Genentech PKS case study - Pharsight

Implementation and Use of PKS 

at Genentech: A Case Study 

3/22/2007 

Implementation and Use of 

PKS at Genentech: 

A Case Study 

© 2005, Genentech



Slide 2 3/22/2007 

Agenda 

• Project Objectives & Background 

• Implementation Teams 

• Impact / Efficiency Gains 

• Challenges & Lessons Learned 

• Future Enhancements 




Slide 3 3/22/2007 

Problem Statement 

• PK analyses done in WinNonlin do not meet 

21CFR.part11 compliance standards 

– A procedural work-around is used 

• Current PK workflow is time consuming and 

error-prone. 

– Analyst performs many manual, SOP-specified steps 

– QC review ensures consistency of data with report 

• There is currently no infrastructure for doing pooled 

analysis or data mining. 

– Individual data files are archived to a server 




Slide 4 3/22/2007 

Project Objectives 

• To implement a computer system and 

procedures for doing PK and/or PD 

analyses at Genentech that are 

21CFR.part11 compliant. 

• To deliver a database and additional tools 

for improving clinical and nonclinical data 

analysis workflow and reporting 

• To develop a data warehouse with the ability 

to perform queries and meta-analyses 




Slide 5 3/22/2007 

Scope of the project 

• Approximately 60 users in 2 departments 

– PKPDS and DMPK departments 

• Source data from 2 data sources 

– Watson LIMS 

– SPA created SAS-transport file (merged from Watson LIMS & Oracle Clinical) 

• The initial phase of the project consists of: 

– WinNonlin v5.1.1 upgrade 

– PKS database v3.1 

– Clinical and nonclinical connectors 

– All associated processes – validation, SOPs, training, etc. 

– SMDI and Clinical Views 




Slide 6 3/22/2007 

Data flow architecture using PKS 

CRO data 

Oracle Clinical 

DMPK Watson 

WatsonLIMS 

SAS transport file 

DMPK 

Connector 

Nonclinical 

Connector 

SMDI – 

small molecule 

discovery 

studies 

Clinical 

Connector 

P 

K 

S 

Database 

with 

Conc, 

Dosing 

and 

PK 

Parms. 

WinNonlin 

Auto Pilot 

PKS Clients 

PKS Reporter 

Clinical data 

back to SPA 




Slide 7 3/22/2007 

Benefits of the “New” Process w/ PKS 

• Data transferred directly to PKS from Watson & SPA 

– Base scenarios as a starting point of PK Analyses 

• PK Data Analysis and QC processes are streamlined 

– Maximize the use of PKS and WinNonlin functions to improve compliance 

– Table wizard, BLQ wizard, Multi-transform tool, and Audit Trails 

– Naming conventions for analysis to be used for regulatory filings (e.g., interim 

and final scenarios) 

• PKS is the system of record for PK related data 

– PK data no longer archived to stand-alone servers 

– All PK data and supporting documents are stored in PKS 

–Tables, graphs, images, protocols, etc. are associated with the appropriate scenarios 

–Facilitates implementation of a PK data warehouse 




Slide 8 3/22/2007 

Implementation Process Overview 

• Gap analysis 

• Vendor demos 

• User Req & Functional Specs 

• Connector Development 

• Process Workflow & Configuration Decisions 

• SOPs 

• Validation & Testing 

• Training 




Slide 9 3/22/2007 

Implementation – Core Team 

• Core Team representation 

– Team leaders (Business and DevIT) 

– Project Manager 

– Compliance Manager 

– PK Scientist 

– DevIT programmer 

• Core Team deliverables 

– User Requirements & Functional Specifications 

– Impact assessment on business practices 

– All SOPs 

– Training 




Slide 10 3/22/2007 

Business Process Team 

• Business Process Team representation 

– Same as Core Team plus the following: 

– 3 clinical PK scientist 

– 3 nonclinical PK scientist 

• Business Process Team Deliverables 

– All aspects of Process Workflow for both clinical and nonclinical 

– from raw data to report finalization 

– All meta-data, study attributes and custom attributes 

– Configuration decisions 




Slide 11 3/22/2007 

Connector Development Team 

• Connector Development Team representation 

– Team Leader 

– Nonclinical Sample Handling (nonclinical connector) 

– Statistical Programmer (clinical connector) 

– PK Scientist 

– DevIT Programmer 

– Pharsight Programmer 

• Connector Development Team Deliverables 

– Variable & parameter standardization 

– Connector specifications development 

– Iterative testing / fixing cycle 




Slide 12 3/22/2007 

Validation Team 

• Validation Team representation 

– Validation Manager 

– Validation Lead 

– 2 Validation Specialists 

• Validation Team Deliverables 

– System Assessment Document 

– User Requirements Document 

– Functional Specifications Document 

– Installation & Configuration Documents 

– Validation Protocol (IQ/OQ/PQ) 

– Validation Summary 




Slide 13 3/22/2007 

Things that went well 

• Good, active, cross-functional team. 

• Team committed to timeline (later in the project.) 

• Good Management Support 

• Good catch-up efforts for resetting the project 

• Pharsight Workshop was very helpful 

• Driven Managers 




Slide 14 3/22/2007 

Challenges during development 

• New Project Manager hired in March ’06 

– Caused delays and pushed back our “go live” date 

• Connector development was more time consuming 

than expected 

– Iterative process with vendor to identify, fix and test bugs 

– Late changes to connector specs caused additional work 

– “test” datasets need to be mocked-up to fully test clinical connector 

– Nonclinical connector changed to support dosing data in Watson 

• “To Be” process needed to balance all business 

aspects 

– Changes in PKPDB, DMPK processes; and other upstream/downstream 

processes like SMDI, Sample Handling, etc. 

– Future data mining needs, e.g., across studies, species, etc 




Slide 15 3/22/2007 

Challenges post-deployment 

• PKS learning curve 

– User resistance to using new PK analysis tools and workflow processes 

– New users often require 1:1 mentoring with more experienced PKS users 

• PKS not currently used for all types of PK analysis 

– Currently only required for Watson LIMS data analyzed in WinNonlin 

– Requires two process workflows, SOPs, training, etc. 




Slide 16 3/22/2007 

Lessons Learned 

• Project Charter 

– Important initiation deliverables to be defined at the beginning of the project 

– Project Charters, Communication plan, Roles and Responsibility matrix, etc. 

– Need to convey the meaning and the purpose of this to the team members 

and get a complete buy-in from them 

• Variable levels of participation during the project 

– Large time investment for Core & Business Process Team members 

– Lack of participation from other groups during the initiation process 

– e.g. Dev IT not involved in evaluating and selecting solution options 

– Difficulty in getting GLP/QA to participate. 




Slide 17 3/22/2007 

Lessons Learned (continued) 

• Technical Development 

– Underestimated complexity of connectors needed for PKS, which took longer 

to create than the time allocated in the original schedule. 

– We need to have more experienced subject matter experts on team. 

• Project Plan 

– Underestimation of time required for respective tasks which lead to a resource 

crunch and difficulty in delivering on time. 

– There is a need for a detailed Project Plan which covers a realistic project 

timeline and conveys 3 key concepts to the team members. 

–Roles and Responsibilities Matrix 

–Communication Plan 

–Critical Path of the Project 




Slide 18 3/22/2007 


• Resources 

– Insufficient resources (e.g. Business Analyst, Subject Matter Experts) caused 

some delay in the deliverables. 

– Communication and commitment of resources from all cross functional groups 

(Functional Managers) involved in the project was somewhat lacking. 

– It was difficult to understand external resources Roles & Responsibilities. 

• Training 

– Validation Training (GDP, OQ, PQ execution) – Identify users who have 

executed in the past, train early, allow time to practice and understand the 

process. 

– Training members with PKS very early on would have helped. 

– Not just give an overview 

– Have some internal RAs or Scientists as trainers or ‘super users’. 

– Utilize the “Learning and Development Solutions” department early on. 




Slide 19 3/22/2007 


• Validation 

– Need pro-active involvement of the Validation Group to avoid lots of rework. 

– Business side needs to understand validation concepts more clearly. 

– A full overall picture was lacking for everyone, which lead to validation 

challenges. 

– Multiple Dry runs (PQ) and Test Scripts (PQ) were ambiguous, which lead to 

failed test scripts and more dry runs. 

– PQ testers oversights lead to errors. 

– not reading the test script, misreading the test script and deviations 




Slide 20 3/22/2007 

Future enhancement plans 

• Expand functionality by adding other components of 

the PKS suite of applications 

– Auto-Pilot, PKS Reporter and PKS clients 

• Expand the scope of PK analysis done in the PKS 

system 

– Population PK, Pharmacodynamics, etc. 

– Import data from other non-standard sources 

• Utilize PKS as a Data Warehouse 

– Make use of study attributes and custom attributes to do data mi ning 

– Create pooled and merged datasets in PKS for analysis 




Slide 21 3/22/2007 

PKDMAS Team 

PKPDS 

• Steve Eppler 

• Nicolas Pelletier 

• Dan Combs 

• Joshua Haznedar 

• Doug Leipold 

• Saileta Prabhu 

• David Allison 

• Song Ren 

• Banmeet Anand 

• Brendan Bender 

• Mingxin Qian 

• Don Sinclair 

• Lu Xu 

• Jie Ling 

• Deborah Mortensen 

• Arthur Reyes 

• Eric Stefanich 

• Maya Leabman 

DMPK 

• Harvey Wong 

• Hank La 

• Jodie Pang 

• Joe Feng 

• Jacob Chen 

• Jason Boggs 

• Bianca Liederer 

Bioanalytical 

Assays 

• Chris Morrow 

Chemoinformatics 

• Kevin P. Clark 

SPA 

• Nick Paszty 

• Marc Drucker 

• Lisa Price 

Sample Handling 

• Tim Nuhring 

• Shawn Ralston 

GLP / QA 

• Cora Lai 

• Robin Stewertson 

CIT 

• Grace Yuan 

DevIS 

• Jon Sasano 

• Sanjeev Bindra 

• Nirmala Bandrapalli 

• Jerome Rainey 

• Ritu Dhawan 

• Suki Hyare 

• Dileep Cherukuru 

• Todd Wierzbowski 

• Thanda Lee 

• Nilesh Narayan 

• Floyd Stone 

• Praful Desai 

Pharsight 

• Ana Henry 

• Erin Guinan

Genentech PKS case study - Pharsight

Create successful ePaper yourself

Delete template?

Save as template?