Amanda B. Parrish, PhD, RAC Director, Regulatory Affairs and Quality Erika Segear, PhD, RAC

1. Office of Regulatory Affairs and Quality Updates from the Office of Regulatory Affairs and Quality (ORAQ):Regulatory Review RequirementsChanges in ORAQ CostsSubmission Processes Amanda B. Parrish, PhD, RAC Director, Regulatory Affairs and Quality Erika Segear, PhD, RAC Associate Director, Regulatory Affairs

2. Office of Regulatory Affairs and Quality ORAQ Background • Regulatory Affairs Group Founded in 2007 • Initiated and supported through Duke CTSA funding • Free and optional resource for the Duke community • Duke faculty not required to utilize services in order to conduct research requiring FDA oversight • First few years included 4 FTEs • Office Growth and Expansion • Study teams worked to support staff by adding effort into grants—developed a model for dedicated support of FTE • Expansion to centralize GMP QA support under ORAQ in 2016 with migration into the School of Medicine • Merged with DCRI Regulatory Services in 2019 • Currently, 28 RA and GMP QA professional staff members

3. ORAQ Organizational Structure

4. Office of Regulatory Affairs and Quality ORAQ Mission • ORAQ offers regulatory and quality assurance support in all aspects of clinical research from preclinical requirements to first-in-human studies and beyond. • Our goal is to provide the Duke community with the tools, training, and support needed to navigate the complex regulatory pathways that accompany translational research. We aim to do this by providing support in the following areas: • Early Regulatory Strategy Development • Preclinical Testing and GMP Manufacturing • Regulatory Submissions and Maintenance • FDA Meetings and Inspections • Education and Training • Outreach and Collaboration

5. Office of Regulatory Affairs and Quality Regulatory Affairs Landscape • Current Numbers: • Over 140 active INDs and 6 active IDEs • Over 155 approved applications (ITPs, ODDs, DMFs) • Approved BLA (marketing application) • SOM Concerns: • About 1/3-2/3 of regulatory submissions do not have any review • Post-hoc errors have been found putting IND/IDE holders at risk or causing delays • Challenge for teams to keep up with changing regulatory landscape • SOM Goals: Improve quality of submissions, decrease regulatory risk, and thwart delays

6. Office of Regulatory Affairs and Quality New Institutional Review Requirements • Previous Model: • Use of ORAQ for regulatory support is optional. • Proposed Change: • All FDA regulatory submissions associated with a clinical trial (IND/IDE/ITP) will be required to go through ORAQ for review.

7. Office of Regulatory Affairs and Quality New Institutional Review Requirements • The initial application and/or amendment can still be drafted by the study team, but the submission needs to be reviewed by ORAQ before being sent to FDA. • The submission can be prepared and shipped by the study team, but ORAQ will offer support for this work to aid the study teams with this workload. • ORAQ must obtain a final copy of all submissions and will store in a central repository. • The study team can still serve as the secondary FDA contact, but any formal FDA correspondence (requests for information, etc.) should be shared with ORAQ.

8. Office of Regulatory Affairs and Quality New Institutional Review Requirements • Timeline: Requirements will be phased in with review of initial/original applications starting November 1, 2019. • Start collecting copies of all submissions at this time. • Obtain information on submission burden and evaluate ORAQ resources. • Review of additional submissions, such as supplements, reports, amendments, etc., will be phased in over a period of one year. We will notify sponsors and research support staff directly when new review requirements go into effect. Up to date information will also be available on our website.

9. Office of Regulatory Affairs and Quality New Institutional Review Requirements • What is the process for requesting reviews? • Workflows and review processes are in development. • In the next couple of weeks, we anticipate having a service request form available on our website. • Request review of initial/original submissions • Submit copies of all submissions • Website will also outline expectations on ORAQ review times and submission processes.

10. Office of Regulatory Affairs and Quality Changes in ORAQ Costs • Previous Model: • ORAQ services were no cost to the clinical research community at Duke University. • Proposed Change: • ORAQ will move to a cost recovery model, whereby effort that is not already paid for will be charged back to academic departments or fund codes monthly. • This change was communicated by SOM leadership to Department Chairs in an August 2019 meeting.

11. Office of Regulatory Affairs and Quality ORAQ Costs • ORAQ’s Service Request Form will contain fields for faculty and/or support staff to self-report department or fund code for charge back. • Collaborative projects will be required to select a primary department or fund code for billing. • This determination will be made by the study team or faculty involved in the project. • Study teams should work with ORAQ to estimate project costs and plan for these costs in grant applications.

12. Office of Regulatory Affairs and Quality New Submission Processes • Previous Model: • All drug/biologic submissions sent to CDER or CBER for research INDs (i.e., non-commercial INDs) submitted in triplicate on paper and shipped FedEx overnight. • Proposed Change: • All drug/biologic submissions sent to CDER or CBER for research INDs will be submitted electronically through FDA’s Electronic Submissions Gateway in non-eCTD format .

13. Office of Regulatory Affairs and Quality New Submission Processes • Advantages: • Faster receipt times—submission arrives same day • Less burdensome preparation • More cost effective • Non-eCTD submissions can be converted back to paper if faculty ever leave Duke • Important changes: ORAQ will provide study teams with an electronic copy (merged PDF) of the final submission for record keeping. Hard copies will no longer be provided.

14. Office of Regulatory Affairs and Quality Additional information

15. Office of Regulatory Affairs and Quality Additional information • Information on Website • Newsletter Messaging • Emails to Current Regulatory Sponsors • Emails to Research Support Offices • Research Wednesday Presentation (2/26/2020)

16. Office of Regulatory Affairs and Quality Additional information

17. Office of Regulatory Affairs and Quality ORAQ Resources • Location: Office of Regulatory Affairs and Quality Duke University – Hock Plaza 2424 Erwin Road, 4th Floor Durham, NC 27705 • Website: http://medschool.duke.edu/ORAQ • Includes new and updated regulatory template documents • Contact information for our staff • Event subscription/Request a Speaker • Additional QA resources • Training Program: ORAQ-TrainingProgram@duke.edu • Contact for Questions: ORAQ@duke.edu

18. Office of Regulatory Affairs and Quality Questions/Discussion