Later-Stage Development: Ensuring Compliance During. for a Competitive Advantage Webinar Series

Transcription

1 Part II: Later-Stage Development: Ensuring Compliance During Clinical i l Trials Process Driven Compliance for a Competitive Advantage Webinar Series 29 September 2010

2 Process Driven Compliance Webinar Series Aligning business process with regulatory requirements to accelerate product performance in the new era of regulatory enforcement Webinar #1 Webinar #2 Webinar #3 Sept 9 Sept 29 Oct 20 Aligning Regulatory Compliance with Optimized Business Processes Development: Ensuring Compliance During Clinical Trials Thriving in the FDA's New Reign of Enforcement R&D Later Stage Post Marketing 2

3 Agenda Introductions Changes in the Clinical Trial Environment Industry and Novartis QA Perspectives on Management of Clinical Development Partners Lilly Model for Management of Third Party Organizations in Clinical Research Model Process for Regulatory Compliance Oversight Q&A Close 3

4 Michael Swiatocha Practice Leader, R&D Compliance and Bioresearch Monitoring Quintiles Consulting Extensive expertise designing and implementing regulatory compliance and risk management programs for emerging and leading pharmaceutical, biotechnology, and medical device companies Leads the R&D compliance practice with a focus on clinical, preclinical, medical affairs, safety and quality systems for investigational products Prior to Quintiles: Vice President and Compliance Officer, Schering-Plough h Research Institute t Director, Global Pharmaceutical and Health Sciences practice at PricewaterhouseCoopers, LLP Management positions in regulatory affairs, clinical research, manufacturing, quality and sales at Bristol-Myers Squibb BS in Psychology/Biology from Fordham University and MS in Medical Biology from Long Island University 4

5 Kristie Lauterbach Director Medical Quality, Eli Lilly and Company Kristie Lauterbach has more than 15 years of experience in the pharmaceutical industry, most of the time serving in various Operations and Quality roles within parenteral manufacturing Eight years at Eli Lilly and Company Experienced in building Quality Systems supporting Vendor Management for suppliers of components and raw materials in manufacturing, and Third Party Organizations that perform clinical research BA in Biology and MBA from Olivet Nazarene University 5

6 Matthew Stoudemayer Sr. Clinical i l Compliance Specialist Novartis Pharmaceutical Corporation Matt Stoudemayer is responsible for Global GCP Auditing of Investigator Sites, Systems, and Third-party Vendors at Novartis. In addition, he addresses all clinical development compliance questions and issues for the Translational Sciences (Phase I) Department at the company. Prior to joining Novartis, Matt held positions of increasing authority in GCP auditing at Schering-Plough Corporation. Before moving into the pharmaceutical industry, Matt served roles as a Clinical Research Coordinator and a basic research scientist in the fields of Dermatology and Cosmetics. Matt has extensive experience with Health Authority Inspections conducted by the FDA, MHRA, EMA, Afssaps, Swedish MOH, and other agencies. MS in Quality Assurance/Regulatory Affairs from Temple University and a BS in Criminal Justice from The University of Scranton. 6

7 Clinical Development Situation Pharmaceutical, biotechnology and medical device companies are moving away from end-to-end ownership of the development cycle for their new products Firms may have five or more partners handling various aspects of product development and submission of marketing applications on their behalf The challenge is how to ensure that external service providers are compliant particularly since a sponsor company remains liable 7

8 Clinical Development Clinical Trial Process Model Strategic Development Plan Plan Final Protocol Approved Startt Site(s) Initiated Conduct Last Patient Last Visit Database Lock Closeout Report CSR to Regulatory Submission/ Publication 8

9 Clinical Development Clinical Trial Process Model Strategic Development Plan Plan Final Protocol Approved Startt Site(s) Initiated Conduct Last Patient Last Visit Database Lock Closeout Report CSR to Regulatory Submission/ Publication Sponsor Requests for Outsourced Services Clinical Monitoring Project Management Regulatory Services Data Management Biostatistics Pharmacovigilance il Medical Writing Medical Advisor 9

10 Clinical Development Clinical Trial Process Model Strategic Development Plan Plan Final Protocol Approved Startt Site(s) Initiated Conduct Last Patient Last Visit Database Lock Closeout Report CSR to Regulatory Submission/ Publication Sponsor Expectations from Service Providers Building a relationship is critical Demonstrate accountability and commitment Service Provider as study team Communication and proactivity Quality, quality, quality 10

11 Industry Perspective 11

12 Clinical Quality Assurance s Perspectives on Management of Clinical i l Development Partners Matthew Stoudemayer Sr. Clinical Compliance Specialist Novartis

13 GCP Auditing of Third Party Vendors Pre-approval Assessments On-going g Audits Post effectiveness Audits

14 Key Problem Areas Communication Roles and responsibilities Properly trained and qualified staff Clear and concise conflict/issue resolution plan

15 Health Authorities Views FDA Warning letters to J&J and Icon, Inc Joint Inspections with EMA and FDA Overall trends indicate that CROs are being held responsible as well as Sponsor companies

16 Ensuring Compliance The key step to having proper oversight of a Vendor is to establish a partnership which involves the following: Specific agreed to roles and responsibilities Open and free communication, continuous and on-going Established conflict resolution as well as escalation plan Clear and concise objectives Documentation ti

17 Third Party Management Kristie Lauterbach, Director Global Medical Quality Eli Lilly and Company

18 Third Party Management- Why it s Important t Sponsor s bear the ultimate accountability for work being outsourced (outsourcing does not mean it s not your problem when something goes wrong) Regulatory agencies have heightened their surveillance and enforcement on clinical trials 18 Eli Lilly & Co Company Confidential

19 Select and Approve Procedure: Process Flow 19 Eli Lilly & Co Company Confidential

20 TPO Categorization Categorization Governance Construct Quality Risk Assessment / Metrics / Scorecard Strategic Longevity of relationship anticipated (typically 5+ yrs) Contribute to multiple projects Choose to limit sourcing to a few partners for applicable capability Share technology, Intellectual Property Executive Steering Committee Required Joint Operations Committee Required TPO Sponsor Work Team Required Separate Quality Agreement Required Signed by Sr. Director of Global Medical Quality Quality Representation on Governance Third Party Governance Risk Assessment Quality On-time Delivery Compliance Financial Business relationship health/trends Critical TPO Sponsor Required Separate Quality Third Party Governance Provides unique or special technology/capability/service; Joint Operations Committee Agreement optional based Risk Assessment Optional off of risk Quality Shares technologies and know-how Work Team Required Signed by Director of On-time Delivery Only one or a few vendors exists with limited alternatives Global Medical Quality Compliance May be specific to few molecules or platforms but impact If no Quality Agreement, can be high quality agreement Financial language is in contract Leverage Longevity of relationship anticipated (typically 3+ yrs) Low to moderate impact to many molecule projects or business systems Opportunity to leverage for cost savings across functions TPO Sponsor Required Work Team Required Separate Quality Agreement optional based off of risk Signed by Director of Global Medical Quality If no Quality Agreement, quality agreement language is in contract Third Party Governance Risk Assessment Quality On-time Delivery Compliance Financial Transactional Low spend, readily available services/deliverables Low switching cost TPO Sponsor Responsibilities with the Deliverable Owner Work Team Required Not required Quality On-time Delivery Compliance Financial 20 Eli Lilly & Co Company Confidential

21 Implement and Monitor: Process Flow 21 Eli Lilly & Co Company Confidential

22 Design Oversight HIG H GH IGH Quality Agreement Quality Workplan (per indicated risk level) Global Medical Quality P4 /M2 or above approval Quality Agreement Quality Workplan (adjusted per risk level); including documented TPO Oversight Plan Global Medical Quality M4 approval K RIS RISK LOW LOW Quality Agreement, language in contract Quality Workplan (adjusted per risk level) Deliverable owner/es approval + + Joint + Work Team TPO Sponsor Operations Committee Separate Quality Agreement, Signed by M3 Global Medical Quality Quality Workplan (adjusted per risk level) Executive Steering Committee LOW HIGH Transactional Leverage Critical Strategic 22 Eli Lilly & Co Company Confidential TPM CATEGORIZATION

23 Execute Oversight HIG H GH IGH Sign Quality Agreement Approve Quality Workplan (per indicated risk level) Global Medical Quality P4 /M2 or above approval Sign Quality Agreement Approve Quality Workplan (adjusted per risk level); including documented TPO Oversight Plan Global Medical Quality M4 approval K RIS RISK LOW LOW Sign contract which includes quality language Sign Quality Agreement, Signed by M3 Global Medical Quality Approve Quality Workplan Approve Quality Workplan (adjusted per risk level) (adjusted per risk level) Deliverable owner/es approval + + Joint + Executive Work Team TPO Sponsor Operations Steering Committee Committee LOW HIGH Transactional Leverage Critical Strategic 23 Eli Lilly & Co Company Confidential TPM CATEGORIZATION

24 Monitor Oversight HIG H GH IGH Provide feedback to TPO Periodic review of metrics Identify corrective actions Escalate issues through NTM Communicate through work teams Provide feedback to TPO Periodic review of metrics Identify corrective actions Escalate issues through governance, NTM Communicate through work teams, JOC, ESC as appropriate K RIS RISK Provide feedback to TPO Periodic review of metrics Identify corrective actions Escalate issues through NTM Provide feedback to TPO Periodic review of metrics Identify corrective actions Escalate issues through governance, NTM LOW LOW + + Joint + Work Team TPO Sponsor Operations Committee Executive Steering Committee LOW HIGH Transactional Leverage Critical Strategic 24 Eli Lilly & Co Company Confidential TPM CATEGORIZATION

25 Terminate and Close-out: out: Process Flow 25 Eli Lilly & Co Company Confidential

26 Celebrate the Successes Consolidated our TPO list (multiple working lists into one) Categorized all TPO s used in Clinical Research Established governance for our strategic t and key critical TPO s. Formed a governing body that reviews all requests for new TPO s, new work or new location at existing TPO. If a TPO on the current list can do the work, then why do we need to add another one! 26 Eli Lilly & Co Company Confidential

27 Lessons Learned Implementation, Implementation, Implementation Have a well thought out implementation plan prior to going live. There needs to be endorsement and accountability from the top down on the use and adherence to the process and tools being rolled out. Simplify, Simplify, Simplify The process and the tools should be simple to use. If not you can be assured it will become a check the box exercise. Educate, Educate, Educate Clear definition of R and R s.what does this mean to me? How will I need to operate differently? Accountability, Accountability, Accountability Verify compliance to your process (don t just trust it s happening) Hold your TPO s and yourselves accountable to make sure clear expectations are defined prior to work starting. 27 Eli Lilly & Co Company Confidential

28 Regulatory Compliance Oversight 28

29 Regulatory Compliance Oversight Value Proposition for the Sponsor Efficient and effective compliance oversight and monitoring Protection of human subjects Improved data quality and integrity Enhanced reputation assurance Legal and regulatory risk mitigation Faster compliance response More efficient business processes Reduced time to market 29

30 Regulatory Compliance Oversight Model Approach Diagnostic to Continuous Improvement GOVERNANCE* Service Provider Diagnostic Remediation Accountability & Oversight Continuous Improvement Risk Assessment Priority Risk Identification Corrective Action Performance Management Compliance & Quality Management * Governance by Compliance Council 30

31 For Additional Information Visit: or Michael Swiatocha Practice Leader, R&D Compliance and Bioresearch Monitoring Consulting at Quintiles