Testing Commons: 2021 Year in Review

TestingCommons.com

COVID Diagnostics:

The Beginning, Middle and End of the Pandemic 2022: The Year of The Test

TestingCommons.com A one-stop reliable source for comprehensive information about COVID-19 tests worldwide. Search all tests in the market and in the pipeline by multiple parameters including test type, technology, regulatory status, country of origin and more.

TestingCommons.com, part of COVID Diagnostics Commons initiative, at Arizona State University’s College of Health Solutions Testing Commons is made possible with support from The Rockefeller Foundation 2

TestingCommons.com 2021 Summary • Total EUA activity • 133 EUA’s in 2021 vs. 188 EUA’s in 2020 Schedule IV

EUA

EUA

• Antigen Rapid Self-Test EUA activity • 2021 Q1 through Q3 – 6 new EUA’s • 2021 Q4 – 6 new EUA’s (ACON, Celltrion, InBios, iHealth, SD BioSensor (Roche), Siemens)

• Molecular EUA activity • 2021 3 Rapid Molecular [Cue in Q1, Lucira in Q2, Detect in Q4] • 2021 Lab Based Molecular – 43 new EUAs [for COVID assays, excludes multi-analyte panels and collection kits] Questions: mara.aspinall@asu.edu

TestingCommons.com Pandemic Review

Molecular, Antigen, Serology, & T-Cell Tests, Patient Management, Combination Respiratory Panels and Collection Kits

FDA EUA LDT

Schedule IV

EUA EUA

Schedule IV notifications & Umbrella Molecular EUAs1 EU self-certification

CE-IVD Research Use Only

In US: not for clinical use. Outside US: commercially available Tests & Technologies publicly announced to be under development

Development FDA Revoked

Revoked, Rejected, Withdrawn, Warning letter, Fraud (DOJ) 0

200

400

600

1. Discontinued after 10/7/20 when HHS/FDA announced policy to not require authorization for COVID LDT

800

1000

1200

Questions: mara.aspinall@asu.edu

Pandemic Total through 12/31/21

US FDA EUA Test Classifications • Tests: • • • •

Molecular Tests (including Appendix A LDTs and Flu panels) Antigen Tests (including Flu panels) Patient Management Tests (IL6) Serology (Antibody) Tests (including cellular immunity)

• Collection Kits

• Home Collection Kits (Nasal Swabs or Saliva)

• Test Attributes: • • • • •

Test Location (Lab vs. POC vs. Home) Screening (Asymptomatic) Serial Screening Pooling OTC vs Prescription

US FDA Emergency Use Authorizations

250

Molecular

Number of Tests

200

150

Antibody

100

Other

Antigen

50

0

Molecular 88% RTqPCR 9% Isothermal 2% Sequencing 1% CRISPR

Antigen 92% Lateral Flow 8% other

Antibody 62% ELISA 35% Lateral Flow 3% Other

Other Collection Kits Flu/RSV Panels Patient Management

Pandemic Total through 12/31/21

Profile of US FDA EUA’s Lab Authorized to Analyze Sample

300

# Tests

250 200

CLIA High Complexity Lab

150 100 50

CLIA Moderate Complexity Lab

CLIA Waived / Point of Care Lab

Self Test (No Lab Required)

0 350 300

Swab

Sample Type

Collected1

300 250

# Tests

# Tests

250 200 150 100 50 0

Person to Collect Sample2

Saliva

Venous Blood

Fingerstick Blood

200 150 100 50 0

Health care or Trained Tech

Self Collect

Pandemic Total through 12/31/21

1. Only a single Swab type per test counted here, in least to most invasive priority order: Saliva; ANS; lastly NPS/OPS. All PCR tests are sensitive enough to work with nearly all of these swab types: later authorizations specify ANS in addition to other swab methods. 2. No specific Healthcare Professional training is required by the EUA (at Laboratory discretion)

16 EUA’s for OTC Self Tests MOLECULAR TESTS (3)

OTC TESTS (16)

• • • Cue for Home & OTC: • SINGLE • • • • Detect At-Home: SINGLE Sympt + • Serial Asymptomatic • • • Lucira CHECK-IT Test: • SINGLE • • • New Q4*

ANTIGEN TESTS (13)

Abbott BinaxNOW Card 2 Home: Serial: Asympt. & Single: Sympto Abbott BinaxNOW Ag Self: Serial: Asympt. & Single: Sympto Access Bio CareStart Home: Serial: Asympt. & Single: Sympto ACON Flowflex: Single for both: Asymptomatic and Sympto BD Veritor At-Home: Serial: Asympt. & Single: Sympto Celltrion At Home: Serial: Asympt. & Single: Sympto Ellume COVID-19 Home: Single for both: Asymptomatic and Sympto iHealth COVID-19 Home: Serial: Asympt. & Single: Sympto InBios Int’l Detect Self: Serial: Asympt. & Single: Sympto OraSure InteliSwab Rapid: Serial: Asympt. & Single: Sympto Quidel QuickVue At-Home: Serial: Asympt. & Single: Sympto Roche / SDBiosensor At-Home: Serial: Asympt. & Single: Sympto Siemens CLINITEST: Serial: Asympt. & Single: Sympto Pandemic Total through 12/31/21

43 Antigen Tests with EUAs CLIA High/Moderate (Lab)

Instrument read

Celltrion Sampinute DiaSorin LIAISON Ortho VITROS Qorvo Omnia QIAGEN QIAreach Quanterix Simoa

Visual read

New Q4*

CLIA Waived. (MD Office)

Home

BD Veritor BD Veritor + Flu A/B Ellume Luminostics Clip LumiraDx Quidel Sofia FIA Quidel Sofia2+Flu

BD Veritor Ellume OTC

Access Bio CareStart ANP Technologies NIDS BinaxNOW Card BinaxNOW 2 Card Celltrion DiaTrust GenBody COVID-19 Ag InBios SCoV-2 Nano-Ditech Nano-Check* OraSure Inteliswab Pro PHASE Scientific INDICAID Princeton Status+Flu Salofa Sienna-Clarity Quidel QuickVue Xtrava Health SPERA*

Access Bio CareStart ACON Flowflex* BinaxNOW Home Rx BinaxNOW Self OTC BinaxNOW Telehealth Celltrion DiaTrust* iHealth Rapid OTC* InBios CoV-2 Self* OraSure Inteliswab RX OraSure Inteliswab OTC Quidel QuickVue Rx Quidel QuickVue OTC Roche/SD Biosensor* Siemens CLINITEST*

Pandemic Total through 12/31/21

24 EUA’s for Respiratory Panels (Flu, RSV, etc.)

25

Number of Tests

20

15

10

5

0

Molecular (18) 80% Lab 20% POC

Antigen (3) 100% POC

Collection Kit (1) 100% Molecular Pandemic Total through 12/31/21

CE-IVD Certified Tests (Mostly Europe) Antigen

450

Antibody

400

Number of Tests

350 300

Molecular

250 200 150

Other

100 50 0

Molecular 91% RTqPCR 6% Isothermal 3% Other

Antigen 62% Lateral Flow 5% ELISA 33% Other

Antibody 37% Lateral Flow 46% ELISA 17 % Other

Other Collection Kits Flu/RSV Panels Pandemic Total through 12/31/21

Tests in Development Worldwide 120

Molecular

Number of Tests

100

Antigen

80

Antibody

60 40

Other

20 0

Molecular 40% RTqPCR 24% Isothermal 15% CRISPR 13% Sequencing 9% Other

Antigen 59% Lateral Flow 19% ELISA 9% Breath 13% Other

Antibody 61% Lateral Flow 30% ELISA 9% Other

Other Breath / VOC Mass Spec Raman Spec Pandemic Total through 12/31/21

Companies with the largest number of EUAs 12

12 11

10

Number of Tests

Pandemic Total through 12/31/21

10

8

8

8 7

6

6

6 5

4

5

5

Diasorin

Access Bio

2 0

Abbott

Siemens

Roche

Danaher*

Quidel

Thermo BD Quest Color Health Fisher 4 Molecular 1 Molecular 7 Molecular 4 Molecular 3 Molecular 6 Molecular 2 Molecular 5 Molecular 5 Molecular 1 Antigen 3 Antibody 5 Antigen 5 Antigen 1 Antigen 1 Antibody 3 Antigen 1 Collection 3 Antibody 8 Antibody 2 Antibody 1 Pt Mgmt 1 Pt Mgmt Kit 1 Pt Mgmt *Cepheid + Beckman Coulter

1 Molecular 1 Molecular 1 Antigen 2 Antigen 13 3 Antibody 2 Antibody

FDA Revoked EUA’s & Other Safety Communications Letters to Healthcare Providers (15) Safety Communications (9)

•

Safety Communications: FDA posts Medical Device Safety Communications to describe FDA’s analysis of a current issue and provide specific regulatory approaches and clinical recommendations for patient management.

•

Letters to Healthcare Providers: FDA posts the letters it sends to health care providers about safety concerns with medical devices used in health care facilities.

Revoked Antigen EUA (5) Revoked Molecular EUA (15)

Revoked Antibody EUA (171)

Pandemic Total through 12/31/21

Other FDA Safety Communications by Subject

Warning Letters to Ancillary Companies - Blue Willow Biologics - Invisi Smart Technologies - Jordan’s Crossing Herbal Connections - Kaleido Biosciences, Inc. - Mahita, LLC dba PushMyCart - Rxmedcart.com - Shanghai Dasheng

Letters to Health Care Providers - BD Max - ThermoFisher - Roche

Safety Communications - Abbott - Curative - Ellume - Innova - Leccurate - Lepu Medical - Quidel

Letters to Health Care Providers - Antibody Testing (2) - Transport Media - Self Testing / Nasal Swabs - Rapid Antigen Tests - Variants

Safety Communications - Antibody Testing - Veterinary Ivermectin

Pandemic Total through 12/31/21

EUA’s for Asymptomatic Screening & Serial Screening

*3 saliva

Collection Kit, 10 Molecular Home, 2

Antigen Home, 2 Antigen POC, 1

Serial Testing – 2 tests in 24-48 hours

Antigen Home, 11

*4 saliva Molecular POC, 38

Antigen POC, 12

*1 saliva

Screening (53)

Molecular POC, 9

Serial Screening (32)

Pandemic Total through 12/31/21

24 EUA’s for Respiratory Panels (Flu, RSV, etc.)

Molecular Respiratory Combination Tests (20) • • • • • • • • • • • • • • • • • • • •

Abbott Alinity m Resp-4-Plex Applied BioCode CoV-Flu Plus Assay* BD for BD MAX system BioFire Diagnostics Respiratory Panel 2.1 EZ Bio-Rad Reliance CDC Flu C2 Multiplex Assay Cepheid Xpert Xpress Ful/RSV Cepheid Xpert Xpress Flu/RSV Plus Exact Science Laboratories COVID-Flu Multiplex GenMark ePlex Respiratory Pathogen Panel 2 Hologic Aptima Labcorp SARS-CoV-2 & Influenza A/B Assay Luminex NxTAG Respiratory Pathogen Panel + SARS-CoV-2 NeuMoDx Flu A-B/RSV/SARS-CoV-2 Vantage Assay PerkinElmer Pkamp Respiratory SARS-CoV-2 Panel 1* QIAGEN GmbH QIAstat-Dx Respiratory SARS-CoV-2 Panel Quest RC COVID-19+Flu RT-PCR Roche cobas Roche cobas for use with Liat system Thermo Fisher TaqPath

New Q4*

Antigen Respiratory Combination Tests (3) • BD Veritor System for Rapid Detection of SARS-CoV-2 & Flu A+B • Princeton BioMeditech Corp. Status COVID-19/Flu • Quidel Sofia 2 Flu + SARS Antigen FIA Molecular Respiratory Combination Collection Kits (1) • Everlywell COVID-19 & Flu Test Home Collection Kit

Pandemic Total through 12/31/21

36 EUA’s for Testing of Pooled Samples  

POOL SIZE

CDC [RT-PCR Diagnostic Panel] Quest [SARSCoV-2 rRT-PCR]

• •

Quest [RC SARSCoV-2 Assay] Roche [cobas SARS-CoV-2]

• •

2 (1 Test) 4 (2 Tests) 5 (22 Tests) 6 (2 Tests) 7 (1 Test) BayCare [SARSCoV-2 RT PCR Assay]

BioFire [COVID-19 Test] Cepheid [Xpert Xpress SARS-CoV-2]

8 (2 Tests) 10 (4 Tests) 12 (2 Tests)

Poplar [TMA Pooling assay]

• Abbott [Alinity m SARS-CoV-2 assay] • OPTI SARS-CoV-2 RT-PCR Test • Amazon/STS Labs HoldCo [4 assays] • PerkinElmer [New COVID Nucleic Acid Detection • Applied BioCode [ SARS-CoV-2 Assay] Kit] • Enzo [AMPIPROBE SARS-CoV-2 Test System] • SML GENETREE [Ezplex SARS-CoV-2 G Kit] • Hologic [Aptima SARS-CoV-2 assay] • Thermo Fisher TaqPath • Hologic [Panther Fusion SARS-CoV-2 Assay] • UCSD [RC SARS-CoV-2 Assay] • Infinity BiologiX TaqPath SARS-CoV-2 Assay • Visby Medical COVID-19 • Labcorp [COVID-19 RT-PCR Test] • Yale School of Public Health SalivaDirect • Labcorp [Pixel Home Collection Kit] • Yale SalivaDirect for use with DTC Kits • LetsGetChecked Coronavirus (COVID-19) Test • LumiraDx [SARS-CoV-2 RNA STAR Complete]

• • • Broad Institute CRSP rtPCR Assay (Version 3) • Viracor Eurofins [SARS-CoV-2 assay] • Clinical Enterprise SARS-CoV-2 RT-PCR Assay • Biomeme SARS-CoV-2 RealTime RT-PCR Test

Quadrant Biosciences [Clarifi COVID-19 Test Kit] Verily [COVID-19 RTPCR Test]

Pandemic Total through 12/31/21

21 EUA’s for Independent Home Specimen Collection Kits Note: Does not include collection kits included with proprietary assays; only kits separately authorized with independent EUA’s

16 14

Number of Tests

12 10 8 6 4 2 0

Swab (14) 64% Rx 36% DTC

Rx: requires prescription DTC: direct to consumer

Saliva (7) 57% Rx 43% DTC

Pandemic Total through 12/31/21

21 EUA’s for Independent Home Specimen Collection Kits Note: Does not include collection kits included with proprietary assays; only kits separately authorized with independent EUA’s

Swab Collection Kits (14)

• Audere HealthPulse@home* • binx health At-Home Nasal Swab COVID-19 Sample Collection Kit • Clinical Enterprises EmpowerDX COVID-19 Home Collection Kit DTC • Color COVID-19 Self-Swab Collection Kit • Color COVID-19 Self-Swab Collection Kit DTC • Color COVID-19 Self-Swab Collection Kit with Saline • Everlywell COVID-19 Test Home Collection Kit • Everlywell COVID-19 Test Home Collection Kit DTC • Everlywell COVID-19 & Flu Test Home Collection Kit • GetMyDNA COVID-19 Test Home Collection Kit • Kroger Health COVID-19 Test Home Collection Kit • Kwokman Diagnostics COVID-19 Home Collection Kit • Quest Diagnostics Collection Kit for COVID-19* • RapidRona Self-Collection Kit

New Q4*

Saliva Collection Kits (7)

• DNA GenoTech OMNIgene·ORAL OM-505 and OME-505 (OMNIgene·ORAL) Saliva Collection Device • DNA GenoTech ORAcollect∙RNA OR-100 and ORAcollect∙RNA ORE-100 Saliva Collection Device • Phosphorus Diagnostics LLC Pinpoint by Phosphorus COVID19 Test Home Collection Kit DTC • Spectrum Solutions SDNA-1000 Saliva Collection Device • WREN Laboratories COVID-19 Saliva Test Collection Kit DTC • Yale School of Public Health SalivaDirect • Yale School of Public Health SalivaDirect DTC

Pandemic Total through 12/31/21

Research Use Only Tests 250

Molecular

Antibody

Number of Tests

200

150

100

Antigen

Other

50

0

Molecular 88% RTqPCR 9% Isothermal 2% Other

Antigen 67% Lateral Flow 33% ELISA

Antibody 48% Lateral Flow 52% ELISA

Other Collection Kits Flu/RSV Panels Pandemic Total through 12/31/21

EUA’s for Management of COVID-19 Patients IVDs for Management of COVID-19 Patients (4) - Roche Diagnostics Elecsys IL-6

(June 2020)

- Beckman Coulter, Inc. Access IL-6

(October 2020)

- Siemens Healthcare Diagnostics Inc. ADVIA Centaur IL6 Assay

(December 2020)

- BD Vacutainer Plus Citrate Plasma Tubes (UK Manufacturing Site)

(August 2021)

Pandemic Total through 12/31/21

New EUAs by Technology Q4 2021 (n=19) Total Q4 2021 New EUA’s 5 1

2

Comprehensive At-Home Tests Flu / RSV Combo Tests Lab / POC COVID only

4 3

Molecular Tests

Antigen Tests

2

2

Serology Tests

Collection Kits

New EUAs by Technology Q3 2021 (n=28) 0

3

Total Q3 2021 New EUA’s

10 Comprehensive At-Home Tests Flu / RSV Combo Tests 2

5

Lab / POC COVID only 5 3

Molecular Tests

Antigen Tests

Serology Tests

Collection Kits

New EUAs by Technology Q2 2021 (n=45) 1

Total Q2 2021 New EUA’s

6

Comprehensive At-Home Tests

15

Flu / RSV Combo Tests Lab / POC COVID only

2

8

9

5

Molecular Tests

Antigen Tests

Serology Tests

Collection Kits

New EUAs by Technology Q1 2021 (n=41)

1

Total Q1 2021 New EUA’s

6

Comprehensive At-Home Tests Flu / RSV Combo Tests

14

Lab / POC COVID only 10 3 1

3 Molecular Tests

Antigen Tests

Collection Kits are listed separately as their own category by Testing Commons

3 Serology Tests

Collection Kits

Timeline of EUA Issuances and Amendments by Type 1

1

2

4

3

3

1

2

1 3

2 6

7 5

2

1

4 1

2

1

1

2

2 2

9 4

8

13

25

9 6

32 1

17

1

5 8 3

3

1

2

4

3 4

5 5

14

2

3

2

8

1

1

1

2 2

4

3 3

28

20

19

21 2

8

8

Antibody

6

1

5

28

6

Antigen

4

6

6

Molecular

1 12

10

8

3

2

Flu/RSV

Collection Kit

1

Pandemic Total through 12/31/21

COVID-19 Diagnostics Related Legal Issues • Federal (U.S.)

• Regulatory – late 2021 – HHS/FDA make changes to EUA process for LDTs • Fraud / SEC violations – Early stage Dx companies running into billing / operations legal trouble • IP – NIH – Moderna disputing inventorship of vaccine patents • USPTO has issued approximately 130 COVID-19 diagnostic patents

• U.S. Supreme Court legal battle over OSHA vaccine-or-test federal mandate for private employers • ADA – fight over whether long-haul COVID-19 is a disability under ADA

• International

• Waiver of patent rights on an international scale • U.S. supports but has not yet waived rights • Currently contemplated for vaccine patents, but could be extended to Diagnostics

Acknowledgements I would like to thank the following people & organizations for their help and support: • ASU College of Health Solutions • Sarah Igoe, M.D. for her leadership on TestingCommons.com • Nate Wade, Ph.D., for his brilliant work and partnership as Co-PI • Michael Donovan, J.D., Ph.D. • Dean Deborah Helitzer, Sc.D. • ASU Decision Theater • The entire Decision Theater team including Sri Kandala, Ph.D. and Fangwu Wei, Ph.D. • The Rockefeller Foundation • For the enabling grant for TestingCommons.com and continued commitment to diagnostics education • Special thanks to Leah Perkinson Mara G. Aspinall – mara.aspinall@asu.edu Professor of Practice, Biomedical Diagnostics, College of Health Solutions, Arizona State University Advisor, The Rockefeller Foundation