Strategic Approaches to Outsourcing to Clinical Research Organizations

1. Strategic Approaches to Outsourcing to Clinical Research Organizations Kate Giovino Director of Clinical Operations

2. Experience Class III Medical Devices • Living bi-layered skin substitute • Spinal implants • Bone morphogenetic protein There is tremendous diversity in Medical Devices

3. Establishing SOPs Hiring employees with experience in conducting clinical studies Utilizing a consultant such as a CRO for study functions beyond the sponsor's in-house capabilities Conducting internal and external audits of the clinical study processes, procedures and personnel Review of clinical study issues by management with executive responsibilities Strategic use of CROs can directly contribute to the effectiveness of device sponsors, as assessed by these 5 habits. 5 Habits of Highly Effective Device Sponsors

4. Objectives • Utilizing a consultant such as a CRO for study functions beyond the sponsor's in-house capabilities • What can potentially be outsourced in the conduct of clinical trials • How to decide for your organization • Lessons learned - sometimes the hard way!

5. General Questions to Ask • What are the capabilities and capacity of existing clinical personnel? • What are the critical business factors (e.g., time, money, headcount) for the organization? • What are the long-term needs to support clinical development? • Do they substantiate in-house capabilities?

6. What to Outsource? • SOP development • Protocol development • Monitoring / Project Management • Data Management / Statistics • Audits of internal and external of clinical processes, procedures and personnel

7. SOP development • Dependent on other outsourcing decisions • Highly outsourced  need for simple SOPs • Key processes internal  need for detailed SOPs • Lessons learned • Too busy to write SOPs • Contracted out • Non-specific and unusable (poor vendor selection) CenterWatch: Standard Operating Procedures for Good Clinical Practice by Sponsors of Medical Device Trials ($6000) Expertise of vendor was clinical drug development, not medical devices

8. Protocol Development • A well-written and unambiguous protocol is one of the key factors in the success of a clinical study Consultation with a Lead Investigator(s) Clinical operations point of view HOW WELL DOES YOUR ORGANIZATION ATTEND TO THIS BALANCE?

9. Monitoring and Project Management

10. Monitoring and Project Management Experiences • Things that don’t work… • Trying to manage ex-US clinical sites/studies without in-country clinical expertise. • Not having in-house experienced clinical research personnel to closely oversee any contracted CROs. • Not having executive management who recognize and value the complexities of clinical research and are committed to fulfilling their management responsibilities.

11. Data Management • What are the short-term and long-term needs? • When does it become cost-efficient to bring a data management system in-house • Paper-based or electronic data capture? • What types of clinical studies are you conducting? • Post-marketing • Pilot studies • Pivotal studies • What would be the key advantages/disadvantages of either in-house vs. outsourced data management

12. Data Management – IDE Experience

13. Data Management & Statistics • There is GREAT value in having an internal person(s) on your team who can speak APPLES TO APPLES regarding data management and statistical issues. • Strongly consider this a CORE competency to develop internally or with a strongly aligned consultant.

14. Internal and External Clinical Audits • Internal GCP audit • External audits • Key vendors (e.g., data management, core labs) • Clinical Sites WHAT & WHO ARE THE RESOURCES IN YOUR INTERNAL QUALITY ASSURANCE GROUP ?

15. Internal vs. External Auditors • Internal Auditors • Knowledgeable on device and general SOPs • Level of GCP expertise? • Co-audit QA & Clinical personnel • Minimal cost • External Auditors • High level of GCP expertise • High degree of independence from Sponsor • Additional cost

16. Internal GCP Audits • Assessment of training files • SOP review with gap analysis • In anticipation of a Sponsor audit by FDA

17. External Audits - CROs • Prior to CRO selection (optimal) • Assessing qualifications of key personnel • Assessing SOPs: comparability with internal SOPs and change control processes • Reviewing systems and processes for contracted services • Audits at other times • Routine, on-going basis • Prior to interim and/or final analysis • For cause….

18. Mock Audits Prior to Final Database Lock Why Now? Last opportunity to take a systematic look at the quality of the data How? Quality Assurance department or CRO Allow enough time to respond to the findings of the audits Which Sites? High enrolling sites, compliance concerns, or extremely high or low incidence of AEs External Audits – Clinical Sites

19. Establishing SOPs Hiring employees with experience in conducting clinical studies Utilizing a consultant such as a CRO for study functions beyond the sponsor's in-house capabilities Conducting internal and external audits of the clinical study processes, procedures and personnel Review of clinical study issues by management with executive responsibilities YES  with customization to your organization Need core expertise in your organization to oversee and manage CROs YES  with careful selection of CRO and thoughtful decisions regarding which functions to outsource YES  especially when internal QA resources are limited or GMP/GLP focused NO  Must be a retained responsibility within your organization 5 Habits of Highly Effective Device Sponsors – CRO involvement

20. CONCLUSIONS • Decide on an approach that meets the needs of your organization considering the following: • Competencies and capacity of in-house clinical personnel • Key business needs • Carefully select your CRO to match the needs of your organization • Alignment with values, priorities and needs

21. Further questions: Kate Giovino kgiovino@organo.com 781-401-1136