Regulatory Considerations for Investigational Assays: Planning for Success

1. Regulatory Considerations for Investigational Assays:Planning for Success Elizabeth Mansfield, PhD OIVD/FDA “Next-Generation DNA Sequencing as a Tool for Clinical Decision-making in Cancer Patient Management” May 3-4, 2012

2. Overview • What defines an investigational assay? • How are levels of risk assessed? • What types of information and data are needed? • How do I submit this information to FDA (if required)?

3. Investigational Use • Per 21 CFR 812, an investigation means “a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device” • Applies when device is being studied for • Its own safety and effectiveness • Its safety and effectiveness in the context of other investigational products

4. What is FDA’s Interest in Investigations? • SAFETY of / risk to the patient when exposed to investigational use of a device (performance and use) • Appropriate oversight of investigation (IRB) • Adequate informed consent for subjects • Compliance of investigators

5. Investigational Assays • An assay is considered to be used in an investigational manner when: • It has not been cleared or approved for the use to which it is being put • This encompasses LDTs, which have generally not been cleared or approved for any use • The investigational use is applied to subjects (humans, whether whole or in parts)

6. Assessing Level of Risk for IVDs: Exempt • No risk of harm to patient • Results not used for clinical management • Generally not returned to physician/patient • If returned, must be confirmed by another accepted (approved or cleared) procedure • No invasive procedures related to test required that might harm the patient • Doesn’t include sample collection for other medically necessary reasons • Doesn’t include venipuncture

7. Assessing Level of Risk for IVDs: Significant Risk • Presents a potential for serious risk to the health, safety, or welfare of the patient • Invasive sampling solely for use in testing • Results returned for patient management without confirmation by another procedure • Management of patient according to results could result in harm • Esp. when test results are incorrect

8. Assessing Level of Risk for IVDs: Non-significant Risk • Doesn’t meet requirements to be exempt, but does not present a potential for serious risk to patient • No significant risk invasive sampling needed • If results are returned, unlikely to harm patient even if result is incorrect

9. What Should Sponsor Do? • Familiarity with Part 812 • Submit study to IRB for assessment • Prepare informed consent • Prepare a detailed protocol for how the test will be used • Obtain good investigator agreements • Submit IDE/IND to FDA if needed

10. IDE: What Does FDA Want? • 21 CFR Parts 50 and 56 apply • Exempt investigations: No submission to FDA, but FDA may disqualify an investigator. • Non-significant risk investigations: abbreviated requirements, no submission to FDA • Significant risk investigations: IDE submission required

11. IDE Review • Subjects’ safety • Knowledge to be gained from investigation • Alignment with plans for later development and FDA review • Usually includes analytical validation data

12. Device “ready” for use to guide accrual, treatment, or asses outcome in a clinical trial? • Fully specified device, for purposes of the trial • Analytical performance adequately assessed • Pre-clinical or clinical information justifies subjects’ “exposure” • Well-posed question or hypothesis can be answered/tested by the trial

13. Submitting an Investigational Application • IDE: Submission to CDRH, identified as an IDE application • 30-day review clock • Decision: • Approved • Approved with modifications • Disapproved • Can resubmit with new info if disapproved • If part of non-exempt IND, can be submitted to IND • If part of an exempt IND, must submit IDE

14. Thanks! • Elizabeth.mansfield@fda.hhs.gov