Genentech PKS case study - Pharsight
Genentech PKS case study - Pharsight
Genentech PKS case study - Pharsight
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Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
3/22/2007<br />
Implementation and Use of<br />
<strong>PKS</strong> at <strong>Genentech</strong>:<br />
A Case Study<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 2 3/22/2007<br />
Agenda<br />
• Project Objectives & Background<br />
• Implementation Teams<br />
• Impact / Efficiency Gains<br />
• Challenges & Lessons Learned<br />
• Future Enhancements<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 3 3/22/2007<br />
Problem Statement<br />
• PK analyses done in WinNonlin do not meet<br />
21CFR.part11 compliance standards<br />
– A procedural work-around is used<br />
• Current PK workflow is time consuming and<br />
error-prone.<br />
– Analyst performs many manual, SOP-specified steps<br />
– QC review ensures consistency of data with report<br />
• There is currently no infrastructure for doing pooled<br />
analysis or data mining.<br />
– Individual data files are archived to a server<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 4 3/22/2007<br />
Project Objectives<br />
• To implement a computer system and<br />
procedures for doing PK and/or PD<br />
analyses at <strong>Genentech</strong> that are<br />
21CFR.part11 compliant.<br />
• To deliver a database and additional tools<br />
for improving clinical and nonclinical data<br />
analysis workflow and reporting<br />
• To develop a data warehouse with the ability<br />
to perform queries and meta-analyses<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 5 3/22/2007<br />
Scope of the project<br />
• Approximately 60 users in 2 departments<br />
– PKPDS and DMPK departments<br />
• Source data from 2 data sources<br />
– Watson LIMS<br />
– SPA created SAS-transport file (merged from Watson LIMS & Oracle Clinical)<br />
• The initial phase of the project consists of:<br />
– WinNonlin v5.1.1 upgrade<br />
– <strong>PKS</strong> database v3.1<br />
– Clinical and nonclinical connectors<br />
– All associated processes – validation, SOPs, training, etc.<br />
– SMDI and Clinical Views<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 6 3/22/2007<br />
Data flow architecture using <strong>PKS</strong><br />
CRO data<br />
Oracle Clinical<br />
DMPK Watson<br />
WatsonLIMS<br />
SAS transport file<br />
DMPK<br />
Connector<br />
Nonclinical<br />
Connector<br />
SMDI –<br />
small molecule<br />
discovery<br />
studies<br />
Clinical<br />
Connector<br />
P<br />
K<br />
S<br />
Database<br />
with<br />
Conc,<br />
Dosing<br />
and<br />
PK<br />
Parms.<br />
WinNonlin<br />
Auto Pilot<br />
<strong>PKS</strong> Clients<br />
<strong>PKS</strong> Reporter<br />
Clinical data<br />
back to SPA<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 7 3/22/2007<br />
Benefits of the “New” Process w/ <strong>PKS</strong><br />
• Data transferred directly to <strong>PKS</strong> from Watson & SPA<br />
– Base scenarios as a starting point of PK Analyses<br />
• PK Data Analysis and QC processes are streamlined<br />
– Maximize the use of <strong>PKS</strong> and WinNonlin functions to improve compliance<br />
– Table wizard, BLQ wizard, Multi-transform tool, and Audit Trails<br />
– Naming conventions for analysis to be used for regulatory filings (e.g., interim<br />
and final scenarios)<br />
• <strong>PKS</strong> is the system of record for PK related data<br />
– PK data no longer archived to stand-alone servers<br />
– All PK data and supporting documents are stored in <strong>PKS</strong><br />
–Tables, graphs, images, protocols, etc. are associated with the appropriate scenarios<br />
–Facilitates implementation of a PK data warehouse<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 8 3/22/2007<br />
Implementation Process Overview<br />
• Gap analysis<br />
• Vendor demos<br />
• User Req & Functional Specs<br />
• Connector Development<br />
• Process Workflow & Configuration Decisions<br />
• SOPs<br />
• Validation & Testing<br />
• Training<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 9 3/22/2007<br />
Implementation – Core Team<br />
• Core Team representation<br />
– Team leaders (Business and DevIT)<br />
– Project Manager<br />
– Compliance Manager<br />
– PK Scientist<br />
– DevIT programmer<br />
• Core Team deliverables<br />
– User Requirements & Functional Specifications<br />
– Impact assessment on business practices<br />
– All SOPs<br />
– Training<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 10 3/22/2007<br />
Business Process Team<br />
• Business Process Team representation<br />
– Same as Core Team plus the following:<br />
– 3 clinical PK scientist<br />
– 3 nonclinical PK scientist<br />
• Business Process Team Deliverables<br />
– All aspects of Process Workflow for both clinical and nonclinical<br />
– from raw data to report finalization<br />
– All meta-data, <strong>study</strong> attributes and custom attributes<br />
– Configuration decisions<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 11 3/22/2007<br />
Connector Development Team<br />
• Connector Development Team representation<br />
– Team Leader<br />
– Nonclinical Sample Handling (nonclinical connector)<br />
– Statistical Programmer (clinical connector)<br />
– PK Scientist<br />
– DevIT Programmer<br />
– <strong>Pharsight</strong> Programmer<br />
• Connector Development Team Deliverables<br />
– Variable & parameter standardization<br />
– Connector specifications development<br />
– Iterative testing / fixing cycle<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 12 3/22/2007<br />
Validation Team<br />
• Validation Team representation<br />
– Validation Manager<br />
– Validation Lead<br />
– 2 Validation Specialists<br />
• Validation Team Deliverables<br />
– System Assessment Document<br />
– User Requirements Document<br />
– Functional Specifications Document<br />
– Installation & Configuration Documents<br />
– Validation Protocol (IQ/OQ/PQ)<br />
– Validation Summary<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 13 3/22/2007<br />
Things that went well<br />
• Good, active, cross-functional team.<br />
• Team committed to timeline (later in the project.)<br />
• Good Management Support<br />
• Good catch-up efforts for resetting the project<br />
• <strong>Pharsight</strong> Workshop was very helpful<br />
• Driven Managers<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 14 3/22/2007<br />
Challenges during development<br />
• New Project Manager hired in March ’06<br />
– Caused delays and pushed back our “go live” date<br />
• Connector development was more time consuming<br />
than expected<br />
– Iterative process with vendor to identify, fix and test bugs<br />
– Late changes to connector specs caused additional work<br />
– “test” datasets need to be mocked-up to fully test clinical connector<br />
– Nonclinical connector changed to support dosing data in Watson<br />
• “To Be” process needed to balance all business<br />
aspects<br />
– Changes in PKPDB, DMPK processes; and other upstream/downstream<br />
processes like SMDI, Sample Handling, etc.<br />
– Future data mining needs, e.g., across studies, species, etc<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 15 3/22/2007<br />
Challenges post-deployment<br />
• <strong>PKS</strong> learning curve<br />
– User resistance to using new PK analysis tools and workflow processes<br />
– New users often require 1:1 mentoring with more experienced <strong>PKS</strong> users<br />
• <strong>PKS</strong> not currently used for all types of PK analysis<br />
– Currently only required for Watson LIMS data analyzed in WinNonlin<br />
– Requires two process workflows, SOPs, training, etc.<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 16 3/22/2007<br />
Lessons Learned<br />
• Project Charter<br />
– Important initiation deliverables to be defined at the beginning of the project<br />
– Project Charters, Communication plan, Roles and Responsibility matrix, etc.<br />
– Need to convey the meaning and the purpose of this to the team members<br />
and get a complete buy-in from them<br />
• Variable levels of participation during the project<br />
– Large time investment for Core & Business Process Team members<br />
– Lack of participation from other groups during the initiation process<br />
– e.g. Dev IT not involved in evaluating and selecting solution options<br />
– Difficulty in getting GLP/QA to participate.<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 17 3/22/2007<br />
Lessons Learned (continued)<br />
• Technical Development<br />
– Underestimated complexity of connectors needed for <strong>PKS</strong>, which took longer<br />
to create than the time allocated in the original schedule.<br />
– We need to have more experienced subject matter experts on team.<br />
• Project Plan<br />
– Underestimation of time required for respective tasks which lead to a resource<br />
crunch and difficulty in delivering on time.<br />
– There is a need for a detailed Project Plan which covers a realistic project<br />
timeline and conveys 3 key concepts to the team members.<br />
–Roles and Responsibilities Matrix<br />
–Communication Plan<br />
–Critical Path of the Project<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 18 3/22/2007<br />
Lessons Learned (continued)<br />
• Resources<br />
– Insufficient resources (e.g. Business Analyst, Subject Matter Experts) caused<br />
some delay in the deliverables.<br />
– Communication and commitment of resources from all cross functional groups<br />
(Functional Managers) involved in the project was somewhat lacking.<br />
– It was difficult to understand external resources Roles & Responsibilities.<br />
• Training<br />
– Validation Training (GDP, OQ, PQ execution) – Identify users who have<br />
executed in the past, train early, allow time to practice and understand the<br />
process.<br />
– Training members with <strong>PKS</strong> very early on would have helped.<br />
– Not just give an overview<br />
– Have some internal RAs or Scientists as trainers or ‘super users’.<br />
– Utilize the “Learning and Development Solutions” department early on.<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 19 3/22/2007<br />
Lessons Learned (continued)<br />
• Validation<br />
– Need pro-active involvement of the Validation Group to avoid lots of rework.<br />
– Business side needs to understand validation concepts more clearly.<br />
– A full overall picture was lacking for everyone, which lead to validation<br />
challenges.<br />
– Multiple Dry runs (PQ) and Test Scripts (PQ) were ambiguous, which lead to<br />
failed test scripts and more dry runs.<br />
– PQ testers oversights lead to errors.<br />
– not reading the test script, misreading the test script and deviations<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 20 3/22/2007<br />
Future enhancement plans<br />
• Expand functionality by adding other components of<br />
the <strong>PKS</strong> suite of applications<br />
– Auto-Pilot, <strong>PKS</strong> Reporter and <strong>PKS</strong> clients<br />
• Expand the scope of PK analysis done in the <strong>PKS</strong><br />
system<br />
– Population PK, Pharmacodynamics, etc.<br />
– Import data from other non-standard sources<br />
• Utilize <strong>PKS</strong> as a Data Warehouse<br />
– Make use of <strong>study</strong> attributes and custom attributes to do data mi ning<br />
– Create pooled and merged datasets in <strong>PKS</strong> for analysis<br />
© 2005, <strong>Genentech</strong>
Implementation and Use of <strong>PKS</strong><br />
at <strong>Genentech</strong>: A Case Study<br />
Slide 21 3/22/2007<br />
PKDMAS Team<br />
PKPDS<br />
• Steve Eppler<br />
• Nicolas Pelletier<br />
• Dan Combs<br />
• Joshua Haznedar<br />
• Doug Leipold<br />
• Saileta Prabhu<br />
• David Allison<br />
• Song Ren<br />
• Banmeet Anand<br />
• Brendan Bender<br />
• Mingxin Qian<br />
• Don Sinclair<br />
• Lu Xu<br />
• Jie Ling<br />
• Deborah Mortensen<br />
• Arthur Reyes<br />
• Eric Stefanich<br />
• Maya Leabman<br />
DMPK<br />
• Harvey Wong<br />
• Hank La<br />
• Jodie Pang<br />
• Joe Feng<br />
• Jacob Chen<br />
• Jason Boggs<br />
• Bianca Liederer<br />
Bioanalytical<br />
Assays<br />
• Chris Morrow<br />
Chemoinformatics<br />
• Kevin P. Clark<br />
SPA<br />
• Nick Paszty<br />
• Marc Drucker<br />
• Lisa Price<br />
Sample Handling<br />
• Tim Nuhring<br />
• Shawn Ralston<br />
GLP / QA<br />
• Cora Lai<br />
• Robin Stewertson<br />
CIT<br />
• Grace Yuan<br />
DevIS<br />
• Jon Sasano<br />
• Sanjeev Bindra<br />
• Nirmala Bandrapalli<br />
• Jerome Rainey<br />
• Ritu Dhawan<br />
• Suki Hyare<br />
• Dileep Cherukuru<br />
• Todd Wierzbowski<br />
• Thanda Lee<br />
• Nilesh Narayan<br />
• Floyd Stone<br />
• Praful Desai<br />
<strong>Pharsight</strong><br />
• Ana Henry<br />
• Erin Guinan<br />
© 2005, <strong>Genentech</strong>