FDA, Center for Devices & Radiological Health: Microbiology Devices Panel Meeting. June 29 th, 2011 Summary: Carol D. Hamilton MD

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1 FDA, Center for Devices & Radiological Health: Microbiology Devices Panel Meeting June 29 th, 2011 Summary: Carol D. Hamilton MD

2 Disclaimer: I am not an FDA employee nor am I speaking in any official capacity for the FDA. Senior Scientist FHI, Professor of Medicine, Duke University Panel member No COI

3 Classes/Paths to FDA Regulatory Clearance or Approval: TB Examples Class I Existing staining methods, solid media, and automated systems and associated media Class II Drug susceptibility testing from cultured isolates Class III NAAT from respiratory specimens Indirect assays, e.g., IGRA

4 Classes/Paths to FDA Regulatory Clearance or Approval: TB Examples Class I General FDA controls (requirements) are adequate to assure safe, effective device (GMP, record keeping, etc) Class II General controls not enough must file a pre-market notification (510(k)) and can be subject to additional controls (requirements) Class III Must do everything required in a 510(k) submission plus

5 Classes/Paths to FDA Regulatory Clearance or Approval: TB Examples Class III Manufacturing site inspection Clinical trial site inspection (Monitoring inspection) Post-market oversight Class III >> expensive and time than II > I

6 Discussion from Interested Parties Bill Burman, MD, Denver Public Health gave clinician s point of view Ken Castro, MD, CDC DTBE, gave public health point of view Speakers from APHL, ASM, Cepheid, Panel included representative from industry, consumers, and patient rep

7 Meeting Objectives Discussions and general advice for FDA Non-binding, non-voting meeting Potential re-classification of required regulatory pathway for existing and future NAAT & IGRA tests

8 Questions Considered by Panel: #1 For NAAT that detect MTb directly from respiratory samples Discuss risks associated with false positive and false negative test results Minimum device performance standards Could specific special controls, i.e., FDA guidance, be written that would allow reclassification from III to II, but still assure quality

9 Questions Considered by Panel: #2 For NAAT that detect GENETIC MUTATIONS ASSOCIATED WITH ANTIBIOTIC RESISTANCE TO MTb directly from respiratory samples Discuss risks associated with false positive and false negative test results Discuss use in low-incidence settings such as US, appropriate clinical trial/samples to be used Minimum device performance standards Could specific special controls, i.e., FDA guidance, be written that would allow re-classification from III to II, but still assure quality

10 Questions Considered by Panel: #3 For tests like IGRAs Discuss risks associated with false positive and false negative test results Discuss appropriate clinical trial design appropriate to study IGRA, when no gold standard exists for LTBI Minimum device performance standards Could specific special controls, i.e., FDA guidance, be written that would allow reclassification from III to II, but still assure quality

11 Questions Considered by Panel: #1 For NAAT that detect MTb directly from respiratory samples Agreement that even our gold standard liquid culture is imperfect Need for rapid tests that can be performed outside of tertiary care, TB lab-support, which perform better than AFB Panel was comfortable with change to Class II reclassification for NAAT with appropriate controls /guidance, including labeling that NAAT is adjunctive to standard culture and DST Full agreement

12 Questions Considered by Panel: #2 For NAAT that detect GENETIC MUTATIONS ASSOCIATED WITH ANTIBIOTIC RESISTANCE TO MTb directly from respiratory samples More concern expressed about potential false positives, which would be problematic if used in a low-incidence US setting Comments (from viral lab specialists) that special controls should include post-marketing genotyping analysis of culturepositive, NAAT-negative specimens to ensure that there is no drift in antigen detection Would need to allow archived and/or spiked specimens in addition to fresh specimens and studies from high-incidence settings Must be accompanied by standard culture and DST Consensus but not unanimity to move to Class II

13 Questions Considered by Panel: #3 For tests like IGRAs Acknowledgement that TST is highly imperfect, but also experience with IGRAs now reveals they also not a panacea test characteristic and laboratory performance issues Lack of gold standard for LTBI complicates studies using populations used in previous IGRA studies probably good route need to define population well, and consistently Some disagreement about how much post-marketing work need to be done concern that too many burdensome requirements would stifle new (needed) tests Consensus, but no unanimity, to move to Class II

14 Conclusions FDA will now take the panel s recommendations under advisement If they decide to go ahead with re-classification, they can do this without re-convening another panel, or if still questions, could convene another panel Develop special controls/guidance would be next step Timing? Comments from FDA?