Diagnostic Assay-Target Product Profile
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Diagnostic Assay–
Target Product Profile
Diagnostic Assay: Quantitative glucose-6-phosphate
dehydrogenase (G6PD) activity
Product: Point-of-care test for G6PD deficiency
Version: 8.5
Completed: 4/22/2021G6PD TPP Version: 8.5 April 22, 2021 - Page 2
Abbreviations
CLIA Clinical Laboratory Improvement Amendments
EDTA ethylene diamine tetra acetic acid
FDA US Food and Drug Administration
G6PD glucose-6-phosphate dehydrogenase
GSK GlaxoSmithKline
Hb hemoglobin
ICH International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use
IFU instructions for use
NADPH nicotinamide adenine dinucleotide phosphate
P. falciparum Plasmodium falciparum
P. vivax Plasmodium vivax
QC quality control
RDT rapid diagnostic test
TPP target product profile
WHO PQ World Health Program prequalificationG6PD TPP Version: 8.5 April 22, 2021 - Page 3 Context Defining the need for a quantitative point-of-care G6PD diagnostic test for safe treatment of Plasmodium vivax infection with an 8-aminoquinoline Clinical need: Tafenoquine and primaquine are 8-aminoquinoline–based drugs that completely clear the human body of Plasmodium (P.) vivax parasites (radical cure). As 8-aminoquinolines, primaquine, and tafenoquine represent a risk to subjects with a common genetic trait manifested as deficiency in glucose-6-phosphate dehydrogenase (G6PD) activity. A major barrier to wide-scale adoption of radical cure is toxicity in people with G6PD deficiency. Whereas all people exposed to 8-aminoquinolines experience some drop in hemoglobin concentrations, people with G6PD deficiency are more likely to experience severe hemolysis, leading to severe hemolytic anemia and, potentially, death. As such, tafenoquine and primaquine should be administered only to subjects who are not G6PD deficient or who have sufficient G6PD activity in their red blood cells that exposure to the drug does not represent a risk. Test description: A diagnostic test that determines whether a patient presenting with P. vivax infection has sufficient G6PD activity in their red blood cells to be treated with primaquine or tafenoquine is required to make the drug widely and safely available. Currently, the only reliable tests for G6PD deficiency are laboratory based and require significant expertise to run, as well as laboratory resources. Point-of-care tests for G6PD deficiency would permit treatment decision-making to happen where people seek health care—at primary health care facilities, dispensaries, and even through trained health care workers. The test should have similar workflow and resource requirements as malaria rapid diagnostic tests (RDTs).
G6PD TPP Version: 8.5 April 22, 2021 - Page 4
Executive Summary Table
Variable Targeted requirement Optimistic specification
1. Product use summary/medical need/differentiation strategy
The rapid diagnostic test is intended for
An in vitro enzyme test for the semi- the simultaneous quantitative
quantitative determination of glucose- measurement of red blood cell G6PD
6-phosphate dehydrogenase (G6PD) activity and hemoglobin (Hb) in finger-stick
enzyme activity in finger-stick blood (capillary) or venous (EDTA-
and ethylene diamine tetra acetic acid anticoagulated) whole blood.
(EDTA) anticoagulated blood. For in
vitro diagnostic use only. The test will provide results expressed as
the ratio of units per deciliter of G6PD
The test will provide results expressed activity per gram of hemoglobin per
as the ratio of units per deciliter of deciliter (G6PD U/g Hb) to normalize
1.1 Intended use(s)
G6PD activity per gram of hemoglobin G6PD activity for hemoglobin level. The
per deciliter (G6PD U/g Hb) to “G6PD plus Hb” system is intended for
normalize G6PD activity for differentiating normal from deficient G6PD
hemoglobin level. The “G6PD plus activity levels in whole blood in order to
Hb” system is intended for identify individuals with G6PD deficiency.
differentiating normal from deficient
G6PD activity levels in whole blood in The test will also provide a stand-alone
order to identify individuals with G6PD quantitative hemoglobin measurement in
deficiency. g/dL from fingerstick (capillary) or venous
(EDTA-anticoagulated) whole blood.
Quantitative determination of G6PD
Determination of G6PD enzymatic
enzymatic activity and hemoglobin
activities in whole blood to inform
concentration in whole blood to inform
radical cure treatment with
treatment with tafenoquine and
tafenoquine of symptomatic patients
primaquine of symptomatic patients
1.2 Examples of use infected with P. vivax. Test will be able
infected with P. vivax. Also, in support of
to discriminate normal G6PD levels
P. vivax elimination, can be used in mass
(>70%) from deficient (≤30%) and
screening and treatment of asymptomatic
borderline (>30%–70%). Performance
individuals. The test supports other
will be assessed for >30-70%.
national G6PD testing requirements.
Symptomatic P. vivax–infected children
Symptomatic P. vivax–infected
and adults. Symptomatic and
1.3 Target population children ≥6 months of age and adults
asymptomatic individuals in P. vivax
of both genders.
malaria elimination setting.
All health care settings where people
Primary health care facilities and
1.4 Infrastructure level access malaria care, including village
mobile clinics with trained staff.
health care workers.G6PD TPP Version: 8.5 April 22, 2021 - Page 5
Variable Targeted requirement Optimistic specification
Medical or laboratory qualified worker
1.5 End user (e.g., primary care level/laboratory Community health care worker.
technician/ health care worker).
2. Design
Possible battery-operated reading
2.1 Format/
system, temperature monitor,
instrumentation No instrumentation required.
hemoglobin concentration measuring
requirements
capability.
Erythrocytic or red blood cell G6PD
Erythrocytic or red blood cell G6PD
activity. NADPH concentration or other
activity. Nicotinamide adenine
validated analytes that indicate G6PD
dinucleotide phosphate (NADPH)
2.2 Target analyte enzyme activity and hemoglobin
concentration or other validated
concentration. Analytes indicative of risk
analytes that indicate G6PD enzyme
of hemolysis on exposure to 8-
activity.
aminoquinolines.
If the output of the test is hemoglobin
concentration corrected, the additional
2.3 Additional analyte Same.
analyte is either hemoglobin
concentration or hematocrit.
Venous whole blood collected in Venous whole blood collected in
2.4 Sample type anticoagulant EDTA and capillary anticoagulant EDTA/heparin/citrate and
blood from finger-stick. capillary blood from finger-stick.
Finger-stick, prepared in one or two
2.5 Sample collection and steps (buffer and lysis). Venous blood Finger-stick and venous blood with no
processing prepared in one or two steps (buffer preparation steps.
and lysis).G6PD TPP Version: 8.5 April 22, 2021 - Page 6
Variable Targeted requirement Optimistic specification
2.9 Portability Highly portable. Same.
Universal blood safety precautions to
2.10 Safety Same.
be observed by the user.
3. Performance
The test will provide results expressed
as the ratio of units per deciliter of The test will provide results expressed as
G6PD activity per gram of hemoglobin the ratio of units per deciliter of G6PD
per deciliter (G6PD U/g Hb) to activity per gram of hemoglobin per
normalize G6PD activity for deciliter (G6PD U/g Hb) to normalize
hemoglobin level. The “G6PD plus G6PD activity for hemoglobin level. The
Hb” system is intended for “G6PD plus Hb” system is intended for
differentiating normal from deficient differentiating normal from deficient G6PD
G6PD activity levels in whole blood to activity levels in whole blood to identify
3.1 Assay output
identify individuals with G6PD individuals with G6PD deficiency.
deficiency.
The test will also provide a stand-alone
The test will also provide a stand- quantitative hemoglobin measurement in
alone quantitative hemoglobin g/dL from finger-stick (capillary) and
measurement in g/dL from finger-stick venous whole blood collected in
(capillary) and venous whole blood anticoagulant EDTA/heparin/ citrate.
collected in anticoagulant EDTA.
G6PD: 0.4 U/g Hb (i.e., equivalent to
Trinity reference method or Pointe
G6PD:G6PD TPP Version: 8.5 April 22, 2021 - Page 7
Variable Targeted requirement Optimistic specification
Total imprecision ≤8%.
Display of G6PD and Hb results will
be rounded to first decimal place.
CV≤10% for G6PD enzyme activity >7
U/g Hb;
3.4 Precision Same.
SD ≤ ±1.0 U/g Hb for G6PD enzyme
activity ≤7 U/g Hb.
Variation of Hb within the medically
allowable error for Hb (7 U/g Hb; SD ≤ ±1.0 U/g Hb
accuracy relative to for G6PD enzyme activity ≤7 U/g Hb. Same.
reference method
HB method must be within the
medically allowable error for Hb (99%
3.6 Diagnostic of severe deficient cases (95% of cases withG6PD TPP Version: 8.5 April 22, 2021 - Page 8
Variable Targeted requirement Optimistic specification
6 results per hour (10 minutes to
3.8 Throughput 12 results per hour (5 minutes to results).
results).
Assay: 36 months at temperatures
between 2°C and 40°C; stable for 2 weeks
Assay: 18 months at temperatures at 50°C; time-temperature monitors
3.9 Target shelf life/ between 2°C and 40°C and relative included on each kit as per International
stability humidity of 75% ± 5% (as per test Conference on Harmonisation (ICH), and
operating range). relative humidity of 75% ± 5% (as per test
operating range).
No more than three steps, with no timed
3.10 Complexity: number
steps.
of steps required, No more than one timed step; total
Complexity compatible for Clinical
excluding sample less than five steps.
Laboratory Improvement Amendments
collection
(CLIA) waiver.
3.11 Operating 20°C–37°C, 30%–75% non- 18°C–40°C, 20%–90% non-condensing
temperature condensing humidity. humidity.
4. Validation/configuration/format/other
G6PD: Trinity Quantitative G-6-PDH
Kit 345-A or Pointe Scientific Kit
(CATALOG #G7583) since both are
4.1 Reference methods FDA-510(k)-cleared test methods. Same.
(Any other method needs validation by
PATH).
Hb: HemoCue is the reference test.
1,000 test results minimum will be
4.2 Data storage Same.
stored in the battery-operated device.
Stored test results can be accessed Stored test results can be accessed from
4.3 Data transfer/access from the device by USB cable or flash the device by USB cable or flash drive and
drive. secure wireless data exchange option.
Leverages appropriate HL7 FHIR
4.4 Data communication/ XML/JSON data structure used for
resources and adhere to appropriate IHE
standards results.
profiles.
G6PD measurement is recorded on
4.5 Recorded the device with sample ID and/or All test result measurements associated
data/metadata hemoglobin measurement where with a test run are recorded on the device.
applicable.
Ability to update firmware in the field
4.6 Firmware updates Same.
by authorized user.G6PD TPP Version: 8.5 April 22, 2021 - Page 9
Variable Targeted requirement Optimistic specification
World Health Organization Prequalification
(WHO PQ) recommends the product to
endure simulated extreme stress
Same as 3.9: Shipping simulation
conditions, ensuring that application of
4.7 Shipping conditions testing to conform to applicable
those conditions is consistent and
requirements of ASTM D4169-05.
controlled as per ISO 23640:2011, CLSI
EP25-A, WHO TGS-2, and ASTM D4169-
14.
One or less days for any level of
provider to achieve proficiency.
Language-appropriate training
materials, results guide, and job aids
Same, plus one hour for health care
4.8 Training requirements should be made available. Users
workers familiar with RDTs.
score a minimum of 85% according to
a standard proficiency assessment of
product label comprehension and
results interpretation.
Possible battery-operated G6PD
4.9 Instrumentation
reading system, temperature No instrumentation required.
requirements
correction, Hb measuring device.
4.10 Instrumentation Small equipment close to palm size
Comparable to handheld glucose monitor.
weight and size weighing less than one pound.
4.11 Instrument Manufacturer provides all required
Internal factory calibration.
calibration calibration biologics/materials.
4.12 Instrument service
None required for a period of 2 years. None required for a period of 3 years.
and support
Does not include material that cannot
4.13 Waste disposal be disposed of in the normal Same.
laboratory waste streams.
Possible battery with a battery life of
4.14 Power requirements None.
10 hours.
Self-contained kit operates
4.15 Water requirements None.
independent of water.
Demonstrated compatibility with
commercially available controls. IFU
must contain QC section with clear Diagnostic test manufacturer provides
4.16 Quality controls language of when and how to perform controls configured appropriately for
QC of the test. The suggested intended use.
approach must be practical for the
intended use of this TPP.G6PD TPP Version: 8.5 April 22, 2021 - Page 10
Variable Targeted requirement Optimistic specification
5. Product costs and channels to market
Disposable:
≤US$ 3.00 Disposable:
≤US$2.50 at scale ≤US$ 1.00
5.1 Target price ex works
Instrumentation: Instrumentation:
A reader cost of ≤US$ 380 A reader cost of ≤US$ 200
≤US$250 at scale
All countries with P. vivax radical cure
5.2 Target launch All countries with P. vivax radical cure in
in national malaria policy. Prioritization
countries national malaria policy.
to be determined.
CE-IVDR and WHO prequalification.
5.3 Product registration For US manufacturer, FDA-510(k).
Same.
path ISO 13485 certified Quality
Management System.
To be determined. National health
care system supply chain or supply
5.4 Channels to market Same.
chain of Global Fund to Fight AIDS,
Tuberculosis and Malaria.
Mailing Address Street Address path.org
PO Box 900922 2201 Westlake Avenue info@path.org
Seattle, WA 98109 USA Suite 200
Seattle, WA 98121 USAYou can also read
