Transcript: New from BookNet Canada for 2024: BNC CataList - Tech Forum 2024
Aacc 2013 booth rev
1.
2.
3. 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.
4. BUFFALO, NY
Corporate Headquarters (Buffalo-Niagara Medical Campus)
Research & Development
21,000 sq. ft.
2 large Biological Level 3 Plus Laboratories
ISO 13485:2003 Certified
CDC Select Agent License
USDA Select Agent License
FRANKLIN, MA
FDA Registered Manufacturing Facility
Distribution and Fulfillment Services, Biorepository
25,000 sq. ft.
cGMP Compliant Manufacturing & Clinical Sample Repository
cGMP Compliant Testing Laboratory
ISO 13485:2003 Certified
FDA Registered Blood Establishment
FDA Establishment License
IVD Controlled and Manufactured Product Facility
5.
6.
7. 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
8. 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
Infectious Disease Research Solutions
9. 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
Infectious Disease Research Solutions
10. 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
11.
12.
13. “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
14. 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)
15. Acceptable Forms of External QC Materials*
Commercially Prepared Controls
In-House Prepared Controls
Reference or Controls Strains of Microorganisms
Multiple 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 confirmed
Labs should confirm that they are allowed to maintain PT
samples.
* §493.1256(c)
16. 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)
17.
18. 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
19. Validation vs. Verification
Validation
• “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
20. CLIA Testing Requirements by Test Type
LDT-(Home Brew)
LDT-ASR
Modified FDA-Cleared
FDA-Cleared
Risk
Lab
Testing
Requirements
High High
LowLow
21.
22.
23. CLIA Verification of
Analytical Performance Characteristics
Verification Report
When: 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 instrument
Interfering Substances: Matrix Effects, Clinical
Specimens, Commutability
CLSI EP12-A Qualitative Test Performance
CLSI EP15-A2 Precision
24. Additional Requirements for
Molecular 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)
25.
26.
27. 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 noninfectious
and…
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
28. Product Highlights:
Non-Infectious
Safe
Purified Serum Protein Matrix
Whole Intact Organism
Works across all Platforms
Mimics a true Clinical Specimen
Contains the entire genome of the
Microorganism, not Synthetic sequences
of RNA
Full Process
Controls for all processes involved with
Extraction & Amplification of the Microorganism
Refrigerator Stable
Simple storage and quick usage v. Frozen
Requires 2 °C to 8 °C unlike most that demand-20 °C
NATtrol™ Molecular Controls
29. 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.)
30.
31. 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
33. 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
34.
35.
36. 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).
37. Recent ZeptoMetrix Highlights
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 Process
Controls for all processes involved with
Extraction & Amplification of the
Microorganism
Refrigerator Stable
Not frozen
Simple storage /quick usage
Requires 2 °C to 8 °C storage
Gel Pack v. Dry Ice
Superior Stability
Superior Shelf Life
Longer Availability/Reuse Capabilities
Bacterial Targets
38. Recent ZeptoMetrix Highlights
NATtrol™ EBV Linearity Panel
# NATEBV-LIN
Whole Intact Organism
Mimics a true Clinical Specimen
Contains the entire genome of the viral particle
Full Process
Controls for all processes involved with
Extraction & Amplification of the
Microorganism
Refrigerator Stable
Not frozen
Simple storage /quick usage
Requires 2 °C to 8 °C storage
Gel Pack v. Dry Ice
Superior Stability
Superior Shelf Life
Longer Availability/Reuse Capabilities
39. Recent ZeptoMetrix Highlights
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
Full Process
Controls for all processes involved with
Extraction & Amplification of the
microorganism
Refrigerator Stable
Not frozen
Simple storage /quick usage
Requires 2 °C to 8 °C storage
Gel Pack v. Dry Ice
Superior Stability
Superior Shelf Life
Longer Availability/Reuse Capabilities
40.
41. MolecularTesting
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/NG
Yes (NATCT(434)-ERCM and
NATCT(D-UW3)-ERCM;
NATNG-ERCM)
Pending
42. MolecularTesting
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)
43. MolecularTesting
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)
HCV
Yes (NATHCV-0001; NATHCV-0002;
NATHCV-0003; NATHCV-0004;
NATHCV-0005)
Pending
45. ZeptoMetrix Corporation
878 Main Street, Buffalo, NY 14202
716-882-0920
25 Kenwood Circle, Franklin, MA 02038
508-553-5800
Gregory R. Chiklis, Ph. D.
President and Chief Operating Officer
chiklis@zeptometrix.com
Karuna Sharma, Ph. D.
Senior Director & Chief Science Officer
karuna_s@zeptometrix.com
Peter Trabold, Ph. D., MBA
Director, Business Development
peter_t@zeptometrix.com
Michael A. Hershfield
Director, Sales & Marketing
mhershfield@zeptometrix.com
Editor's Notes
Cumitech (ASM) and CLSI vs. FDA, CAP and ISO have opposing definitions of verification and validation. The FDA/CAP definitions are present here.
