www.hhs.gov U.S. Department of Health and Human Services
Activity Outline
FDA Grand Rounds: Detection of transmissible spongiform encephalopathy agents in biological products using protein aggregation assays
February 13, 2020
WO 32: 1243
Activity Coordinators:
Devin Thomas (Devin.Thomas@fda.hhs.gov)
Series Description

The FDA Grand Rounds is webcast every other month to highlight cutting-edge research underway across the agency and its impact on protecting and advancing public health. Each session features an FDA scientist presenting on a key public health challenge and how FDA is applying science to its regulatory activities.

Lecture Description
Transmissible spongiform encephalopathies (TSEs or prion diseases) are rare fatal illnesses that have been transmitted by contaminated biologics such as tissues and blood products, surgical instruments and certain drugs (hormones) derived from human pituitary glands. We are interested in variant Creutzfeldt-Jakob disease (vCJD), a human TSE transmitted by blood transfusions and plasma products. Although vCJD is very rare, its impact is devastating because there is no vaccine and no cure. All TSEs have long asymptomatic incubation periods. During this phase the host appears healthy and can donate infected blood or tissues. In this presentation, we will describe our results detecting vCJD agent in blood of macaques experimentally infected with vCJD agent using an in vitro test called "protein misfolding cyclic amplification" (PMCA). The macaque blood panels are also offered to help assay developers to validate candidate blood screening tests. We will also describe another in vitro method called "real-time quaking-induced conversion" (RT-QuIC) that we used to detect TSE agent in biological materials other than blood.
This research has public health impact because new rapid tests for TSE diseases are needed to improve the safety of blood and tissue donations and to possibly screen those biologicals that are at risk of being contaminated with the TSE agent.
  • Will RG. Acquired prion disease: iatrogenic CJD, variant CJD, kuru. Br Med Bull. 2003;66: 255-265.
  • Morales R, Duran-Aniotz C, Diaz-Espinoza R, Camacho MV, Soto C. Protein misfolding cyclic amplification of infectious prions. Nat Protoc. 2012;7: 1397-1409.
  • OrrĂ¹ CD, Groveman BR, Hughson AG, Manca M, Raymond LD, Raymond GJ, Campbell KJ, Anson KJ, Kraus A, Caughey B. RT-QuIC assays for prion disease detection and diagnostics. Methods Mol Biol. 2017;1658: 185-203.
  • Kaelber N, Bett C, Asher DM, Gregori L. Quaking-induced conversion of prion protein on a thermal mixer accelerates detection in brains infected with transmissible spongiform encephalopathy agents. PLoS One. 2019 Dec 12;14(12):e0225904.
  • Bett C, Grgac K, Long D, Karfunkle M, Keire DA, Asher DM, Gregori L. A heparin purification process removes spiked transmissible spongiform encephalopathy agent. AAPS J. 2017; 19(3):765-771.
  • Gregori L, Serer A, McDowell KL, Cervenak J, Asher DM Rapid testing for Creutzfeldt-Jakob disease in donors of cornea. Transplantation. 2017; 101(4):e120-4.
Series Objectives
  • Discuss the research conducted at the FDA
  • Explain how FDA science impacts public health
Learning Objectives After completion of this activity, the participant will be able to:
  • Explain the basic principle of protein misfolding cyclic amplification assay
  • Explain the basic principle of real-time quaking-induced conversion assay
  • Describe and name various TSE diseases
Target Audience
This activity is intended for physicians, pharmacists, nurses, and other scientists within the agency external scientific communities.

Lecture 1 February 13, 2020
Time Topic Speaker
12:00 - 1:00 PM Detection of transmissible spongiform encephalopathy agents in biological products using protein aggregation assays Luisa Gregori
Continuing Education Accreditation
Jointly Accredited Provider
In support of improving patient care, FDA Center for Drug Evaluation and Research is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
ICPE Credit
This activity was planned by and for the healthcare team, and learners will receive 1 Interprofessional Continuing Education (IPCE) credit(s) for learning and change.
FDA Center for Drug Evaluation and Research designates this live activity for a maximum of 1.00 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity.
This knowledge-based activity has been assigned ACPE Universal Activity Number JA0002895-0000-20-022-L04-P for 1.00 contact hour(s).
FDA Center for Drug Evaluation and Research designates this activity for 1.00 contact hour(s).
Requirements for Receiving CE Credit

Physicians, pharmacists, nurses, and those claiming non-physician CME: participants must attest to their attendance and complete the final activity evaluation via the CE Portal (ceportal.fda.gov). For multi-day activities, participants must attest to their attendance and complete the faculty evaluation each day. Final activity evaluations must be completed within two weeks after the activity - no exceptions.

Pharmacists will need their NABP e-profile ID number as well as their DOB in MMDD format in order to claim CE credit.

Important Note regarding completion of evaluations and receiving credit
Attendees have 14 days from the last day of the activity to log in, complete the required evaluation(s) and attest to your attendance to claim credit.Physicians and nurses may then view/print statement of credit. Pharmacists should log into the CPE monitor 10 weeks after the last session of the activity to obtain their CE credit.

  • Gregori, Luisa, principal investigator, FDA/CBER - nothing to disclose

Planning Committee
  • Dinatale, Miriam, Team Leader, Food and Drug Administration - nothing to disclose
  • Pfundt, Tiffany, PharmD, Pharmacist, FDA - nothing to disclose
  • Thomas, Devin, LCDR, MPH, CHES, Health Promotions Specialist, FDA/OC/OCS/OSPD - nothing to disclose
  • Wheelock, Leslie, MS, RN, Director, OSPD, FDA, OC, OCS, OSPD - nothing to disclose

CE Consultation and Accreditation Team
  • Bryant, Traci, M.A.T., CE Consultant, FDA/CDER/OEP/DLOD - nothing to disclose
  • Zawalick, Karen, CE Team Leader, FDA/CDER/OEP/DLOD - nothing to disclose
Registration Fee and Refunds
Registration is complimentary, therefore refunds are not applicable.
ACCME Joint Accreditation
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