Aacc 2013 booth rev

An industry leader and innovator in Infectious Disease Diagnostic Development, ZeptoMetrix Corporation (ZMC) is a fully integrated Biotechnology Company whose Products and Services support all phases of R&D, Assay Validation and Verification, Manufacturing, Regulatory Submissions and Test Kit Commercialization.

BUFFALO, NYCorporate Headquarters (Buffalo-Niagara Medical Campus)

Research & Development

21,000 sq. ft. 2 large Biological Level 3 Plus LaboratoriesISO 13485:2003 CertifiedCDC Select Agent LicenseUSDA Select Agent License

FRANKLIN, MAFDA Registered Manufacturing Facility

Distribution and Fulfillment Services, Biorepository 25,000 sq. ft.cGMP Compliant Manufacturing & Clinical Sample RepositorycGMP Compliant Testing LaboratoryISO 13485:2003 CertifiedFDA Registered Blood EstablishmentFDA Establishment LicenseIVD Controlled and Manufactured Product Facility

Research and Development

Purified Microorganisms (Viruses, Bacteria, Fungii) and Derivatives (Sucrose Purified, Titered Culture Fluids, Lysates, Purified DNA/RNA)Serum Spiked Organisms for Regulatory Studies.

Virology and Microbiology Service Laboratory, Infectivity Validations, Growth Studies, TCID50, Custom Projects

Biorepository containing >1,000,000 samples (Disease State Samples, Normal Human Serum, Cancer Markers, Chemistries, AutoImmune, Pregnancy (1st, 2nd and 3rd Trimesters)

Seroconversion Panels - HIV, HBV, HCV and EBV

ELISA Kits - HIV p24 Ag, SIV, HTLV, Human, Mouse & Bovine IgG, IgM

Western Blots - HIV, SIV, HTLV, I/II, Helico Blot 2.1

Infectious Disease Research Solutions

Manufacturing

Bulk Disease State and Normal Human Plasma and Serum

Dilutional Base Matricies for Serology, Antigen and Molecular based Assays (Natural and Synthetic)

OEM Control and Calibrator Formulations (Serology or Molecular): Bulk or Finished Vials

In Process and Final Product Release Panels Product Validation

CLIA Validation Panels for Serology (SeroDetect) and Molecular Platforms (NATtrol™ ). Sensitivity/Specificity , Range Validation and Interfering Substance Panels

NATtrol™ External Run Controls for Molecular Testing of Viral, Bacterial and Fungal Markers (Multiple Species and Concentrations)

Rapid Test Controls for Serological and Antigen based Assays


Regulatory Submissions

Assay Validation and Verification Studies

Laboratory Service Testing, Sensitivity/Specificity

Test Kit Commercialization

Marketing, Training, Proficiency and Reference Panel Development

External Run Controls

BioStor™ BioRepository and Fulfillment Services


Additional ZeptoMetrix Product/Service Offerings

Serological and PCR/NAT Controls and Calibrators

Virology and Oxidative Stress Service Laboratory Testing

Microorganisms and Derivatives

Proficiency and Reference Panels

Research Test Kits

Test Kit Development and Validation Services

Clinical Specimens and Repository Services

“Although Manufacturers may assist Laboratories by providing quality control instructions, the Laboratory is ultimately responsible for the performance of appropriate quality control procedures, including the documentation and interpretation of quality control data.

Under subpart M, the Director is responsible for ensuring that quality control and quality assessment programs are established and maintained….”

See: §493.1256(d)

RESPONSIBILITYACCOUNTABILITYLIABILITY

Appropriate Frequency of QC Testing Required for Molecular Amplification Tests

Every Lab must run 2 levels of External QC Materials each day that it performs a nonwaived test

Amplification Tests are excluded from equivalent QC procedures*i.e. 10 or 30 days of acceptable QC results with two levels

of External Controls does not reduce the QC testing requirements

* Brochure #4—Equivalent Quality Control Procedures (CLIA)

Acceptable Forms of External QC Materials*

Commercially Prepared ControlsIn-House Prepared ControlsReference or Controls Strains of MicroorganismsMultiple Calibrators of Separate Lot Numbers and

Concentrations than those used to Calibrate the System

Previously Tested Patient Specimens provided the Laboratory determines the acceptable performance level for the patient specimens

Proficiency Testing Specimens for which the results have been confirmedLabs should confirm that they are allowed to

maintain PT samples. * §493.1256(c)

Standard: Control Procedures

(c) The control procedures must—(c)(1) Detect immediate errors that occur due to test system failure, adverse environmental conditions, and operator performance.(c)(2) Monitor over time the accuracy and precision of test performance that may be influenced by changes in test system performance and environmental conditions, and variance in operator performance. * §493.1256(c)

CLIA requirements for External Run Controls

Need to be run at Regular Intervals (every Run, every Day or Weekly) based on the Assay Configuration

Two Levels of Challenge (Low and Medium Reactivity) are necessary

Formulation needs to be as close to a True Clinical Specimen as possible

Run with Same Testing Protocol as a Clinical Specimen

Commutability with Serum, Plasma and other Biological Fluids

Validation vs. VerificationValidation

• “confirmation, through the provision of objective evidence, that requirements for a specific intended use or application have been fulfilled” (ISO 9000)

• validation determines that the correct test is being utilized

Verification• “confirmation, through the provision of objective

evidence, that specified requirements have been fulfilled” (ISO 9000)

• verification determines that the test is being utilized correctly

Arch Pathol Lab Med. 2009;133:743-755, Jennings, Van Deerlin and Gulley; CAP Molecular Pathology Resource Committee

CLIA Testing Requirements by Test Type

LDT-(Home Brew) LDT-ASR

Modified FDA-Cleared

FDA-Cleared

RiskLab Testing Requirements

High High

LowLow

CLIA Verification of Analytical Performance Characteristics

Verification ReportWhen: Initial Setup and at Regular Intervals for

assessment of technical variability: reagents, equipment, users, calibration, etc.

Analytical Sensitivity (Positive Agreement)Analytical Specificity (Negative Agreement)Precision, day to day, user to user, instrument to

instrumentInterfering Substances: Matrix Effects, Clinical

Specimens, CommutabilityCLSI EP12-A Qualitative Test PerformanceCLSI EP15-A2 Precision

Additional Requirements forMolecular Test Launch

• Completed Verification Report• Written Assay Procedures• Written Reports and Forms• Training Checklist• Competency of Staff Documented• MSDS Forms on file• Billing and Testing Codes Established• Completed Training• Equipment Maintenance and Calibration

Schedule• Enrollment in a Proficiency Program (CAP)

Background:HIV, HCV, HBV Bloodscreening External Run Controls

Theory : Microorganisms require discrete Surface Protein Receptors to bind to and penetrate a host cell.

Hypothesis:When we modify those Surface Proteins such that the Microorganism can no longer bind to a host cell, then the Microorganism should become noninfectiousand…When we modify those Surface Proteins without damaging the inner Nucleic Acids, then the modified Microorganism should still function in a Molecular based Assay.

Conclusion:Two highly controlled Biomedical Procedures are used to modify the Surface Proteins and render the Microorganism noninfectious.

NATtrol™ Molecular Controls

Product Highlights:Non-Infectious

SafePurified Serum Protein Matrix

Whole Intact OrganismWorks across all PlatformsMimics a true Clinical SpecimenContains the entire genome of the Microorganism,

not Synthetic sequences of RNA

Full ProcessControls for all processes involved with

Extraction & Amplification of the Microorganism

Refrigerator StableSimple storage and quick usage v. FrozenRequires 2 °C to 8 °C unlike most that demand-20 °C Gel Pack v. Dry Ice ($avings during shipping)

NATtrol™ Molecular Controls

Product Highlights:1-2 year Stability

Superior Shelf Life Longer Availability/Reuse Capabilities

Flexible Availability Available as Individual or Multiplexed

Controls

Compatible Biotechnology Process is viable for Virus, Bacteria, Fungi,

Parasite and Bacteriophage Organisms.

Broad Patent Coverage Protected Technology

NATtrol™ Molecular Controls (cont.)

Currently Available Viruses• Adenovirus• Banzi• BK• Bovine Leukemia• Bovine Viral Diarrhea (BVDV)• Chikungunya• Coronavirus• Coxsackievirus• Cytomegalovirus (CMV)• Dengue 1, 2, 3, 4• Echovirus• Enterovirus• Epstein-Barr (EBV)• Hepatitis A (HAV)• Hepatitis B (HBV)• Hepatitis C (HCV)• Herpes Simplex (HSV 1, 2)• Human Herpes (HHV6, 7, 8)• Human Immunodeficiency (HIV)• Human Metapneumovirus (hMPV)• Human T-lymphotrophic (HTLV)

• Ilheus• Influenza A• Influenza B• Measles• Minute Virus of Mice (MVM)• Mouse Hepatitis (MHV)• Mouse Mammary Tumor (MMTV)• Mumps• Parainfluenza• Parechovirus• Respiratory Syncytial (RSV)• Rhinovirus• Rotavirus• Rubella• Saint Louis Encephalitis (SLEV)• Severe Acute Respiratory Syndrome

(SARS)• Simian Immunodeficiency (SIV)• Varicella Zoster (VZV)• West Nile (WNV)• Yellow Fever• Zika

Currently Available Bacteria, Fungi & Parasites• Acinetobacter• Aspergillus• Bacillus• Bacteroides• Bifidobacterium• Bordetella• Brucella• Burkholderia• Campylobacter• Candida• Chlamydia• Citrobacter• Clostridium• Corynebacterium• Cronobacter• Cryptococcus• Cunninghamella• Entamoeba• Enterobacter

• Enterococcus• Escherichia • Francisella• Fusarium• Gardnerella• Haemophilus• Helicobacter• Klebsiella• Kocuria• Lactobacillus• Legionella• Listeria• Micrococcus• Moraxella• Mucor• Mycobacterium• Mycoplasma• Neisseria• Nocardia

• Prevotella• Proteus• Pseudomonas• Rhizobium• Rhizopus• Rothia• Saccharomyces• Salmonella• Scedosporidium• Serratia• Shigella• Staphylococcus• Stenotrophomonas• Streptococcus• Toxoplasma• Tremella• Trichomonas• Vibrio• Yersinia

Recombinant Controls• Blastomyces dermatitidis, assay specific• Coccidioides immitis, assay specific• Coronavirus HKU, assay specific• Cryptosporidium parvum, assay specific and native organism

control is in development• Cyclospora cayetanensis, assay specific recombinant in

development• Escherichia coli, O157, assay specific• Giardia lamblia, assay specific and native organism control is in

development• Histoplasma capsulatum, assay specific• Norovirus group I• Norovirus group II• Pneumocystis jiroveci, assay specific• Sapovirus, assay specific recombinant in development• stx1 and stx2, can be exported out of the US, assay specific• Vibrio cholerae, can be exported out of the US, assay specific

Recent ZeptoMetrix Highlights

Select Agent Regulations Exemption

SARS-CoV---Select Agent as of 12/4/2012.

In February 2013 the Centers of Disease Control and Prevention (CDC), Division of Select Agents and Toxins (DSAT) has determined and approved an exclusion for ZeptoMetrix Corporation’s NATtrol™-treated SARS-CoV Molecular Controls from the Select Agent Regulations, including those regarding the possession, use and transfer of select agents (42 C.F.R. 73 and 9 C.F.R. 121).


NATtrol™ RP Multimarker Control# NATRPC-BIO

Designed to evaluate/monitor the performance of the FilmArray™ RP Assay

Whole Intact Organisms Mimics true Clinical Specimens

Contains the entire genome of each Microorganism

Full ProcessControls for all processes

involved with Extraction & Amplification of the Microorganism

Refrigerator StableNot frozenSimple storage /quick usage Requires 2 °C to 8 °C storageGel Pack v. Dry Ice

Superior Stability Superior Shelf Life Longer Availability/Reuse

Capabilities

Bacterial Targets


NATtrol™ EBV Linearity Panel # NATEBV-LIN

Whole Intact Organism Mimics a true Clinical Specimen

Contains the entire genome of the viral particle


involved with Extraction & Amplification of the Microorganism



Capabilities


NATtrol™ EBV External Run Controls # NATEBV-ERCL and NATEBV-ERCM

Whole Intact Organism Mimics a true Clinical Specimen

Contains the entire genome of the viral particle


involved with Extraction & Amplification of the microorganism



Capabilities

Molecular Testing

Luminex xTAG Molecular

Test Control Panel

RVP Pending Yes (NATRVP-1,2 & 3)

Enterics Pending Pending

Biofire FilmArray

Test Control Panel

Res. Panel Yes (NATRPC-BIO) Yes (NATRVP-IDI)

Roche Light Cycler 2.0/480

Test Control Panel

HSV 1/2

(NATHSV1-0001; NATHSV1-0002; NATHSV1-0003; NATHSV1-0004; NATHSV1-0005; NATHSV2-0001; NATHSV2-0002; NATHSV2-0003; NATHSV2-0004; NATHSV2-0005)

Pending

GenMark eSensor XT

Test Control Panel

Res. Panel Pending Yes (NATRVP-3)

HCV Genotype Pending Pending

BD ProbeTec

Test Control Panel

CT/NGYes (NATCT(434)-ERCM and

NATCT(D-UW3)-ERCM;NATNG-ERCM)

Pending

Molecular Testing

Roche Ampliprep - Taqman

Test Control Panel

HIV Yes (NATHIV1-ERCL; ERCM) Yes (NATHIV1-LIN)

HBV Yes (NATHBV-0001; NATHBV-0002; NATHBV-0003; NATHBV-0006) Pending

HCV Yes (NATHCV-0001; NATHCV-0002; NATHCV-0003; NATHCV-0004; NATHCV-0005) Pending

CMV Yes (NATCMV-ERCL;ERCM) Yes (NATCMV-LIN)

CT/NG Yes (NATCT(434)-ERCL;ERCM and NATCT(D-UW3)-ERCL;ERCM) Pending

Cepheid

Test Control Panel

MRSA Yes (NATMRSA-6MC and NATMSSA-6MC)Yes

(NATMRSA/SAP-C and NATMRSAP-C)

VZV Yes (NATVZV-001, NATVZV-002, NATVZV-003, NATVZV-004, NATVZV-005) Pending

CT/NG Yes (NATCT(434)-6MC and NATNG-6MC) Yes (NATCTNGP-C)

GBS Yes (NATSAG-6MC) Pending

FLU A/B Yes (NATFLUA/B-6MC and NATFLUAH1N1-6MC) Yes (NATFVP-C)

C. diff Yes (CDI-6MC) Yes (NATCDIP-C)

Molecular Testing

Meridian Illumigene

Test Control Panel

C. diff Yes (NATCDI (NAP1)-ERCL; ERCM) Pending

GBS Yes (NATSAG-6MC) Pending

Focus Simplexa

Test Control Panel

Flu A/B Yes (NATFLUAH1-ERCL;ERCM and NATFLUB-ERCL; ERCM) Pending

H1N1 (2009) Yes (NATFLUAH1N1-ERCL;ERCM) Pending

CMV Yes (NATCMV-ERCL;ERCM) Yes (NATCMV-LIN)

C. diff Yes (NATCDI(NAP1)-ERCL;ERCM) Pending

Nanosphere SP

Test Control Panel

Res. Panel Pending Yes (NATFVP-NNS)

GP/BC Pending Yes (NATBC/GP-NNS)

C. Diff Yes (NATCDI(NAP1)-ERCL; ERCM) Pending

Siemens Versant 440

Test Control Panel

HIV Yes (NATHIV1-ERCL; ERCM) Yes (NATHIV1-LIN)

HCVYes (NATHCV-0001; NATHCV-0002;

NATHCV-0003; NATHCV-0004; NATHCV-0005)

Pending

Serological Testing

Abbott Architect Ortho eci Avidia Centaur (Siemens)

Panel

SeroDetect HIV-Ab

SeroDetect HBsAg

SeroDetect Anti-HBs

SeroDetect Hbcore

SeroDetect HCV

SeroDetect HTLV

SeroDetect HCV-Ab M

ZeptoMetrix Corporation878 Main Street, Buffalo, NY 14202

716-882-092025 Kenwood Circle, Franklin, MA 02038

508-553-5800

Gregory R. Chiklis, Ph. D.President and Chief Operating Officer

[email protected]

Karuna Sharma, Ph. D.Senior Director & Chief Science Officer

[email protected]

Peter Trabold, Ph. D., MBADirector, Business Development

[email protected]

Michael A. HershfieldDirector, Sales & Marketing

[email protected]