1) Kalypsys has developed various analytical informatics solutions to improve efficiency and data communication for analytical chemists. These include managers for bioanalytical work, sample storage, report generation, and assay data handling. 2) Further development of these solutions aims to increase automation, throughput and integration across different tools and data sources. This includes improving sample management, report generation from multiple data sources, and transitioning assays like solubility and PAMPA to higher throughput. 3) Effective communication between analytical chemistry and informatics teams, including documentation and testing of informatics solutions, was key to the successful development and implementation of these analytical tools.

1. Abstract BioAnalytical Manager v1.0 BioAnalytical Manager v2.0 Freezer Management KNET Report Tools
The ability for Analytical Chemists to impact the drug discovery process will be
Background: Prior to Informatics solutions: Background: BioAnalytical Manager v1.0 revolutionized the workflow for Background: Sample management in the freezer storage is, and will Background: Increase in throughput and
dictated by their applied informatics tools; which will provide efficiency to their
• BioAnalytical workflow management was performed in meetings, by the department. Rate limiting steps for BioAnalytical work were identified: always be, a concern. subsequent report generation, a solution
workflow and effectiveness in their data communication. Focused Analytical
email and through the use of a project whiteboard. • Human sample • Focus on the sample management became a priority. for producing reports became imperative.
Informatics solutions have been developed by Kalypsys for varying PLATEMAP
• This process was conducive to misinformation, mishandling of study preparation • Better utilize the freezer space and coordinate sample exchange • No reason why the system couldn’t
responsibilities.
analysis and inability to track progress. • Report authoring construct the report.
• Result table generation BIOANALYTICAL Purpose: To provide a storage management solution that is capable of • Users input free text fields to
Open Access Support MANAGER v2.0
Purpose: This manager is the definitive record of Kalypsys BioAnalytical • Freezer sample tracking information pertaining to sample containers through the use of complement the information
Intranet information solution was constructed to act as a repository for all
work, both internal and external. management BIOANALYTICAL
bar-coding: • Report generation allows for a capture
information concerning each system: PLATEMAP REPORT
• It is a resource for tracking analyst assignments
ENGINE
• Location history of the analysis, while providing all the
(PDF)
• system status
• Monitor study progression through the various stages Purpose: This version will TECAN
• Checkout status pertinent information surrounding the
• troubleshooting log
WORKLIST
BIOANALYTICAL
• Document posting for each study (sample receipt, reports, etc.) work to provide files REPORT • Responsible party results.
• standard LC/MS traces which are automatically posted daily GENERATOR
• Built-in email communication allows for updates and notifications necessary to prepare and • Free thaw cycles
• backpressure log
analyze samples using the LiHA
• Link to BioAnalytical Manager item Purpose: To produce server generated
• contact information for all applicable vendors
SAMPLE DMPK WINNONLIN
Direction: Design more active content: technology currently present PREP REPORT
GENERATOR • Stock solution management; notification when stocks get low. reports from the data that is uploaded into
• Passive resource that only accepts in the department: the various managers.
BioAnalytical Workflow Management
information • LiHA worklists and LC/MS
Direction: Future development would include: • Homogenized reports to a certain
• BioAnalytical Analysis, a server-based experiment tracking system, was
WORKLIST
• Generation of files to better automate LC/MS sample lists • Possibly expand the system to include all types of storage locations visual format and quick authoring.
developed to assist communication between the analysts and clients.
the analysis of samples • Utilize the log files used for sample and stock solutions. • The report generator allows a user to
• Mandatory inclusion of demographics and data files has produced a Figure 14: Example PDF Report
• Server based data processing tools generated from DMPK REPORT concentrate on the data analysis
system where workload can be anticipated, and forensic tasks simplified. LC/MS
(PDF)
designed to auto-generate reports equipment; processing ANALYSIS
and analysis errors are Direction: Drive the report generation capabilities into all the various assay
Assay Data Handling.
accurately captured in and workflow managers.
• Utilized server based technology to construct powerful assay managers. Figure 6: Illustration of BioAnalytical
the report. • Integration with DocuShare®; seamless flow to archives
• Compound requesting
Manager v2.0 functions.
Document Management
• Freezer management integration
• The homogenizing solution for the data handling has been the emergence
of auto-generating PDF reports.
• Platemap tools and result table generation to assist analyst Xerox DocuShare®
• WinNonLin® compatibility will allow for easier regression work
• Created by server applications that can be e-signed before distribution.
• Power of producing historical reports with pertinent experimental sections,
Background: To handle the voluminous flow of reports being generated,
Direction: The implementation of the solutions contained in this release solutions for document management had to be developed.
will greatly impact the capacity of work that an analyst will be able to • Jaws PDF Creator® to create a non-editable final version of the reports.
Verapamil perform. • Acrobat Digital Signatures® on the cover of the reports
Open Access Webpage • The introduction of data into the system through this version provides
for a wealth of information to be made available.
Figure 10: Spec UI Sample Check-in page Figure 11: Spec UI Inventory
Management page; used for auditing
• SharePoint tools utilized to create a document library
• Sitrof Compliance Module for Xerox DocuShare®: auto-PDF
Figure 2: Studies arranged in tabs by stage Figure 3: Details page for a study • Implementation of this data into SAR table generation capabilities, signatures in
Background: Utilizing the SharePoint® internet tools provided on the the reports and advanced
Kalypsys® intranet, a system management webpage was created to track routing capabilities
and publish system events. The page evolved to include:
Purity Solubility PPB Purpose: To provide a tool for:
Analytical Support Group Point Person • Reviewing documents
Background: Purity analysis is performed post HTS as a verification step Background: Solubility is performed using the Millipore Multiscreen® Background: Currently in the development phase using BD’s Gentest within the different
on the screening hit prior to further assay work. Solubility Plate. Serum Binding Plate. workgroups
• Results are compiled into a Fractionlynx® report using the integration • Stated throughput for this assay is 28 compounds per week • Data handling of the development data is time intensive • Routing for approval
Automatically posted Standard
methods contained within Masslynx®. • Previous data handling: Excel Macros • Plate based analysis lends to long sample lists • Storage of documents in an
• UV and ELSD traces are audited by the analyst to check the • Solubility Manager deployed; online curate and assay management organized accessible location Figure 15: DocuShare Screenshot
integration values. • Solubility Test Sets are processed by the server into PDF reports. Purpose: This assay is seen as a crucial analysis tool to be used prior to
Daily Backpressure Log in vivo studies.
• Current usage varies from 60 to 3000 samples analyzed per run. Direction: Transition to this system, incorporate all historical data. Drive
Purpose: Solubility is deployed as a post biological screening assay. out-of-the-box solutions to the Analytical Departments workflow:
Purpose: As Kalypsys® has engaged itself in the application of uHTS • The assay is typically used to diagnose problem compounds Direction: This assay will follow the typical development cycle with • Use of established document naming nomenclature
Important Documents technology, the throughput that is necessary to support the hits resulting • Requested for data gathering with little consideration for the results. validation. Integrating this assay on the MUX platform will greatly • Hierarchy routing
from these screens must be optimized: • Needs to be positioned as a mandatory assay increase throughput. • Posting of approved reports to SQL database
• Shorter sample cycle time • Use workflow management from Solubility Manager • Association of supporting documents to the approved (e.g. manifests)
• Automated data processing Direction: To position the assay accordingly in the discovery process it • Use data analysis engine from Purity toolkit
Troubleshooting Log
• Purity during library building for efficiency in the subsequent testing
• Database storage; easy access and data mining capable
must be made cost effective, high throughput and capable of delivering
data that is pertinent to the projects.
• Move to full automation and investigation into High Throughput
Conclusion
System Component Information
• Internet access to plate and sample traces • Kalypsys® has initiated technology development projects
• With Solubility Manager, the individual data is drawn into information
PAMPA The success of the Kalypsys® Analytical Chemistry Department’s technological
developments will be largely based on its ability to efficiently process and
Direction: Evolution in both the technology and the informatics has been engines (i.e. SAR table generator) Background: Not deployed as a production assay; in the process of distribute the data the advancements yield. Presentation of the data in a manner
identified as the keys to driving this assay forward. • Queuing system allows for workflow management
validating technology. that effectively communicates the findings and facilitates lead optimization is
Surveys • Pursue multi channel MS technology: MUX
• Intense manual manipulation with Excel spreadsheet templates
crucial. Managing the information becomes burdensome if measures are not
• Collaboration with Advanced Chemistry Development (ACD): server
• Development was initiated when the plate was identified and taken to employ appropriate data and document solutions. Properly assessing
based processing suite designed to parse and integrate the MUX data. applicable informatics solutions began to emerge. the workflow and producing specifications for desired solutions is critical.
Feedback (Complaint) Section 052306_uSomes_None_06
0.65 0.71
1: TOF MS ES+
TIC
8.87e3
Purpose: PAMPA is being designed to take place after solubility analysis. One of the key points in the successful collaboration of Analytical Chemistry and
Informatics at Kalypsys was the positive open communication that existed
Verapamil
8.78
%
Service Contact Information
1.10
7.43 8.16
Direction: Take the assay through a similar validation and development between the departments. Written specifications and SOP documents were
plan used on the solubility assay.
6.58 6.82 7.63
effective pieces of information used by Informatics to help achieve the design
8.41
5.72 5.92 6.49 9.28 9.71 10.81 11.24
3.26 3.32 3.83 4.64 4.95 10.24
4.78
1.55
2.28
• Use architecture from Solubility Manager
11 Time
desired by Analytical. Access by Analytical to the development servers to
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00
• Assay will be expanded to include multiple pH and lipid configurations.
actively test the products in their design state, and producing testing reports,
Verapamil
Figure 1: Open Access LC/MS Intranet Page • Move to full automation and investigation into high throughput
allowed Informatics to build the products more efficiently. Coupled with weekly
Figure 7: Sample results page (from left to right); pass/fail indicator, tabulated results, meetings, these communication strategies produced the success seen in the
Purpose: The page is open to all users, serving as a public forum for triplicate spectra, calibration spectra, calibration curve, structure, compound ID, plate deliverables.
communication. barcode, and well location.
• Helps to reduce the number of hallway conversations and mass emails
Acknowledgements
• Serves as the official downtime record and repair log for the system
• Easy access is invaluable during repair troubleshooting Figure 4: Waters LCT Premier® MUX The authors would like to thank the following individuals for their input and
• Backpressure monitoring allows for quick assessment of system Mass Spectrometer contributions: Juan Wang, Nahid Yazdani, Jerry Muhammad, Connie Zhao,
• Marketed as a primary information tool for allowing synthetic chemists Devapratim Sarma, and Robert Beltran.
to troubleshoot some of the minor problems, or provide more detailed Figure 5: Instrument trace above, with ACD Document Reference Product Reference
troubleshooting tickets. using CODA algorithm below. 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
Direction: Training for the system via the webpage is being planned. AC-MethDev-2006-015v2 Freezer Multiscreen Solubility (MSSLBPC50) Millipore
• Method information AC-MethDev-2006-018v2 DocuShare® PPB Plate (P/N 453700) BD Gentest
• Column information
PAMPA (P/N MAIPN4510) Millipore
Figure 8: User curate ability Figure 9: Incoming sample queue. Figure 12: BD PPB Plate Figure 13: Millipore PAMPA Plate Poster Contact DocuShare® Xerox®
• Easy chromatography solutions in Solubility Manager Charles Taylor ctaylor@kalypsys.com Sitrof Compliance Module Sitrof Technologies