Purpose: To provide a storage management solution that is capable of tracking information pertaining to sample containers through the use of bar-coding: • Location history • Checkout status • Responsible party • Free thaw cycles • Link to BioAnalytical Manager item • Stock solution management; notification when stocks get low. Direction: Future development would include: • Possibly expand the system to include all types of storage locations used for sample and stock solutions.

Figure 10: Spec UI Sample Check-in page

Figure 11: Spec UI Inventory Management page; used for auditing

Background: Currently in the development phase using BD’s Gentest Serum Binding Plate. • Data handling of the development data is time intensive • Plate based analysis lends to long sample lists Purpose: This assay is seen as a crucial analysis tool to be used prior to in vivo studies. Direction: This assay will follow the typical development cycle with validation. Integrating this assay on the MUX platform will greatly increase throughput. • Use workflow management from Solubility Manager • Use data analysis engine from Purity toolkit • Move to full automation and investigation into High Throughput

PAMPA Background: Not deployed as a production assay; in the process of validating technology. • Intense manual manipulation with Excel spreadsheet templates • Development was initiated when the plate was identified and applicable informatics solutions began to emerge.

%

8.78

1.10 7.43

3.26 3.32 1.55

1.00

3.83

4.64

4.78

4.95

5.72 5.92 6.49

6.58 6.82

8.16 7.63

8.41 9.28

9.71

10.24

10.81 11.24

2.28

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

10.00

11.00

Time

Verapamil

Figure 1: Open Access LC/MS Intranet Page

Purpose: The page is open to all users, serving as a public forum for communication. • Helps to reduce the number of hallway conversations and mass emails • Serves as the official downtime record and repair log for the system • Easy access is invaluable during repair troubleshooting • Backpressure monitoring allows for quick assessment of system • Marketed as a primary information tool for allowing synthetic chemists to troubleshoot some of the minor problems, or provide more detailed troubleshooting tickets. Direction: Training for the system via the webpage is being planned. • Method information • Column information • Easy chromatography solutions

Purpose: To produce server generated reports from the data that is uploaded into the various managers. • Homogenized reports to a certain visual format and quick authoring. • The report generator allows a user to Figure 14: Example PDF Report concentrate on the data analysis

Background: To handle the voluminous flow of reports being generated, solutions for document management had to be developed. • Jaws PDF Creator® to create a non-editable final version of the reports. • Acrobat Digital Signatures® on the cover of the reports • SharePoint tools utilized to create a document library • Sitrof Compliance Module for Xerox DocuShare®: auto-PDF capabilities, signatures in the reports and advanced routing capabilities Purpose: To provide a tool for: • Reviewing documents within the different workgroups • Routing for approval • Storage of documents in an organized accessible location

Figure 15: DocuShare Screenshot

Direction: Transition to this system, incorporate all historical data. Drive out-of-the-box solutions to the Analytical Departments workflow: • Use of established document naming nomenclature • Hierarchy routing • Posting of approved reports to SQL database • Association of supporting documents to the approved (e.g. manifests)

Conclusion The success of the Kalypsys® Analytical Chemistry Department’s technological developments will be largely based on its ability to efficiently process and distribute the data the advancements yield. Presentation of the data in a manner that effectively communicates the findings and facilitates lead optimization is crucial. Managing the information becomes burdensome if measures are not taken to employ appropriate data and document solutions. Properly assessing the workflow and producing specifications for desired solutions is critical.

1: TOF MS ES+ TIC 8.87e3

0.71

Verapamil

11

Background: Increase in throughput and subsequent report generation, a solution for producing reports became imperative. • No reason why the system couldn’t construct the report. • Users input free text fields to complement the information • Report generation allows for a capture of the analysis, while providing all the pertinent information surrounding the results.

Xerox DocuShare®

Purpose: PAMPA is being designed to take place after solubility analysis. Service Contact Information

KNET Report Tools

Direction: Drive the report generation capabilities into all the various assay and workflow managers. • Integration with DocuShare®; seamless flow to archives

PPB

Solubility

Background: Purity analysis is performed post HTS as a verification step on the screening hit prior to further assay work. • Results are compiled into a Fractionlynx® report using the integration methods contained within Masslynx®. • UV and ELSD traces are audited by the analyst to check the integration values. • Current usage varies from 60 to 3000 samples analyzed per run.

Feedback (Complaint) Section

REPORT (PDF)

TECAN Purpose: This version will WORKLIST BIOANALYTICAL work to provide files REPORT GENERATOR necessary to prepare and LiHA analyze samples using the DMPK WINNONLIN SAMPLE REPORT PREP technology currently present GENERATOR in the department: LC/MS • LiHA worklists and WORKLIST LC/MS sample lists • Utilize the log files generated from DMPK REPORT LC/MS (PDF) ANALYSIS equipment; processing and analysis errors are accurately captured in Figure 6: Illustration of BioAnalytical the report. Manager v2.0 functions. • Compound requesting • Freezer management integration • Platemap tools and result table generation to assist analyst • WinNonLin® compatibility will allow for easier regression work

Assay Data Handling. • Utilized server based technology to construct powerful assay managers.

Open Access Webpage

Freezer Management

Direction: Take the assay through a similar validation and development plan used on the solubility assay. • Use architecture from Solubility Manager • Assay will be expanded to include multiple pH and lipid configurations. • Move to full automation and investigation into high throughput

Figure 7: Sample results page (from left to right); pass/fail indicator, tabulated results, triplicate spectra, calibration spectra, calibration curve, structure, compound ID, plate barcode, and well location.

One of the key points in the successful collaboration of Analytical Chemistry and Informatics at Kalypsys was the positive open communication that existed between the departments. Written specifications and SOP documents were effective pieces of information used by Informatics to help achieve the design desired by Analytical. Access by Analytical to the development servers to actively test the products in their design state, and producing testing reports, allowed Informatics to build the products more efficiently. Coupled with weekly meetings, these communication strategies produced the success seen in the deliverables.

Acknowledgements The authors would like to thank the following individuals for their input and contributions: Juan Wang, Nahid Yazdani, Jerry Muhammad, Connie Zhao, Devapratim Sarma, and Robert Beltran.

Figure 4: Waters LCT Premier® MUX Mass Spectrometer Figure 5: Instrument trace above, with ACD using CODA algorithm below.

Document Reference

Figure 8: User curate ability in Solubility Manager

Figure 9: Incoming sample queue.

Figure 12: BD PPB Plate

Figure 13: Millipore PAMPA Plate

Product Reference

AC-MethDev-2006-005v1

Solubility

SharePoint®

Microsoft

AC-MethDev-2006-012v1

HT Solubility

SpecManager Suite

ACD

AC-MethDev-2006-014v1

BioA Mgr v2.0

Automation Server

ACD

AC-MethDev-2006-015v2

Freezer

Multiscreen Solubility (MSSLBPC50)

Millipore

AC-MethDev-2006-018v2

DocuShare®

PPB Plate (P/N 453700)

BD Gentest

PAMPA (P/N MAIPN4510)

Millipore

DocuShare®

Xerox®

Sitrof Compliance Module

Sitrof Technologies

Poster Contact Charles Taylor

[email protected]