FDA Watch: Agency Finalizes CLIA Waiver Guidance for New IV Devices
On Feb. 25, the FDA issued a pair of final guidances to help manufacturers seeking clearance for new in vitro diagnostic devices. Here are the highlights. CLIA Waivers The first guidance document, “Recommendations for CLIA Waiver Applications for Manufacturers of In Vitro Diagnostic Devices,” explains how sponsors can demonstrate accuracy, i.e., “insignificant risk of erroneous result,” of in vitro diagnostic tests for purposes of obtaining a CLIA waiver. Among other things, it recommends that sponsors use a two-tier approach to demonstrate that their device is robust and has appropriate and effective risk control measures to ensure insignificant risk of an erroneous result: Tier 1: Risk Analysis and Flex Studies. Sponsors should conduct a systematic and comprehensive risk analysis identifying all potential sources of error, including test system failures and operator errors, and which of these errors can lead to a risk of a hazardous situation; and Tier 2: Fail-Safe and Failure Alert Mechanisms. Sponsors should also identify the control measures, including fail-safe and failure alert mechanisms that will reduce risks for each of the sources of error they identify. Then, once the control measures have been implemented, they should (1) verify that each control measure has been properly implemented, and (2) verify […]
On Feb. 25, the FDA issued a pair of final guidances to help manufacturers seeking clearance for new in vitro diagnostic devices. Here are the highlights.
CLIA Waivers
The first guidance document, “Recommendations for CLIA Waiver Applications for Manufacturers of In Vitro Diagnostic Devices,” explains how sponsors can demonstrate accuracy, i.e., “insignificant risk of erroneous result,” of in vitro diagnostic tests for purposes of obtaining a CLIA waiver. Among other things, it recommends that sponsors use a two-tier approach to demonstrate that their device is robust and has appropriate and effective risk control measures to ensure insignificant risk of an erroneous result:
- Tier 1: Risk Analysis and Flex Studies. Sponsors should conduct a systematic and comprehensive risk analysis identifying all potential sources of error, including test system failures and operator errors, and which of these errors can lead to a risk of a hazardous situation; and
- Tier 2: Fail-Safe and Failure Alert Mechanisms. Sponsors should also identify the control measures, including fail-safe and failure alert mechanisms that will reduce risks for each of the sources of error they identify. Then, once the control measures have been implemented, they should (1) verify that each control measure has been properly implemented, and (2) verify and/or validate the effectiveness of each control measure.
Dual 510(k) and CLIA Waiver Submissions
The second guidance document, “Recommendations for Dual 510(k) and CLIA Waiver by Application Studies,” aims to make the dual CLIA waiver and Section 510(k) clearance pathway for certain Class I and Class II IVD devices created as part of the Medical Device Use Fee Amendment of 2012 less burdensome. For dual submission, the guidance recommends that sponsors include:
- A device description;
- A determination that a device is simple to use;
- Results of a risk analysis with potential sources of error identified;
- Failure-alert and fail-safe mechanisms that have been verified to mitigate risk of errors;
- Flex studies demonstrating insensitivity of the test to environmental and usage variations under stress conditions;
- Descriptions of the design;
- Results of analytical studies testing sensitivity, measuring interval, specificity, linearity, precision, carry-over, reagent stability and sample stability;
- Comparison studies and reproducibility studies;
- Clinical performance studies, if necessary; and
- Proposed device labeling.
New FDA Approvals
Key new product approvals announced from late-January through late February 2020:
NEW FDA APPROVALS
| Manufacturer(s) | Product(s) |
| US Centers for Disease Control and Prevention | Emergency Use Authorization for 2019-nCoV Real-Time RT-PCR Diagnostic Panel to detect coronavirus |
| Asuragen | Clearance to market AmplideX Fragile X Dx and Carrier Screen Kit, first genetic test for fragile X syndrome (FXS). |
| Lucid Diagnostics | Breakthrough device designation for EsoGuard Esophageal DNA Test to detect esophageal dysplasia and potential cancer risk run on EsoCheck Cell Collection Device |
| Siemens Healthineers | 510(k) clearance for Advia Centaur Total IgE assay to detect total IgE in serum + plasma run on Advia Centaur, Advia Centaur XP + Advia Centaur XPT systems |
| DiaSorin | Clearance for Liaison Lyme Total Antibody Plus assay and Liaison Lyme Total Antibody Plus Control Set to detect lgG and IgM antibodies to Borrelia burgdorferi in serum and plasma samples |
| Thermo Fisher Scientific | Clearance for Sensititre 20- to 24-hour Haemophilus influenzae/Streptococcus pneumoniae minimum inhibitory concentration or breakpoint susceptibility system with lefamulin (Nabriva’s Xenleta), in 0.008 to 16 µg/mL dilution range |
| Shenzhen Bioeasy Biotechnology | Clearance for Bioeasy Multi-Drug Test Cup assays to detect drugs in human urine at specified cutoff concentrations |
| Beckman Coulter | 510(k) clearance for Access PCT assay |
New CE Marks & Global Certifications
Notable European CE certifications announced during the period:
NEW CE MARKINGS IN EUROPE
| Manufacturer(s) | Product(s) |
| Primerdesign (division of Novacyt) | CE marking for molecular test to detect COVID-19 virus |
| Quotient Limited | CE marking for serological disease screening (SDS) microarray run on firm’s Mosaiq system for blood grouping and transfusion-transmitted infection screening |
| Bioneer | CE-IVD marking for AccuPower hepatitis B virus quantitative PCR kit |
| DrawBridge Health | CE marking for OneDraw test system for collecting blood samples from upper arm for hemoglobin A1C testing without a needle |
| Qiagen | CE marking for Therascreen PIK3CA RGQ PCR kit for identifying breast cancer patients with PIK3CA mutation |
| NeuMoDx Molecular | CE-IVD marking for assay to detect and differentiate Trichomonas vaginalis and/or Mycoplasma genitalium in urine samples |
Other international clearances announced during the period:
| Manufacturer(s) | Country(ies) | Product(s) |
| BGI + MGI Tech subsidiary |
China | National Medical Products Administration (NMPA) emergency use approval for: * metagenomic sequencing kit for coronaviruses *2019 novel coronavirus reverse transcription PCR kit *ultra-high-throughput sequencer DNBSEQ-T7 |
| Genetron Health | China | NMPA emergency use approval for Genetron S2000 NGS system + a kit for an eight-gene lung cancer panel |
| Seegene | Korea | Ministry of Food and Drug Safety emergency use approval for Allplex 2019-nCoV coronavirus detection assay |
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