FDA Update

Peter Tobin, Ph.D.Division of Program Operations and ManagementOffice of In Vitro Diagnostics and Radiological HealthCenter for Devices and Radiological HealthU.S. Food and Drug Administration

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Outline:

• CDRH Reorganization and Staffing Changes

• Precision Medicine Updates

• Biotin Safety Communication

• SHIELD Updates

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CDRH has reorganized to support a Total Product Life Cycle (TPLC) approach

CDRH

Office of Communication and EducationOffice of the Director

Office of Device EvaluationOffice of Compliance

Office of ManagementOffice of In Vitro Diagnostics and Radiological Health

Office of Surveillance and Biometrics

Office of Science and Engineering Laboratories

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Office of Product Evaluation and Quality (OPEQ)

OHT Scope of Products / Responsibilities Office Director

OHT 1 Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices

Malvina Eydelman, M.D.

OHT 2 Cardiovascular Devices Bram Zuckerman, M.D.

OHT 3 Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors

Ben Fisher, Ph.D.

OHT 4 Surgical and Infection Control Devices Binita Ashar, M.D.

OHT 5 Neurological and Physical Medicine Devices Carlos Pena, Ph.D.

OHT 6 Orthopedic Devices Raquel Peat, Ph.D., MPH

OHT 7 /OIR

In Vitro Diagnostics and Radiological Health Tim Stenzel, MD, PhD

ORP Programmatic oversight for premarket, postmarketand compliance activities

CAPT Sean Boyd

OCEA Programmatic oversight for clinical trial, BIMO, RWE, and statistical activities

Daniel Caños, PhD, MPH (Acting)

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Office of In Vitro Diagnostics and Radiological Health (OIR)

Division of Chemistry and Toxicology Devices

(DCTD)

Director – Kellie Kelm (Acting)Deputy – Marianela Perez-Torres

(Acting)

Division of Immunology and Hematology Devices

(DIHD)

Director – Lea CarringtonDeputy – Takeesha Taylor-Bell

(Acting)

Division of Microbiology Devices (DMD)

Director – Uwe ScherfDeputy – Steve Gitterman

Division of Program Operations and Management (DPOM)

Director – Brendan O’LearyDeputy – Robert Sauer

Division of Molecular Genetics and Pathology (DMGP)

Director – Reena PhilipDeputy – Yun-Fu Hu

Division of Radiological Health (DRH)

Director – Thalia Mills Deputy – Michael O’HaraDeputy – LCDR David Dar

(Acting)

Division of Mammography Quality Standards (DMQS)

Director – David LeeDeputy – Preetham Sudhaker

DirectorDeputy Dir. for New Product Evaluation

Deputy Dir. for Patient Safety and Product QualityDeputy Dir. for Personalized Medicine

Deputy Dir. for Radiological HealthAssociate Dir. for Programs and Performance

Associate Dir. for Strategic InitiativesAssociate Dir. for Regulatory Counsel

Associate Dir. for Medical AffairsChief Medical Officer for Radiological Health

Timothy StenzelDonald St. PierreCourtney Lias (Acting)Wendy RubinsteinRobert OchsToby Lowe (Acting)VacantScott McFarlandSara BrennerDonald L. Miller

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Introducing our new OIR/OHT7 Deputy and Associate Directors

Dr. Wendy Rubinstein, MD, PhD

Deputy Director for Personalized Medicine

Dr. Sara Brenner, MD, MPH

Associate Directorfor Medical Affairs

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FDA’s history of enabling precision medicine

• 37 unique companion diagnostics cleared or approved*

• More than 100 approved/cleared human nucleic acid based tests**

• More than 24 guidances issued since 2005

*https://www.fda.gov/medical-devices/vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-vitro-and-imaging-tools **https://www.fda.gov/medical-devices/vitro-diagnostics/nucleic-acid-based-tests

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FDA’s vision for regulation of NGS-based IVDs Technical/analytical standards for NGS for suspected

germline diseases The potential for an expedited path to market for test developers

that meet these standards. Standards would be developed with the scientific community, and

can be updated as science and technology advance.

Use of FDA-recognized databases to provide clinical evidence Use databases as information sources to support the link between

genetic variation and health/disease. Test developers may be able to use such databases in support or in

lieu of traditional clinical studies.

Develop, characterize, make publicly available NGS reference sample sets that can be used to support validation of NGS platforms. Make available characterized samples and sequence Generate evolving “truth” sequence.

https://www.fda.gov/medical-devices/vitro-diagnostics/precision-medicine

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ClinGen Recognition – Dec. 4, 2018

• FDA recognized as a source of valid scientific evidence that can be used to support clinical validity in premarket submissions

• Scope of recognition: germline variants for hereditary disease where there is a high likelihood that the disease or condition will materialize given a deleterious variant (i.e., high penetrance).

• For more info, see the Decision Summary

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Draft guidance describes when bioinformatics software is a medical device

• “Software products that provide patient specific information based on “omics” data often drive diagnostic and treatment decisions. These software products are device functions, because they are intended to aid in treatment of a disease or condition and because they process a signal from an IVD.”

• “Bioinformatics software products that query multiple genetic variants against reference databases or other information sources to make patient-specific recommendations about the significance of a patient’s variants are devices”

Read the draft guidance for full context and please comment

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Updated Safety Communication:FDA Warns that Biotin May Interfere with Lab Tests

• On November 5, 2019, FDA updated our 2017 safety communication

• Biotin, often found in dietary supplements, can significantly interfere with certain lab tests and cause incorrect results that may go undetected

• Some lab test developers have been successful at mitigating the biotin interference of their assays, but others have not yet addressed it

• FDA has continued to receive adverse events reports indicating biotin interference caused falsely low troponin results

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New FDA Webpage:Biotin Interference with Troponin Lab Tests –Assays Subject to Biotin Interference

• FDA remains concerned about troponin laboratory tests that have not addressed the risk of biotin interference

• Webpage includes list of FDA listed troponin IVDsthat are subject to biotin interference but have not addressed this risk

• FDA wants to make the public and health care providers aware about biotin interference with lab tests so that patients, physicians, and laboratories can work together to help prevent adverse events

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SHIELD implementation pilots of lab data standards to be completed in 9 labs by Sept 2021

Pre-Process & Automation

Laboratory

Standardized

IVDIndustry

LIS/ LIMS

Test Catalog

AutoVendor 2 Analyzer 2Standard

StandardVendor 1 AutoAnalyzer 1

AutoVendor 3 Analyzer 3Standard

Auto… …Standard

Providers

Orders

Results

Registries CDC OtherLabs

Interested in participating?Implementation pilot opportunities are still available

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CLSI and SHIELD are developing a harmonized way to navigate lab data standards

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Function of data standards for lab implementationStandard Function Curating Organization LinkLOINC

(Logical Observations Identifiers Names and Codes)

Semantic Standards

A semantic standard that describes the question an IVD asks of a specimen. There are over 55,000 LOINC codes describing each type of IVD test.

Regenstrief Institute https://loinc.org/get-started/what-loinc-is/

SNOMED-CT

(Systematized Nomenclature of Medicine – Clinical Terms)

A semantic standard used here to describe the results of qualitative tests, e.g., detected, not detected, drug-resistant, etc.

International Health Terminology Standards Development Organization (IHTSDO)

https://www.snomed.org/snomed-ct

UCUM

(Unified Codes for Units of Measure)

A semantic standard assisting in the application of scientific units to the results of quantitative tests.

Regenstrief Institute http://www.unitsofmeasure.org/trac

UDI

(Unique Device Identification System)

A standard identification system for each specific IVD. Food and Drug Administration (FDA) https://www.fda.gov/medicaldevices/deviceregulationandguidance/uniquedeviceidentification/udibasics/default.htm

LOINC Manuals Transmission/ Mapping

A standardized way for all IVD manufacturers and labs to ensure the same appropriate LOINC code is assigned to the same type of device.

Regenstrief Institute https://loinc.org/guides/micro/

LIVD

(Digital Format for Publication of LOINC to Vendor IVD Test Results)

A standard structured format for all IVD manufacturers to send the descriptive codes (listed above) to laboratory for the tests they provide, helping ensure that labs are presented with information in the same format regardless of the manufacturer.

IVD Industry Connectivity Consortium (IICC)

https://ivdconnectivity.org/livd/

LAW

(Laboratory Analytical Workflow)

A standard enabling plug-and-play ability for an instrument to send IVD descriptive information directly into an LIS.

Clinical Laboratory Standards Institute (CLSI)

https://wiki.ihe.net/index.php/Laboratory_Analytical_Workflow_Profile

LIVD FHIR Profile

(Fast Healthcare Interchange Resources)

A standardized way to map LIVD content provided by IVD manufacturers into electronic healthcare record

Health-Level 7 (HL7) http://hl7.org/fhir/uv/livd/2018Sep/index.html

SOLOR

(SNOMED , LOINC, RxNorm)

A standard to help ensure version control and appropriate association between LOINC, SNOMED-CT, and RxNorm(prescriptions)

Veterans Health Administration (VHA)

http://solor.io/

CIMI

(Clinical Information Modeling Initiative)

A shared repository to harmonize different clinical models so information can ultimately be presented consistently in front of a clinician.

Healthcare Services Platform Consortium (HSPC)

https://www.hl7.org/Special/Committees/cimi/overview.cfm

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Questions?

CLIA@fda.hhs.gov