Preclinical development in the current Pharmaceutical space

©2016 IDBS, Confidential

Preclinical Development

Dr. Paul Denny-GouldsonVP, Strategic SolutionsIDBS


Wherever you want to go,key drivers will influence your route…

Accelerated innovation – and more of it

Products to market faster Improved margins


CMC

A Strategic vision and SolutionIntegrated R&D&O Data, Process and Knowledge Management for Pharma

Process Chemistry

& Isotope

Production

Formulation

(GxP)

Analytical Dev

& Stab Testing

(GxP)BioAnalysis

(GLP)

Metabolite ID

Material

Sciences

Pharmacology &

Safety

PKPD

Pharmacokinetics

Drug Metabolism

Pilot

Manufacturing

QA/QCLead

Optimization

Target ID and

Mechanism

Lead ID and Med

Chem

DevelopmentManufacturing

Disease Pathways OperationsResearch


An IDBS Preclinical SolutionIntegrated preclinical development Data and Knowledge Management environment

Process

Chemistry &

Isotope

Production

Formulation

(GLP)

Analytical &

Stability

Testing (GLP)BioAnalysis

(GLP)

Metabolite

ID

Material

Sciences

Pharmacology

& Safety

PKPD

Pharmacokinetics

Drug

Metabolism


The goal is to build an R&D data value chain

5


Master Request

List (Excel)

Drug Metabolism – Current State

Test Request

Sequence(Text)

Customer Assay Testing Lab

Instrument

Test RequestTest

RequestTest Request

Assay Setup (Excel)

Analysis(Stats

Package)

Summary(Excel)

Compound Details

Data Warehouse

Queries

Report

Report

ReportReport

Manual sequence creation

Copy & paste data; manual

analysis

Manually load data to

warehouse

Manually split data into separate reports

by project or customer

Email

Email

Communication done predominantly by email & sending files

Fetching compound

detailsOptimizing assay usage by

combining multiple requests

Manual Step: Copy & Paste or

Email


Drug Metabolism – Streamlined Workflow

Test Request

Customer Assay Testing Lab

Instrument

Test RequestTest

RequestTest Request

IDBS Assay Record

(from template)

Compound Details

Data Warehouse

Queries

Report

Report

ReportReport

Automated data load and

analysis

Automated loading of results to warehouse

on publishing

Communication is orchestrated through task system: allowing alerts,

emails, scheduling and updates

Direct integration with inventory

Support for splitting or combining requests and assigning compounds to specific tests

Master Request Queue

Queries

Data reported by project/customer or other means

using queries and automated reports

Assay Parameters

Sequence

Data

Analysis & Results

Automated sequence creation


Some examples of what people already do

Class Assay/Workflow

Pharmacokinetics Study DesignDosing and Sample CollectionSolution/Standards PreparationWorklist and Instrument InterfacingNon-Compartmental AnalysisCassette StudiesTissue Uptake

Inhibition CYPTDI ScreenBCRPPGP MRP-2reversible/irreversible

Induction Hepatocytein vitro, ex vivoRGA/PXR

Stability Hepatocyteliver microsomesrCYP

Class Assay/Workflow

Metabolic ID Completein vitroIn vitro HTanimal ADMEhuman ADME

Transport/Uptake OATB-ClearCACOMDCK-PCRPKi determinationKm/Vmaxunidirection/bidirectional

Solubility

Protein Binding Covalent Bindingadduct formationEquilibrium dialysis

Blood:Plasma Ratio


Pharmacokinetics – Current State

Test Request

Study Plan (Word)

Test Request

Sample Collection

(Excel)

Sequence(Excel/Text)

CustomerAnimal

TechnicianStudy

Director Bio analyst

Mass Spec

Report (Word)

QA

Analysis is done by hand or copied to/from external

application

Manual sequence creation

Email

Email

Email EmailEmail

Communication done predominantly by email & sending files

Content in report must be traced back

to source records

Report is manually created from results file Analysis

(Excel/WNL)


Email


Pharmacokinetics – Streamlined Workflow

Test Request

Study Plan

Sample Collection Sequence

Customer Animal Technician

Study Director Bioanalyst

Mass Spec

AnalysisReport (Word)

QA

Data is imported and analysis is automatically

completed

Query

Optimized sequence is generated by query for

samples associated with study

Query

Tasks

Communication is orchestrated through task system: allowing alerts,

emails, scheduling and updates

Review is minimal as analysis and report are

system generated. Approval tracked using

task system

Word Report is generated automatically using

Export to Word features

Query

Optimized dosing and sampling schedule

automatically created after querying system

for study plan info

Test Request


PKPD Challenges

Results from different experiments/assays to be easily

queried and rapidly combined for meta analysis and/or trending

Coordinating PK and PD studies can be tough!

Merging datasets is time consuming and error prone

PKPD throughput is constrained


PKPD – Current StateEfficacy (PD) Study

Collect Samples

Bioanalysis (PK) Study

Import Sample Information

Collect Measurement

DataCollect PK Data

Send PK Request

Sample Info

Create ReportPK

ResultsCreate Report

Load data to warehouse

PKPD Modeler

Merge PD+PK data per sample

Massage data to load into modeling

tool (e.g. NONMEM)


Email

Requests are sent, typically via email, often with incomplete

information

Data are reported in multiple formats often

without full sample information

Summary reports are manually

created in Word, Excel or PPT Report

Manually load data to

warehouse

Merging the data and preparing it for analysis is by hand. Very time consuming

and error prone


Efficacy (PD) Study Bioanalysis (PK) Study

PKPD Modeler

PKPD – Streamlined Workflow

Collect Samples Import Sample Information

Collect Measurement

dataCollect PK data

Send PK Request

Sample Info

Create ReportPK

ResultsCreate Report

Merge PD+PK data per sample

Massage data to load into modeling

tool (e.g. NONMEM)

Test Requesting orchestrates requesting and scheduling

process

Data can be transmitted via the

database and retrieved using a query

Data can be easily merged with a query,

reducing errors

Summary reports can be automatically

generatedReport

Data can be analyzed/visualized within the system automatically, or

formatted ready for export

Key results can be automatically loaded to data

warehouse




14

Bioanalysis - Going beyond the basics Insight into what else IDBS can provide as part of a BA solution

• Watson / No Watson?

• Reagents• Equipment• Deviation Management


Certificate of Analysis

Registration of critical COA related data.

pH Meter CalibrationpH Meter Calibration data

management.

Matrix LotRegistration of Matrices and

management of pooling information.

Standard and QC PrepTracking of relevant

information from preparation of Standards and QCs.

Common ReagentTracking of relevant

information from preparation of common

reagents.

Stock SolutionTracking of relevant

information from stock solution

creation.

Balance CheckProcess to ensure

balances function within expected limits.

Sample AnalysisCollection of analytical run

related data from production, method

validation, qualification or mandatory repeat runs.

Sample HandlingManage the logistics around registering

sample handling, sample shipment discrepancies and sample disposal.

Bioanalysis – the bit not in a LIMS


Formulations challenges Have we made this before – I cannot find any information on a given

formulation as all the data is in excel / local databases What was done to this formulation compared to another one – we want to

reduce the amount of repeat work and testing of known failed formulations Can we correlate the change in formulation with a change in property – link

downstream testing data with a formulation GLP and non GLP means I have to track everything and in paper it is really

difficult Sharing data with other groups – PK need to know stuff as do analytical but

I spend all my time writing reports and re-working data


An IDBS Preclinical SolutionIntegrated preclinical development Data and Knowledge Management environment

Process

Chemistry &

Isotope

Production

Formulation

(GLP)

Analytical &

Stability

Testing (GLP)BioAnalysis

(GLP)

Metabolite

ID

Material

Sciences

Pharmacology

& Safety

PKPD

Pharmacokinetics

Drug

Metabolism


But - What else is happening in the market Constant pressure on preclinical to be more efficient and

productive

Outsourcing / externalization of preclinical work is growing

But the requirements for accessible and good data is always there


CRO 1

CRO 2

CRO 3

CRO 4

Internal

InternalInternal

Internal

Internal



Why IDBS? Domain Experience

Company What we doUS Pharma IDBS (Global) PK,PD,BT,BA, Pre Formulations

Japanese Pharma IDBS (Global) PKUS Pharma IDBS (Global) PK,PD,BA

EU/US Pharma IDBS (Global) PD, DM, PK, BA, Pre Formulations, GLPUS Pharma IDBS PK

EU/US Pharma IDBS (Global) PD, DM, PK, BA, Pre Formulations, GLPEU Pharma IDBS (Global) PK, BA GLPEU Pharma IDBS BA GLP

US CRO IDBS BA, GLPUS Pharma Global Research and Pre ClinicalUS Pharma DM, PK

EU/US Pharma Oncology Vitro + VivoUS CRO IDBS (BioA, PK)


For further information view our website: www.idbs.com or email: [email protected]

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