Adjusting Information Flow from In House HTS to

Global Outsourcing Partners.

Brian BissettPfizer Inc. Groton CT

Structural and Automation Sciences

Overview HTS/DASH Work Flow Outsourcing Modifications

Molecular Properties (Solubility, LogD, etc.) ADME Screens

Data Transfer Serv U File Server

Data Formatting Desktop Java J2EE Applications

Data Uploading Bioloader

Data Viewing RGATE (Research Gateway)

Future FTP Application Excel VBA Based Marshallsoft FTP Component http://www.marshallsoft.com/

Reality Despite dramatically increasing expenditures

for in-house pharmaceutical research and development (R&D) at major drug companies, few internally discovered, breakthrough products are on the horizon.

The pharmaceutical industry's R&D expenditures doubled over the past decade, but new molecular entity approvals plummeted by more than 50%. Source: Cutting Edge Information.

As a result of the changing landscape in the pharmaceutical industry, there will continue to be considerable consolidation and restructuring within the industry.Transformational Disruption in the Pharmaceutical Industry - Jeffrey Leiden, M.D., Ph.D. Clarus Ventures

Consequences

Workflow

Global View of Groton Sample Logistics

Sample Logistics

TA Chemistry

QC & QQC (ACSL)

Liquid Storage (COE)

Local Cmpd Storage

ACSL Purification

Cambridge, WuXi,

ChemBiotech

Dry Store

TA Biology (screening)

Others – PDM

EMS Biology

SND, STL, LJ

Compound Flow to Screens

Sample Logistics

Liquid 30 mM Stock

REMP Plate

4 mM; 2ul or 10 uL

Dry Power

Assay Ready Plates

DASH Plates

(30 or 4 mM, >2uL)

TO

SH

IPP

ING

TO SCREENS

TO

SH

IPP

ING

TO SCREENS

The Traditional Model Structure-based design Computational Chemistry Combinatorial Chemistry

Idea

To Chemistry

Synthesis & Purification

Screening

DB

To Users

The Brave New World Model

Ohio

China

India

Idea

Synthesis & Purification

Screening

DBTo Users

Serv-U File Server

Serv-U Top Level Screen Specific

The Top Level of the File Server has a Directory for each type of Screen that is Outsourced.

Currently: LogD Solubility

Future: pKa & Stability

Serv-U Screen Specific Data

Plates = Information we Send to Analiza Results = Information Analiza Sends to Pfizer Special = Special Studies

Special Study Files may not conform to agreed upon standards and may require special intervention to process and load.

Desktop Java Application Formats Data

User Selects appropriate plate from drop down menu

Files are then reformatted with proper headers and made compliant with the Pfizer Bioloader Application.

File Changes are Tracked and Logged

Each Reformatted File Processed Creates a log file which indicates changes made and any errors that occurred during reprocessing.

Loading Data - BioLoader

Web based tool for Assay Data Loading. Same tool Utilized at all sites for all screens.

BioLoader Screen Selection

Any properly registered Screen can load data using Bioloader.

Users have access to screens based on their specific needs.

BioLoader Main Screen

Shows Data Loaded and Data Pending to Load

The Loading Process – User Feedback

A Successful Data Load

Getting Results - Research Gateway

RGATE – Select Screen(s) to Query Computational

Screens require much longer computing times. ACD Labs, Tripos, etc.

Multiple screens and parameters may be queried at once.

RGATE – Query Methods

Running RGATE Query Some

Queries take hours or even days to run.

Time depends on number of CP’s to be returned and computing required.

RGATE – Report Creation from DB

Automated FTP File Processing Processing the files that come back from

Analiza is a very time consuming process. Plate Files and Result Files must first be

matched. The files must then be processed to form a

Results File which can be uploaded using the Bioloader Tool.

The processed Results Files must then be manually uploaded to the Oracle DB using the Bioloader Tool.

A log must be manually kept which records the last Plate and Results files that were processed, so the starting point is known the next time the process is run.

The processed plates need to be compared against the plates shipped so to guard against the possibility that compounds were lost.

Automated FTP File Processing

What we have Accomplished Plate Files and Result Files must first be

matched. The files must then be processed to form a

Results File which can be uploaded using the Bioloader Tool.

A log must be manually kept which records the last Plate and Results files that were processed, so the starting point is known the next time the process is run.

The processed plates need to be compared against the plates shipped so to guard against the possibility that compounds were lost.

The processed Results Files must then be automatically uploaded to the Oracle DB using the Bioloader Tool.

Additional ResourcesPractical Pharmaceutical

Laboratory Automation Hardcover: 464 pages Publisher: CRC Press (May 2003) ISBN: 0849318149

Automated Data Analysis with Excel

Softcover: 442 Pages Chapman & Hall (June 2007) ISBN: 1-58488-885-7

AcknowledgementsMarina Shalaeva

Scientist - Molecular Properties Group

Tatyana DoroshenkoData Manager - Therapeutic Area Scientific Information Services (TASIS)

Dr. Alex Yanovsky Associate Research Fellow - Oncology Medicinal Chemistry

Dr. Laurence PhilippeAssociate Research Fellow - Analytic and Sample Logistics

George PerkinsAssociate Research Fellow - Structural and Automation Sciences

Aimee N. KestranekAnaliza - Director of Analytical Services