1 / 13

Real Time under an IDE

Real Time under an IDE. – CDC’s PCR and ELISA Investigational Protocols. Real Time Under an IDE: CDC SARS Laboratory Response . Phase I : Agent Identification Phase II: Assay Development Phase III: Assay Deployment. CDC SARS Laboratory Response – Phase I : March 2003.

grant
Download Presentation

Real Time under an IDE

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Real Time under an IDE – CDC’s PCR and ELISA Investigational Protocols

  2. Real Time Under an IDE: CDC SARS Laboratory Response • Phase I : Agent Identification • Phase II: Assay Development • Phase III: Assay Deployment

  3. CDC SARS Laboratory Response – Phase I : March 2003 • March 14: Outbreak investigation organized • March 15-16-17 : Samples arrived from Toronto, Thailand • March 18-22: Virus isolated by cell culture, identified by EM and IFA assay • March 23-24: Virus verified by PCR and sequencing; prototype ELISA developed

  4. CDC SARS Laboratory Response – Phase II: April 2003 • April 3: Initiated discussions for development of real-time PCR assay to be deployed to LRN laboratories • April 3 – 8: Discussions with FDA regarding filing IDE for real-time PCR assay • April 7- 18: Additional PCR “signatures” selected and assay optimized • LRN “protocols” developed, written, approved internally

  5. CDC SARS Laboratory Response – Phase II: April 2003 • Synthesize primers and probes, optimize conditions, evaluate performance of assay • Large scale production primers and probes, dispense and label, QC for performance • Alert LRN members of reagents that will need to be purchased • April 21: Large scale production EIA antigen complete • April 28: FDA determines that ELISA assay is “low risk”; abbreviated IDE appropriate

  6. IDE Process – Real Time PCR • Published reports • Unpublished reports • Investigational Plan • Purpose • Protocol • Risk Analysis • Description of the Device • Monitoring Procedures • Manufacturing Information • Investigator Information • IRB Information • Labeling • Informed Consent Materials

  7. IRB Documentation for Real Time PCR Assay – April 30 • SARS Coronavirus PCR Assay Protocol • Attachment A - Published Reports • Attachment B - Health care providers information • Attachment C - Informed consent • Attachment D1 - Specimen Submission Form • Attachment D2 - Specimen Submission Form - Planned Amendments • Attachment E - Participant Information Sheet • Attachment F - Laboratory Response Network (LRN) Procedure Coversheet • Attachment F1 - F3 - Laboratory Response Network (LRN) “Protocols” • Attachment G - SARS Assay History • Attachment H - Primers and Probes Package Information • Attachment I - SARS Primers and Probes Labeling • Attachment J – Participating Labs Agreement • Attachment K – Interim Guidance for those patients with mild or asymptomatic infection • Attachment L – Fact Sheet for Clinicians

  8. IRB Documentation for ELISA Assay • SARS Coronavirus EIA Assay Protocol • Attachment A: Informed Consent form • Attachment B: Health Care Provider Instructions • Attachment C1 & 2: Laboratory Submission form and laboratory submission amendment form • Attachment D: Interim Guidance for Asymptomatic and Mildly Ill Patients • Attachment E: Fact Sheet for Clinicians • Attachment F: Participant Information Document • Attachment G: EIA Assay “Procedure”

  9. CDC SARS Laboratory Response – Phase III: May 2003 • April 30: Submit preliminary IDE application for PCR assay to FDA • May 2: FDA granted conditional approval of IDE for PCR assay • May 1: Submit PCR assay protocol and associated documentation to IRB • IRB responded that protocol written following FDA guidelines did not accurately reflect public health intent; protocol was re-written

  10. CDC SARS Laboratory Response – Phase III: May 2003 • May 14: EIA Protocol submitted for IRB approval • May 15: Real time PCR protocol IRB approved • May 19: EIA protocol IRB approved • May 20: Discrepancies between Web documents and IRB approved EIA and PCR documents • May 28 : Submitted amendments for EIA and PCR documents to IRB • May 29: IRB approved amendments • May 30: EIA and PCR documents posted on CDC, APHL, and LRN web sites

  11. CDC SARS Laboratory Response – Phase III: June 2003 • June 3: CSTE raises issues regarding instructions within Healthcare Provider letter • June 4 – 10: Feedback from CSTE members • June 16: Submitted amendments to IRB for EIA and PCR protocols • June 18: IRB approved amendments to Healthcare Provider letter

  12. Lessons Learned • Definitions: protocol (human subjects) and lab “procedures” • Language: CDC and FDA speak different languages – difficulties applying FDA regulations for manufacturers in a public health setting • Due to public health emergency, multiple authors were needed and versions of documents resulted in confusion and contradictions in written documents • CDC excels in developing assays rapidly for public health emergencies; not designed to be a manufacturing facility

  13. Lessons Learned • CDC IRB has no experience or perspective in reviewing device protocols in a public health response setting • Necessity to obtain IRB approval delays the rapid release of current information in an outbreak situation • Cooperation between CDC and FDA facilitated completion of this process

More Related