WHO Prequalification of In Vitro Diagnostics PUBLIC REPORT

PQDx 0226-032-00 WHO PQ Public Report July 2020, version 6.0

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WHO Prequalification of In Vitro Diagnostics

PUBLIC REPORT

Product: m-PIMA HIV-1/2 Detect1 WHO reference number: PQDx 0226-032-00

m-PIMA HIV-1/2 Detect assay with product codes 27011R050, 27011R010 and 27030R001, manufactured by Abbott Rapid Diagnostics Jena GmbH2, CE marked regulatory version, was accepted for the WHO list of prequalified in vitro diagnostics and was listed on 13 June 2016.

Summary of WHO prequalification assessment for m-PIMA HIV-1/2 Detect assay

Date Outcome PQ listing 13-Jun-2016 listed Dossier review 18-Dec-2015 MR Site inspection(s) of quality management system 16-18-Jul-2018 MR Laboratory evaluation of performance and operational characteristics

14-Aug-2015 to 11-May-2016

MR

MR: Meets requirements Report amendments and/or product changes This public report has since been amended. Amendments may have arisen because of changes to the prequalified product for which WHO has been notified and has undertaken a review. Amendments to the report are summarized in the following table, and details of each amendment are provided below.

Version Summary of amendment Date of report amendment

3.0 To reflect fulfillment of an outstanding commitment to WHO prequalification. Commitment was on the instructions for use to be clear as per WHO’s requirement.

2-Sep-2016

4.0 Rebranding of products Alere q HIV-1/2 Detect (test cartridges, and accessory products) and Alere q analyzer to m-PIMA HIV-1/2 Detect and m-PIMA Analyser, and to update the products codes of the rebranded

30-Jul-2019

1 Please note the name of product Alere q HIV-1/2 Detect and Alere q instrument products were changed to m-PIMA HIV-1/2 Detect on 3 October 2018. 2 Manufacturer name changed from Alere Technologies GmbH to Abbott Rapid Diagnostics Jena GmbH.


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products and to reflect the latest version of the IFU. Minor editing of the performance evaluation part.

5.0 1. An additional kit insert containing further clarification (incl. pictures) on the correct interpretation of test results is to be included in all Alere q / m-PIMA HIV-1/2 Detect test kits. 2. Software and IFU change to modify the test report layout. A summary line is to be inserted indicating the overall test result in addition to the individual results for HIV-1 M/N, HIV-1 O, and HIV-2. 3. Change in the release QC procedure comprising modified analyte concentrations, new sampling plans for sensitivity and invalid test rate, and the removal of test group 3.

12-Mar-2020

6.0 The Manufacturer changed its name and address from Alere Technologies GmbH, Löbstedter Strasse 103-105, 07749 Jena, Germany to Abbott Rapid Diagnostics Jena GmbH, Orlaweg 1, D-07743 Jena, Germany. The EU notified body was changed from mdc to TÜV SÜD Product Service GmbH. Revision of product labels and IFUs.

13-Jul-2020

Intended use: According to the claim of intended use from Abbott Rapid Diagnostics Jena GmbH, “the m-PIMA HIV-1/2 Detect test is a qualitative nucleic acid amplification test for the detection of Human Immunodeficiency Virus (HIV) type 1 groups M/N and O, and type 2 RNA in human whole blood and plasma samples. The test can be used in laboratory as well as non-laboratory environments. The m-PIMA HIV-1/2 Detect test is intended for in vitro diagnostic use. The m-PIMA HIV-1/2 Detect test is not intended to be used as a donor screening test for HIV. The m-PIMA HIV-1/2 Detect test can be used as an aid in the diagnosis of HIV infection in pediatric and adult individuals, or as a supplementary assay when samples have already been tested using alternative methods (e.g. serological assays to screen for evidence of HIV infection). Assay description: Sample Handling and Processing According to the manufacturer “Peripheral blood may be collected from the patient either through standard finger or heel prick sampling techniques or venous blood draw. The sample volume required to run a test is 25μL. Finger or heel prick blood can be applied directly and immediately onto the m-PIMA HIV-1/2 Detect cartridge. When using EDTA anti-coagulated


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venous blood or plasma, the appropriate volume is transferred into the cartridge using a volumetric pipette or transfer capillary. Standard phlebotomy sample collection practices for obtaining both capillary and venous blood samples are to be followed. After applying the sample, the cartridge cap is snapped into place, eliminating the chance of sample spillage or contamination of the instrument. After closing the cap the cartridge is inserted into the m-PIMA Analyser and the test is initiated automatically. The steps described in the following subsections are performed automatically by the m-PIMA Analyser within the cartridge. RNA Isolation The RNA isolation consists of following steps:

a) Complete lysis of the sample based on chaotropic salts in order to release all nucleic acids including cell-associated HIV RNA and HIV RNA from plasma based particles.

b) Hybridization of oligonucleotides complementary to specific sequences of the HIV-1 and HIV-2 genome. These sequence specific capture oligonucleotides carry a 3’-terminal biotin-residue.

c) All biotinylated capture oligonucleotides are captured onto the surface of Streptavidin-Sepharose particles, thus any HIV RNA bound to a captured oligonucleotide is captured on the Sepharose too.

d) Washing of the Streptavidin-Sepharose particles to remove all contaminants that bind non-specifically to the particles, i.e. human nucleic acids, cellular and extracellular proteins, cell membrane fragments and low molecular weight molecules. After the washing steps, the remaining HIV RNA molecules are ready for reverse transcription (RT) followed by polymerase chain reaction (PCR).

Reverse Transcription and Amplification RNA which is captured onto the surface of the Streptavidin-Sepharose particles cannot be detected directly. Therefore, an amplification of HIV-specific nucleic acid sequences has to be performed. This is realized by PCR which allows an in vitro amplification of DNA sequences. Since most DNA polymerases do not synthesize DNA directly from RNA a reverse transcription of RNA into cDNA is necessary. Reverse transcription is an isothermal reaction which is performed at a defined temperature. The same reverse primers as for the subsequent PCR amplification are used for RT. The DNA primers hybridize with their complementary sequence onto the RNA and form a DNA-RNA hybrid. The reverse transcriptase then transcribes the RNA into its complementary cDNA by extending the oligonucleotide primer. The reverse transcription is followed by a denaturation step at a defined temperature in order to

• deactivate the reverse transcriptase • activate the DNA polymerase and • separate the RNA-DNA hybrid to make the newly formed cDNA accessible for primer

oligonucleotide binding and cyclic primer extension by PCR. Primers are short specific oligonucleotides that hybridize readily to their complementary


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sequences at the appropriate annealing temperature (annealing) and form the starting point for extension by a heat stable DNA polymerase. Primer annealing and the amplification of the DNA (elongation) by DNA polymerase are carried out at defined temperatures. The three steps (denaturation, annealing and elongation) describe one PCR cycle and are repeated 45 times. To facilitate simultaneous detection of more than one specific nucleic acid sequence a multiplex PCR is performed. Target amplification between HIV-1 group M/N and group O, and HIV-2 is facilitated by specific primer pairs. In addition, the primer pairs allow for the amplification of internal process controls. Detection Detection of PCR product is based on Competitive Reporter Monitored Amplification technology utilizing an array of immobilized oligonucleotide probes and complementary fluorescently labelled reporter oligonucleotides in solution. In order to maximize initial signal intensity, reporters used in this reaction have fluorescence labels at the 5’ and the 3’ ends. Under suitable conditions the reporter will specifically hybridize to the immobilized probes. The reporter oligonucleotides are also complementary to a specific sequence of a target amplicon that is generated during PCR that compete with the immobilized probes for binding of the reporter oligonucleotides. At the onset of the amplification reaction, none or a few target molecules are present and thus the reporter is free to bind to its complementary probe on the array. In the presence of target template more target amplicons with a reporter specific binding site are synthesized as the amplification reaction proceeds. As amplicons accumulate the hybridization kinetics become more dependent on the amplicon concentration. The more amplicons are synthesized the more reporter binds to them. In addition, the solid support to which the oligonucleotide probe is attached introduces a diffusion barrier which significantly reduces the hybridization rate. Thus, generally, solution phase reactions are kinetically favoured to solid phase reactions. Therefore the amount of reporter hybridized to the complementary probe decreases proportionally to the formation of new amplicons. This decrease is observed until a plateau in the amplification reaction is reached. Measuring the change in signal intensity of each probe can be achieved by imaging the fluorescence pattern on the array during the amplification process. Fluorescence images are collected during the annealing phase of each amplification cycle. After acquiring the hybridization pattern an algorithm is applied that is able to identify and eliminate different noise signals from the data obtained by the array assisted real-time PCR. The algorithm then calculates the cycle threshold values from the resulting amplification kinetics determining the presence of the analyte”.


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Product test kit contents:

m-PIMA HIV-1/2 Detect Cartridge Kit

10 x Cartridge Kit (product code 27011R010)

50 x Cartridge Kit (product code 27011R050)

Individually pouched test cartridges

10 50

Guide 1 1 Instrumentation:

Item Quantity Equipment: m-PIMA Analyser (product code 27030R001)

1 unit

Alternative Equipment Kits: m-PIMA Complete (product code 27030R002) containing product codes 27030R001, 27040R007, 27040R004, 260400059, 26040R009.

1x per kit component

Consumables required but not provided:

Item Quantity Finger Stick Sample Collection Kit (product code 260400199) Neonatal Sample Collection Kit (product code 270400200) Plastic Capillaries plain (product code 270400005) Plastic Capillaries EDTA-K2 (product code 270400006)

100 100 10 x 100 10 x 100

Items required but available separately:

Item Quantity USB Printer (product code 27040R007) 1 Power Drum (product code 27040R004) 1 Connectivity Pack IV (product code 260400059, compatible with software versions 0.26.01 and higher)

1

Printer Paper I (product code 26040R009) 10

Storage: The test kit should be stored at 4 ̶ 30 °C.


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Shelf-life upon manufacture: 9 months. Warnings/limitations: For warnings and limitations, please refer to current version of instructions for use.

Prioritization for prequalification Based on the established eligibility criteria, m-PIMA HIV-1/2 Detect was given priority for WHO prequalification assessment. Product dossier assessment Abbott Rapid Diagnostics Jena GmbH3 submitted a product dossier for m-PIMA HIV-1/2 Detect assay as per the “Instructions for compilation of a product dossier” (PQDx_018 v1). The information (data and documentation) submitted in the product dossier was reviewed by WHO staff and external technical experts (assessors) appointed by WHO. Notwithstanding, certain aspects of the product dossier submitted for stringent regulatory review for the purposes of CE marking were reviewed by a technical expert during the site inspection. Commitment: Manufacturer had a commitment of revision to the instructions for use as per WHO requirements and submission was due on December 2016. Version 09 of the product IFU, which reflects amendments agreed to as a commitment to prequalification, was provided to WHO October 2018. This commitment was met and closed. Based on the product dossier screening and assessment findings, the product dossier for m-PIMA HIV-1/2 Detect assay meets WHO prequalification requirements. Manufacturing site inspection

A comprehensive reinspection was performed at the site of manufacture (Loebstedter Str. 103-105, 07749 Jena, Germany) of m-PIMA HIV-1/2 Detect in 16 to 18 July 2018 as per the “Information for manufacturers on prequalification inspection procedures for the sites of manufacture of diagnostics” (PQDx_014). The inspection found that the manufacturer had

3 Manufacturer name and address changed from Alere Technologies GmbH to Abbott Rapid Diagnostics Jena GmbH, Orlaweg 1, D-07743 Jena, Germany.


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an acceptable quality management system and good manufacturing practices in place that ensured the consistent manufacture of a product of good quality.

The manufacturer's responses to the nonconformities found at the time of the inspection were accepted on 29 December 2018. Based on the site inspection and corrective action plan review, the quality management system for m-PIMA HIV-1/2 Detect meets WHO prequalification requirements. Product Performance evaluation

m-PIMA HIV-1/2 Detect assay is a qualitative nucleic acid amplification test for the detection of Human Immunodeficiency Virus (HIV) type 1 groups M/N and O and type 2 in human whole blood and plasma. This evaluation was performed on venous whole blood. A volume of 25µl of whole blood/specimen is needed to perform the assay. This type of assay does require laboratory equipment and can be performed in laboratories with limited facilities. Analytical evaluation The assay detected the following HIV-1 subtypes: A, B, C, D, F, AE, AG in whole blood. The total hit rate for 21 replicates (3 for each subtype) study was 100%. The limit of detection was estimated to be 2937 IU/ml [95% Fiducial limits: 2147 – 6079]; 1758.68 copies/mL [95% Fiducial Limits 1286 – 3640] using the WHO 3rd HIV-1 International Standard. No carry-over was detected. The repeatability assessment showed a hit rate of 100%, while the reproducibility hit rate was determined to be 100%. Clinical evaluation In this limited performance evaluation, on a panel of 301 infant whole blood specimens we found, in specimens from infants aged less than 18 months, an initial sensitivity of 98.67% (95% CI: 95.27-99.84) and an initial specificity of 100.00% (95% CI: 97.59-100.00) compared to the reference results (Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0) for all specimens tested. In specimens from individuals older than 15 years of age, we found an initial sensitivity of 90.00% (95% CI: 78.19-96.67) and an initial specificity of 100.00% (95% CI: 93.02-100.00). The final sensitivity and specificity for infant whole blood specimens were 99.33% (95% CI: 96.34-99.98) and 100.00% (95% CI: 97.59-100.00) respectively.


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In specimens from individuals older than 15 years of age, we found a final sensitivity of 94.00% (95% CI: 83.45-98.75) and a final specificity of 100.00% (95% CI: 93.02-100.00). In this study, the invalid rate was 5.58%.

Performance characteristics in comparison with an agreed reference standard Initial (95% CI) Final (95% CI) Sensitivity % Infant specimens: (N=150) Adult specimens: (N=50)

98.67% (95.27-99.84) 90.00% (78.19-96.67)

99.33% (96.34-99.98) 94.00% (83.45-98.75)

Specificity % Infant specimens: (N=151) Adult specimens: (N=51)

100.00% (97.59-100.00) 100.00% (93.02-100.00)

100% (97.59-100.0) 100.00% (93.02-100.00)

Invalid rate %

5.58%

Additional performance characteristics Subtype detection 21/21 were correctly classified Limit of detection using WHO 3rd International Reference Standard

2937 IU/ml [95% Fiducial limits: 2147 – 6079]; 1758.68 copies/mL [95% Fiducial Limits 1286 – 3640]

Carry-over 0%


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Key operational characteristics Validated specimen types

Venous (EDTA) and capillary whole blood. EDTA plasma.

Number of steps

4 steps

Time to result

0h:56 minutes (3 - 4 min hands-on time, 52 minutes on instrument)

Internal QC

Assay Process Controls 1- Internal process controls for HIV-1 and HIV-2 2- Positive hybridization control 3- Negative hybridization control

In-use stability of reagents

Reagents are all contained within the cartridge which is single use. Filled cartridges need to be processed immediately after sample loading.


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Labelling

1. Labels

2. Instructions for use


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1.0 Labels

Product labels Abbott Rapid Diagnostics Jena GmbH

page 1 of 10

1. m-PIMA HIV-1/2 Detect

Primary Packaging Label (Pouch Label)

Secondary Packaging and Labels for the 50x and the 50x Cartridge Kits


page 2 of 10


page 3 of 10

Secondary Packaging and Labels for the 10x Cartridge Kits


page 4 of 10


page 5 of 10

2. Consumables

2.1 Finger-Stick Sample Collection Kit

Packaging Label


page 6 of 10

2.2 Neonatal Sample Collection Kit

Packaging Labels


page 7 of 10

3. m-PIMA™ Analyser

Device Label

Packaging Label


page 8 of 10


page 9 of 10

4. Optional Items

4.1 USB Printer

Device Label

Packaging Label


page 10 of 10

4.2 Connectivity Pack

Connectivity Pack IV Box label


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2. Instructions for use4

4 English version of the IFU was the one that was assessed by WHO. It is the responsibility of the manufacturer to ensure correct translation into other languages

EN

m-PIMA™ HIV-1/2 DETECTCARTRIDGE GUIDE

0123

m-PIMA™ HIV-1/2 Detect2

EXPLANATION OF SYMBOLS

CE Mark

In vitro diagnostic medical device

Catalogue number

Batch code

Use by YYYY-MM-DD

Contains sufficient for < n > tests

Temperature limitation

Consult instructions for use

Do not reuse

Manufacturer

To keep dry

Attention symbol. Indicates special problems or important information. Read the accompanying text carefully.

30ºC4ºC

CARTRIDGE GUIDE 3

TABLE OF CONTENTS4 INTRODUCTION 4 Intended Use 4 Indications for Use 4 Intended User 5 Order Information and Scope of Delivery 5 Materials Required but Not Provided 5 Optional Items

5 TEST PRINCIPLE 5 Sample Handling and Processing 6 RNA Isolation 6 Reverse Transcription and Amplification 7 Detection

8 m-PIMA™ HIV-1/2 DETECT CARTRIDGE FEATURES 8 Cartridge Components 9 Quality Control (QC) Features 10 Reagents

11 WARNINGS AND PRECAUTIONS

14 m-PIMA™ HIV-1/2 DETECT TESTING PROCEDURE 14 Basic Workflow 15 How to discard used test cartridges 16 Finger Prick Sample Collection 17 Heel Prick Sample Collection 20 Venous Whole Blood Sample Collection 20 Sample Application via Transfer Capillaries 21 Test Report

23 LIMITATIONS 23 Interpretation of results 23 Matrix Effect 23 Sample Stability 24 Multiplex Testing

24 PERFORMANCE CHARACTERISTICS 25 Diagnostic sensitivity in HIV-1 fresh and frozen whole blood and plasma samples 26 Diagnostic sensitivity in HIV-2 samples 26 Diagnostic sensitivity and specificity in neonatal samples 26 Diagnostic sensitivity in seroconversion panels 27 Diagnostic specificity on frozen whole blood and plasma samples 28 Analytical sensitivity/ Limit of Detection 30 Analytical specificity 33 Genotype/subtype testing 35 Matrix effects 36 Multiplex assay 37 Carryover 37 Precision

37 TECHNICAL SUPPORT

38 REFERENCES


INTRODUCTIONVirological testing using assays specifically detecting HIV DNA or RNA already plays an important role in the diagnosis of HIV infection in newborns.(1) Early identification of HIV infection in exposed infants and referral for antiretroviral treatment leads to improved outcomes. Virological testing can also play a role in the confirmation of HIV infection in adults who have been tested positive with alternative methods (e.g. anti-HIV antibody/antigen tests). Currently, HIV virological testing is prohibitively expensive and complex, as it requires skilled technicians and regular equipment maintenance. m-PIMA™ HIV-1/2 Detect for the first time enables virological testing at the Point of Care performed by non-laboratory personnel in primary health setting.(2) Besides the conventional sample type, plasma, m-PIMA™ HIV-1/2 Detect is capable of processing whole blood, requiring only small volumes (25 μL) that can be easily obtained by finger or heel prick (for neonates) sampling techniques. Using whole blood as a sample instead of plasma also takes advantage of the well documented fact that HIV-particles adhere to various types of blood cells like platelets (3-6) and monocytes,(7) but also to CD4-/CD8- T cells, probably originating from infected CD4+ T cells.(8) HIV RNA and HIV antigen were also found to be associated with erythrocytes.(9-11) In addition, intracellular HIV RNA is produced within infected lymphocytes circulating in the peripheral blood.(12-20) By using whole blood, cell-associated viral particles are included into the analysis thus providing a higher probability to detect a HIV infection.(21)

Intended Use The m-PIMA™ HIV-1/2 Detect test is a qualitative nucleic acid amplification test for the detection of Human Immunodeficiency Virus (HIV) type 1 groups M/N and O, and type 2 RNA in human whole blood and plasma samples. The test can be used in laboratory as well as non-laboratory environments. The m-PIMA™ HIV-1/2 Detect test is intended for in vitro diagnostic use. The m-PIMA™ HIV-1/2 Detect test is not intended to be used as a donor screening test for HIV.

Indications for UseThe m-PIMA™ HIV-1/2 Detect test can be used as an aid in the diagnosis of HIV infection in pediatric and adult individuals, or as a supplementary assay when samples have already been tested using alternative methods (e.g. serological assays to screen for evidence of HIV infection).

Intended UserThe m-PIMA™ HIV-1/2 Detect test is intended to be used by trained health care or laboratory professionals or other health care workers receiving appropriate training. The test is suitable for laboratory and non-laboratory environments and for near-patient testing.

CARTRIDGE GUIDE 5

Order Information and Scope of Deliverym-PIMA™ HIV-1/2 Detect 50x Cartridge Kit (catalogue no. 27011R050):• 50 individually pouched test cartridges• 1 m-PIMA™ HIV-1/2 Detect Cartridge Guide

m-PIMA™ HIV-1/2 Detect 10x Cartridge Kit (catalogue no. 27011R010):• 10 individually pouched test cartridges• 1 m-PIMA™ HIV-1/2 Detect Cartridge Guide

Materials Required but Not Providedm-PIMA™ Analyser (catalogue no. 27030R001) with installed software version 0.26.1 or higher.

Optional ItemsFinger Stick Sample Collection Kit (100) (catalogue no. 260400199) Neonatal Sample Collection Kit (100) (catalogue no. 270400200) Plastic Capillaries plain (catalogue no. 270400005) Plastic Capillaries EDTA-K2 (catalogue no. 270400006)

Before performing a m-PIMA™ HIV-1/2 Detect test, please refer to these instructions for detailed information on the test procedure.

TEST PRINCIPLE

Sample Handling and Processing Peripheral blood may be collected from the patient either through finger or heel prick sampling techniques or venous blood draw (draw as described on pages 16 - 20). The sample volume required to run a test is 25 μL. Finger or heel prick blood can be applied directly and immediately onto the m-PIMA™ HIV-1/2 Detect cartridge. When using EDTA anti-coagulated venous blood or plasma, the appropriate volume is transferred into the cartridge using a volumetric pipette or transfer capillary (please refer to page 12 for allowed anti-coagulants). Standard phlebotomy sample collection practices for obtaining both capillary and venous blood samples are to be followed. After applying the sample, the cartridge cap is snapped into place, eliminating the chance of sample spillage or contamination of the instrument. After closing the cap the cartridge is inserted into the m-PIMA™ Analyser and the test is initiated automatically. The steps described in the following subsections are performed automatically by the m-PIMA™ Analyser within the cartridge.


RNA IsolationThe RNA isolation consists of following steps:

a Complete lysis of the sample based on chaotropic salts in order to release all nucleic acids including cell-associated HIV RNA and HIV RNA from plasma based particles.

b Hybridization of oligonucleotides complementary to specific sequences of the HIV-1 and HIV-2 genome. These sequence specific capture oligonucleotides carry a 3’-terminal biotin-residue.

c All biotinylated capture oligonucleotides are captured onto the surface of Streptavidin-Sepharose particles, thus any HIV RNA bound to a captured oligonucleotide is captured on the Sepharose too.

d Washing of the Streptavidin-Sepharose particles to remove all contaminants that bind non-specifically to the particles, i.e. human nucleic acids, cellular and extracellular proteins, cell membrane fragments and low molecular weight molecules.

After the washing steps, the remaining HIV RNA molecules are ready for reverse transcription (RT) followed by polymerase chain reaction (PCR).

Reverse Transcription and Amplification RNA which is captured onto the surface of the Streptavidin-Sepharose particles cannot be detected directly. Therefore an amplification of HIV-specific nucleic acid sequences has to be performed. This is realized by PCR which allows an in vitro amplification of DNA sequences. Since most DNA polymerases do not synthesize DNA directly from RNA a reverse transcription of RNA into cDNA is necessary. Reverse transcription is an isothermal reaction which is performed at a defined temperature. The same reverse primers as for the subsequent PCR amplification are used for RT. The DNA primers hybridize with their complementary sequence onto the RNA and form a DNA-RNA hybrid. The reverse transcriptase then transcribes the RNA into its complementary cDNA by extending the oligonucleotide primer. The reverse transcription is followed by a denaturation step at a defined temperature in order to

• deactivate the reverse transcriptase

• activate the DNA polymerase and

• separate the RNA-DNA hybrid to make the newly formed cDNA accessible for primer oligonucleotide binding and cyclic primer extension by PCR.

CARTRIDGE GUIDE 7

Primer are short specific oligonucleotides that hybridize readily to their complementary sequences at the appropriate annealing temperature (annealing) and form the starting point for extension by a heat stable DNA polymerase. Primer annealing and the amplification of the DNA (elongation) by DNA polymerase are carried out at defined temperatures. The three steps (denaturation, annealing and elongation) describe one PCR cycle and are repeated 45 times. To facilitate simultaneous detection of more than one specific nucleic acid sequence a multiplex PCR is performed. Target amplification between HIV-1 group M/N and group O, and HIV-2 is facilitated by specific primer pairs. In addition the primer pairs allow for the amplification of internal process controls.

DetectionDetection of PCR product is based on Competitive Reporter Monitored Amplification technology utilizing an array of immobilized oligonucleotide probes and complementary fluorescently labeled reporter oligonucleotides in solution.(22) In order to maximize initial signal intensity, reporters used in this reaction have fluorescence labels at the 5’ and the 3’ ends. Under suitable conditions the reporter will specifically hybridize to the immobilized probes. The reporter oligonucleotides are also complementary to a specific sequence of a target amplicon that is generated during PCR that compete with the immobilized probes for binding of the reporter oligonucleotides. At the onset of the amplification reaction, none or a few target molecules are present and thus the reporter is free to bind to its complementary probe on the array. In the presence of target template more target amplicons with a reporter specific binding site are synthesized as the amplification reaction proceeds. As amplicons accumulate the hybridization kinetics become more dependent on the amplicon concentration. The more amplicons are synthesized the more reporter binds to them. In addition, the solid support to which the oligonucleotide probe is attached introduces a diffusion barrier which significantly reduces the hybridization rate. Thus, generally, solution phase reactions are kinetically favoured to solid phase reactions.(23) Therefore the amount of reporter hybridized to the complementary probe decreases proportionally to the formation of new amplicons. This decrease is observed until a plateau in the amplification reaction is reached. Measuring the change in signal intensity of each probe can be achieved by imaging the fluorescence pattern on the array during the amplification process. Fluorescence images are collected during the annealing phase of each amplification cycle. After acquiring the hybridization pattern an algorithm is applied that is able to identify and eliminate different noise signals from the data obtained by the array assisted real-time PCR. The algorithm then calculates the cycle threshold values from the resulting amplification kinetics determining the presence of the analyte.


m-PIMA™ HIV-1/2 DETECT CARTRIDGE FEATURESCartridge Components The m-PIMA™ HIV-1/2 Detect test cartridge consists of a black solid cartridge base, with an attached cartridge cap that is secured in place after sample collection is completed. Sufficient sample loading can be controlled by the operator via a control window. The cartridge also consists of several internal compartments containing dry reagents and an on board buffer reservoir. The compartments of the cartridge are connected through a micro-fluidic network and air/liquid movement within the cartridge is regulated by the m-PIMA™ Analyser through valves within the cartridge. The RT-PCR reaction takes place within the reactor chamber of the cartridge. All liquid waste produced during the test is sealed within the cartridge. The cartridge is a completely sealed system once the cap is closed. Air pressure for moving the liquids into the different compartments is applied via a septum. The septum is pricked by a needle connected to the pneumatic module of the m-PIMA™ Analyser. Several built-in safety features prevent template contamination (filter, sealed waste container). Risks regarding PCR template contamination of samples, instrument, cartridge or the environment are minimized as the test is designed to capture un-spliced RNA whereas amplicons generated in the test process represent short targets downstream of the capture binding sites.

Sample Capillary Air Channel Reactor Chamber

Buffer Reservoir Control Window Cartridge Cap

m-PIMA™ HIV-1/2 Detect

CARTRIDGE GUIDE 9

Quality Control (QC) Features Data Matrix Code (DMC) The DMC printed on the cartridge label contains cartridge specific information including cartridge and lot identifier, the expiry date and the assay ID. Upon insertion of the test cartridge the m-PIMA™ Analyser automatically reads the DMC. After successful reading of the DMC, the test will commence. In case of an expired cartridge, an illegible DMC or lack of matching software to perform the encoded assay, an error message will be displayed by the m-PIMA™ Analyser and the test will not start.

Sample Detection Control The sample volume processed during a test is defined by the dimensions of the sample capillary. The nominal volume held by the capillary is 25 (± 2) µL. The test cartridge also contains a sample control window, allowing the operator to control for sample loading. At the start of every test run the m-PIMA™ Analyser checks whether sample has been loaded into the m-PIMA™ HIV-1/2 Detect cartridge via the sample control window. If insufficient sample has been loaded into the test cartridge the analysis will not start and an error message is displayed. In order to allow sample presence detection of colorless sample such as plasma, a dye is applied onto the inner surface of the sample capillary. The dye mixes with the sample upon contact and allows sample detection.

Assay Process Controls Each test cartridge has built in process controls ensuring for proper function of the assay.

• Internal process controls for both HIV-1 and HIV-2 are deposited in the lysis chamber of the cartridge. These controls run together with the patient sample through all assay processing steps and enable for detection of potential failures during lysis, RNA isolation, capturing, PCR and detection. Sequences of these positive controls are designed to hybridize to the same capture oligonucleotides and primers as the respective targets and will be distinguished during detection by specific reporters and probes on the micro array.

• The positive hybridization control is made of probes on the array that are complementary to specific reporters in solution. The positive hybridization control does not interfere with PCR-primers in the RT-PCR mix and therefore has to produce a valid signal above a defined threshold while it must not produce a ct value (detects if hybridization conditions are out of range).

• The negative hybridization control is made of probes on the micro array not being complementary to any reporter. The hybridization signal for this control has to be lower than a defined threshold (detects non-specific hybridization). The m-PIMA™ HIV-1/2 Detect also considers multiple QC parameters to ensure proper function of the m-PIMA™ Analyser and consistency of raw data for data analysis.


Reagents

% (w/w)

Sample Capillary (coated with) K3EDTA*2H2O Brilliant Black

65 %

Lysis Mixture (tablet, embedded in cartridge) Guanidin-HCl N-Lauroylsarcosine Na4EDTA*4H2O Na2EDTA*2H2O Antifoam BC 2527

89.7 % 0.92 % 1.23 %

Proteinase K Tablet (tablet, embedded in cartridge) Proteinase K

Capture-oligonucleotides/internal process controls (on solid support, embedded in cartridge) Oligonucleotides with biotin residues Tris-HCl Na2EDTA*2H2O Tris MgCl2 NaCl BSA, acetylated artificial virus RNA

RT-PCR Mixture 1 (pellet, embedded in cartridge) anti-Taq-antibody Taq polymerase Reverse Transcriptase Tris-HCl dNTP (dATP, dCTP, dGTP, dTTP) mix RNase Inhibitor

RT-PCR Mixture 2 (pellet, embedded in cartridge) Oligonucleotides Oligonucleotides with Cy5 residues Tris-HCl Na2EDTA*2H2O

Streptavidin-Sepharose (solid particles, embedded in cartridge) Streptavidin-Sepharose

Washing Mixture (tablet, embedded in cartridge) Guanidin-HCl Na4EDTA*4H2O Na2EDTA*2H2O

93.3 %

1.2 %

Buffer A (liquid, sealed in cartridge) NaN3 Guanidin-HCl Na4EDTA * 4H2O Na2EDTA * 2H2O Triton X-100 Tween 20 KCl Tris MgCl2 ultrapure water

0.04 % 0.32 %

0.005 %

CARTRIDGE GUIDE 11

WARNINGS AND PRECAUTIONSIn Vitro Diagnostic Use

For in vitro diagnostic use.

The m-PIMA™ HIV-1/2 Detect test is not intended to be used as a donor screening test for HIV.

m-PIMA™ HIV-1/2 Detect cartridges are intended to be used only in connection with the m-PIMA™ Analyser.

The use of the m-PIMA™ HIV-1/2 Detect cartridge is limited to personnel trained to perform the assay.

m-PIMA™ HIV-1/2 Detect cartridges are for single use only.

Safety Precautions

Follow proper infection control guidelines for handling all blood specimens and related items.

Always wear powder free gloves when handling or collecting specimens or test cartridges, and change gloves after each sample collection and before handling a new cartridge (please see pages 14 and 15 for details).

DO NOT pipette by mouth.

DO NOT eat, drink, smoke, apply cosmetics or handle contact lenses in areas where samples are handled.

Clean and disinfect spills of specimens by including the use of a disinfectant such as 1.0 % sodium hypochlorite or other suitable disinfectant.

Decontaminate and dispose of all potentially infectious materials in accordance with local, state and federal regulations.

Material Safety Data Sheet for this product is available on request through Technical Support.


Handling Precautions

Only use m-PIMA™ HIV-1/2 Detect test cartridges at ambient temperatures of 10 - 40 °C and relative humidity below 90 %.

Only use venous EDTA whole blood or plasma and capillary whole blood (from the finger or heel) with the m-PIMA™ HIV-1/2 Detect test. The use of other sample types was not evaluated and is NOT recommended as they may result in inaccurate or invalid results. DO NOT use clotted blood samples since they may lead to invalid or inaccurate test result.

When using heel prick samples make sure that the pricking site is clean and not contaminated with maternal blood.

Cartridges are supplied with the cap attached to the cartridge. DO NOT close the cap until the cartridge is fully loaded with sample since this can lead to an invalid test result.

DO NOT attempt to re-open a closed cap. Damaged caps can lead to incomplete cartridge closure and an invalid test result.

DO NOT touch the transparent foil cover of the reactor chamber. Damaged or soiled covers can lead to an invalid test result.

DO NOT use cartridges that are damaged, that have become wet or if the foil pouch has been damaged since reagent integrity might be compromised.

Contamination and Inhibition

The following precautions should be observed to minimize the risks of RNase contamination, cross-contamination between samples, and inhibition:

Always wear powder free gloves when handling or collecting specimens or test cartridges, and change gloves after each sample collection and before handling a new cartridge (please see pages 14 and 15 for details).

When using a volumetric pipette, always use aerosol barrier pipette tips to prevent sample-to-sample contamination. If no aerosol barrier pipette tips are available use single use transfer capillaries. NEVER re-use pipette tips or transfer capillaries

During collection, handling and application of samples, compliance with good laboratory practices is essential to minimize the risk of cross-contamination between samples, and the inadvertent introduction of ribonucleases (RNases) into samples.

Proper aseptic technique should always be used when working with RNA.

Amplification technologies such as PCR are sensitive to accidental introduction of product from previous amplification reactions.

CARTRIDGE GUIDE 13

Incorrect results could occur if either the clinical specimen or sample capillary of the cartridge become contaminated by accidental introduction of even a few molecules of amplification product.

Storage Instructions

Store cartridges at ambient temperature (4 - 30 °C). The surrounding temperature may lie outside this range for a limited period of time (i.e. up to 48 hours at 2 °C and up to 72 hours at 40 °C). Once removed from their protective pouch, cartridges are stable for up to 10 minutes at 40 °C and 90 % relative humidity. DO NOT freeze the test cartridges.

Indication of Instability or Deterioration

When a positive or negative control value is out of the expected range, it may indicate deterioration of the assay reagents. Associated test results are invalid and samples must be retested.


m-PIMA™ HIV-1/2 DETECT TESTING PROCEDUREBasic Workflow 1. Switch on the m-PIMA™ Analyser and wait for the initialization to be completed.

The presence of the «HOME» screen indicates the analyzer is ready for use.

2. Always wear a new pair of gloves for every cartridge! Remove a m-PIMA™ HIV-1/2 Detect cartridge from its pouch and completely flip open the cartridge cap to fully expose the sample capillary. Only open the foil pouch when ready to load sample on the cartridge.

3. Apply sample onto the m-PIMA™ HIV-1/2 Detect cartridge. Enough sample is applied when the sample control window is filled with blood.

4. Once sample loading is completed, close the cartridge by capping the capillary with the cartridge cap as shown in the images 11 - 14 on page 19. Do not insert the cartridge into the device before ensuring that the cap is securely in place.

5. Filled cartridges need to be processed immediately after sample loading.

6. Press «RUN TEST» on the m-PIMA™ Analyser and insert the test cartridge in the direction indicated by the arrow on the cartridge label. Follow on-screen instruction or refer to the m-PIMA™ Analyser User Guide for details on how to proceed with the analysis.

7. Remove the cartridge when prompted by the m-PIMA™ Analyser (step 1). Always wear gloves when removing a cartridge from the instrument! The test result is displayed on the instrument screen.

8. To discard of used test cartridges, preferably seal them within the gloves (the following example is referring to right-handed users):

• Hold the test cartridge in your left hand. With your right hand, pinch the glove of your left hand at wrist level and pull it down above the cartridge and off your fingers (step 2 and 3). Hold glove with sealed cartridge in your right hand fist.

• Insert one or two fingers of your left ungloved hand under the inside rim on the palm side of the right glove; push glove inside out and down onto the fingers and over the left glove and cartridge (step 4).

• Grasp the gloves, which are now together and inside out sealing the cartridge, with your left hand and remove from your right hand (step 5).

• Discard as biohazard waste (step 6).

CARTRIDGE GUIDE 15

m-PIMA

1 2

3 4

5 6

How to discard used test cartridges(Please find a detailed description on previous page.)


Finger Prick Sample Collection (26)

1. Always wear a new pair of gloves for every patient! Prepare patient for finger prick sample collection. The best locations for finger pricks are the 3rd and 4th fingers. Do not use the tip of the finger or the center of the finger pad. Avoid the side of the finger where there is less soft tissue, where vessels and nerves are located, and where the bone is closer to the surface. The 2nd (index) finger tends to have thicker, callused skin. The fifth finger tends to have less soft tissue overlying the bone. Avoid puncturing a finger that is cold, cyanotic, swollen, scarred or covered with a rash. Avoid fingers with rings on.

2. Warm fingers if needed. Have the patient hold their hand downwards to increase the blood flow to the finger. Note: The patient should always sit higher than the person performing the finger prick.

3. Wipe the tip of the appropriately selected finger with an alcohol swab and let the alcohol air dry.

4. If the cartridge is filled directly from the pricked finger, continue with step 5. If a transfer capillary is used, please refer to the section on sample application via transfer capillary (page 20).

5. Remove one m-PIMA™ HIV-1/2 Detect cartridge from its foil pouch and open the plastic cap to fully expose the sample capillary.

6. Use a sterile lancet to make a skin puncture just off the center of the finger pad. To obtain a representative blood sample constant blood flow is of utmost importance.

When using an automated lancet it is essential to press the lancet firmly onto the finger and maintain contact while ejecting the lancet. Do not squeeze or apply strong repetitive pressure (milking) to the site; this may result in tissue-fluid contamination of the specimen. If necessary, gentle massaging of the finger may be conducted in order to ensure a steady blood flow.

7. Wipe off the first drops of blood with a dry gauze swab. Ensure steady blood flow that generates large enough drops of blood. If necessary, wipe off another drop, until the blood flows freely.

8. Allow blood to flow freely from the pricked finger directly into the sample capillary by holding the cartridge at a 45 degree angle for sample loading. Wait until the sample capillary is completely filled with blood. Enough sample is applied when the sample control window is filled with blood. Then remove the cartridge from the finger and let the patient apply direct pressure to the wound side with a clean dry swab.

9. Continue with step 4 of the Basic Workflow description (page 14).

10. Apply a band aid to the patient’s finger.

CARTRIDGE GUIDE 17

Heel Prick Sample Collection (24, 25)

Selection of a site for capillary sampling in a pediatric patient is usually based on the age and weight of the patient. If the child is walking, the child’s feet may have calluses that hinder adequate blood flow. Children older than 6 months and a body weight greater than 10 kg may be more suitable for finger prick sample collection. Please refer to your institutional standard operating procedures in this regard.

1. It is recommended to comfort the baby. Ask the parent to assist. Ensure the baby is cuddled and in a secure position for taking the sample.

2. Ensure the baby is warm and comfortable. Additional warming of the foot is not required.

3. Always wear a new pair of gloves for every patient! Clean the pricking site of the heel. The heel should be completely dry before taking the sample.

4. If the cartridge is filled directly from the pricked heel, continue with step 5. If a transfer capillary is used, please refer to the section on sample application via transfer capillary (page 20).

5. Remove one m-PIMA™ HIV-1/2 Detect cartridge from its foil pouch and open the plastic cap to fully expose the sample capillary.

6. Use a sterile lancet appropriate for neonates to make a skin puncture. The external and internal limits of the calcaneus are the preferred pricking sites (hatched areas in image 3 on page 18). To obtain a representative blood sample constant blood flow is of utmost importance. When using an automated lancet it is essential to press the lancet firmly onto the heel and maintain contact while ejecting the lancet. Do not squeeze or apply strong repetitive pressure (milking) to the site; this may result in tissue-fluid contamination of the specimen. If necessary, gentle massaging of the heel may be conducted in order to ensure a steady blood flow.

7. Wipe off the first drops of blood with a dry gauze swab. Ensure steady blood flow that generates large enough drops of blood. If necessary, wipe off another drop, until the blood flows freely.

8. Allow blood to flow freely from the pricked heel directly into the sample capillary by holding the cartridge at a 45 degree angle for sample loading. Wait until the sample capillary is completely filled with blood. Enough sample is applied when the sample control window is filled with blood. Then remove the cartridge from the heel and let the parent apply direct pressure to the wound side with a clean dry swab.

9. Continue with step 4 of the Basic Workflow description (page 14).

10. Apply a band aid to the infant’s heel.


LOT

REF

m-PIMA

1 2

3 4

5 6

7 8

CARTRIDGE GUIDE 19

m-PIMA™ HIV-1/2 DetectHIV-1/2

m-PIMA™ HIV

9 10

11 12

13 14

15 16


Venous Whole Blood Sample Collection (27)

1. Always wear a new pair of gloves for every patient or every sample you handle! Collect blood aseptically by venipuncture into a sterile EDTA (ethylenediaminetetraacetic acid) blood collection tube.

2. Invert collection tube 8 - 10 times.

3. Store at ambient temperature (18 - 28 °C). The sample must be analyzed within 24 hours of draw. If samples need to be stored for longer periods, please refer to the section on Sample Stability (page 23) for detailed information.

4. Before using sample for testing, invert collection tube 10 - 15 times to ensure proper sample mixing.

5. If plasma needs to be tested, collection tubes should be centrifuged at 800 - 1600 x g for 20 minutes at ambient temperature.

6. If the cartridge is filled with a volumetric pipette, continue with step 7. If a transfer capillary is used, please refer to the section on sample application via transfer capillary (see below).

7. When using a volumetric pipette, always use aerosol barrier pipette tips to avoid sample-to-sample contamination. If no aerosol barrier pipette tips are available use single use transfer capillaries. NEVER re-use pipette tips.

8. Apply 25 µL into the sample capillary of the m-PIMA™ HIV-1/2 Detect cartridge and continue with step 4 of the Basic Workflow description (page 14).

Sample Application via Transfer Capillaries

Transfer Capillaries can be used to apply all sample types compatible with m-PIMA™ HIV-1/2 Detect. For samples containing EDTA, use capillaries without additional anticoagulant. For blood collected directly from a pricked finger or heel, always use capillaries containing EDTA (please refer to page 5 for information regarding available capillary options).Always use a new transfer capillary for every patient!

1. When collecting whole blood directly from a pricked finger or heel, put one end of the EDTA capillary in contact with the blood drop. Hold the capillary almost horizontally. When collecting venous whole blood/plasma, insert a plain capillary into the collection tube and hold them both almost horizontally, without spilling the sample.

2. Allow the capillary to fill approximately half way without trapping air bubbles.

3. Close the opposite end of the transfer capillary with your finger to prevent unwanted release of the sample.

CARTRIDGE GUIDE 21

4. Put the open end of the transfer capillary in contact with the sample capillary of the test cartridge and hold the transfer capillary almost vertically. Remove the finger from the other end. The sample capillary will automatically draw blood from the transfer capillary. Observe the descent in fill level of the transfer capillary. It will stop when enough sample is transferred to the cartridge.

5. Dispose of the transfer capillary as potentially infectious materials in accordance with local, state and federal regulations and continue with step 4 of the Basic Workflow description (page 14).

Test Report Test Reports are stored in the onboard archive of the m-PIMA™ Analyser. Reports contain the following information: Test name, sample ID, qualitative test results for HIV-1 M/N and O and HIV-2, result number, date and time of test, cartridge ID (incl. lot information), operator ID, device serial number, software version, instrument, assay process and data analysis QC information. Test results can be either exported, transmitted to a remote server using Connectivity Packs or printed using the USB Printer available as accessories to the m-PIMA™ Analyser.

Test Result A qualitative result (detected/ not detected) is provided for analytes HIV-1 (groups M/N and O) and HIV-2. If for one or more of the simultaneously measured analytes (HIV-1 M/N, HIV-1 O and HIV-2) an „HIV detected (positive)“ result is displayed then HIV RNA is detected and the sample is HIV positive. If an “HIV not detected” result is displayed on the test report for all of the three simultaneously measured analytes (HIV-1 M/N, HIV-1 O and HIV-2), then no HIV RNA is detected in the sample (see examples for printed test reports on page 22).


Test Result Reporting (examples)

Test Report for HIV positive results Test Report readout if no HIV is detected

Note: The indicated test result summary lines “HIV detected (positive)” and “HIV not detected” have been introduced with m-PIMA™ Analyser software version 0.26.3. Previous software versions display individual analyte test results only.

QC Parameters Sample Detection: control for presence of sample

Device: multiple QC parameters for the functionality of the m-PIMA™ Analyser

HIV-1 Positive Control: internal process control for HIV-1

HIV-2 Positive Control: internal process control for HIV-2

Negative Control: control for non-specific hybridization

Analysis: multiple QC parameters for the analysis process, incl. positive hybridization control

Test Report

m-PIMA HIV-1/2 Detect

Sample ID2347-SRT-2019

HIV not detected

Result No. 34

Date / Time 2019-08-12 11:50Cartridge IDOperatorDevice SerialSoftwareQC

Sample DetectionDeviceHIV-1 Positive ControlHIV-2 Positive ControlNegative ControlAnalysis

Signature

0123456554OP-23

NAT-040001098

0.26.3

PassPassPassPassPassPass

HIV-1 M/NHIV-1 OHIV-2

Not detectedNot detectedNot detected

Test Report

m-PIMA HIV-1/2 Detect

Sample ID23-07-2019-ABC

HIV detected (positive)

Result No. 107



Signature

0123456789SAM MILLER

NAT-04000935

0.26.3


HIV-1 M/NHIV-1 OHIV-2

DetectedNot detectedNot detected

CARTRIDGE GUIDE 23

LIMITATIONSInterpretation of results Specimens “Not detected” for HIV-1 or HIV-2 RNA by m-PIMA™ HIV-1/2 Detect do not necessarily indicate the absence of an HIV infection in the respective patient. As with any diagnostic test, results from m-PIMA™ HIV-1/2 Detect need be interpreted in conjunction with other clinical and laboratory findings. Though rare, mutations within the highly conserved region of the viral genome covered by the primers and/or probes used for m-PIMA™ HIV-1/2 Detect may result in the failure to detect the virus.(28, 29) Detection of HIV-1 and HIV-2 RNA is dependent on the number of virus particles present in the specimen and may be affected by specimen collection methods and patient factors (e.g., age, presence of symptoms, stage of the infection and viral setpoint). Patients receiving antiretroviral therapy (ART) or preventive therapy (e.g. PrEP, PEP, etc) may have undetectable levels of HIV RNA despite the presence of an HIV infection. m-PIMA™ HIV-1/2 Detect is not intended for confirmation of an HIV infection in patients receiving ART or preventive therapy.

Matrix Effect Due to the inclusion of cell-associated HIV RNA into the analysis, the number of virus particles per given sample volume is higher in whole blood samples than in plasma samples. Samples of 186 patients from Cohort B (see below) with corresponding plasma viral loads between 0 and 2491 cp/mL (Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0) were analyzed. While the diagnostic sensitivity (95 % confidence interval) with Roche Cobas® using 1 mL plasma was 48.4 % [41.0 %, 55.8 %], the sensitivities with m-PIMA™ HIV-1/2 Detect using a sample volume of 25 µL was 51.4 % [43.8 %, 59.0 %] for capillary blood and 56.6 % [49.1 %, 63.9 %] for venous whole blood, but only 2.7 % [0.9 %, 6.2 %] for the corresponding plasma samples, respectively, indicating a loss of sensitivity for low viral load samples when using plasma instead of whole blood.

Sample Stability Venous whole blood, collected into EDTA tubes, can be stored at ambient temperature (18 – 28 °C) for up to 24 hours after draw before testing with m-PIMA™ HIV-1/2 Detect. If testing is not possible within 24 hours, samples should be aliquoted and frozen at least at -80 °C either as whole blood or plasma within 24 hours after draw. Frozen samples should be thawed at ambient temperature and, once thawed, tested immediately. It is recommended to invert the thawed sample tubes 10 - 15 times before pipetting.

Note: Sample storage at ambient temperatures for more than 24 hours, or at temperatures exceeding 28 °C, or more than one freeze thaw cycle may negatively impact test performance, especially in samples with viral loads < 4000 cp/mL.


Multiplex Testing Multiplex testing refers to the simultaneous presence of HIV-1 M/N, HIV-1 O and/or HIV-2 in the same patient sample. The capability of multiplex testing is potentially affected by viral load ratios that exceed the ones which were tested by Alere Technologies GmbH. In case of larger viral load differences, the ability to detect the analyte present in lower concentration may be reduced.

PERFORMANCE CHARACTERISTICSPerformance characteristics of the m-PIMA™ HIV-1/2 Detect test were established by testing at Alere Technologies GmbH in Jena, Germany, and at external sites in Mozambique, Uganda, the United States of America and Germany. Samples from several African and European cohorts were tested. Due to the limited availability of samples containing HIV-1 group O and HIV-2, the majority of samples included in these studies were positive for HIV-1 group M/N only.

Cohort A: A total of 254 matched pairs of frozen venous EDTA whole blood and plasma samples from treatment naïve HIV-1 positive donors after seroconversion were collected at clinical sites in Germany and tested at Alere Technologies GmbH. For each plasma sample HIV-1 viral load data from Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0 was available.

Cohort B: Fresh venous and finger prick whole blood from 200 HIV-1 positive donors after seroconversion (91.5 % on ART) tested at clinical sites in Germany. Matching plasma samples were tested at Alere Technologies GmbH. For each plasma sample HIV-1 viral load data from Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0 was available.

Cohort C: Fresh finger prick whole blood from 200 HIV-1 positive donors after seroconversion (73.5 % on ART) tested at a clinical site in Uganda. Matching venous whole blood samples were tested at the Uganda Virus Research Institute. For each sample HIV-1 plasma viral load data from Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0 was available.

Cohort D: Frozen EDTA plasma samples from 101 HIV-2 positive donors after seroconversion (72 % on ART) collected at clinical sites in several African countries and tested at the University of Washington (UW), USA. For each plasma sample HIV-2 viral load data from a HIV-2 laboratory defined assay, developed at UW, utilizing the Abbott m2000 platform, was available.(30)

CARTRIDGE GUIDE 25

Cohort E: Fresh heel prick whole blood samples from 223 children (median age 1 month; range: 1 - 11) born to HIV infected mothers tested at clinical sites in Mozambique. For each whole blood sample positivity for HIV-1 was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Qualitative test.

Cohort F: Venous EDTA Plasma samples obtained from individuals during HIV-1 antibody seroconversion. Ten commercially available panels including 128 samples of early seroconversion were purchased from Helvetica Health Care, Geneva, Switzerland and tested at Alere Technologies GmbH. For each plasma sample positivity for HIV-1 was determined using the Abbott ARCHITECT® HIV Ag/Ab Combo.

Cohort G: A total of 1203 frozen venous EDTA whole blood and plasma samples from presumably healthy European donors (commercially available through BBI Solutions, Cardiff, UK) were tested at Alere Technologies GmbH. The clinical samples have been tested negative for HIV-1/2 antibodies, HIV-1 NAT, HBV NAT, Hepatitis B Surface antigen, HCV NAT, Hepatitis C virus antibodies and Syphilis.

Cohort H: Fresh venous EDTA whole blood and plasma samples from presumably healthy European donors (commercially available through the Institut für Transfusionsmedizin der Friedrich Schiller Universität Jena, Germany) were tested negative for HIV-1/2 antibodies, HCV antibodies, Hepatitis B Surface Antigen, Hepatitis B Core-Protein antibodies, Syphilis, irregular antibodies, HCV NAT and HIV-1 NAT (Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0).

Diagnostic sensitivity in HIV-1 fresh and frozen whole blood and plasma samples Diagnostic sensitivity of a test is defined as the proportion of subjects with the clinical condition of interest who have a positive test result and is expressed as a proportion or percentage. Diagnostic sensitivity was determined using a total of 295 venous whole blood samples, 235 plasma samples and 74 capillary blood samples from cohorts A, B and C with corresponding plasma viral loads above the limit of detection of m-PIMA™ HIV-1/2 Detect (≥ 2491 cp/mL determined with Roche Cobas®). The observed diagnostic sensitivity [95 % confidence intervals] of m-PIMA™ HIV-1/2 Detect for HIV-1 in venous whole blood, plasma and capillary whole blood samples was 98.98 % (292/295) [97.06 %, 99.79 %], 99.57 % (234/235) [97.65 %, 99.99 %] and 98.65 % (73/74) [92.70 %, 99.97 %], respectively. No samples reactive for HIV-2 were found in these cohorts.


Diagnostic sensitivity in HIV-2 samples Diagnostic sensitivity was determined using a total of 37 plasma samples from cohort D with corresponding plasma viral loads above the limit of detection of m-PIMA™ HIV-1/2 Detect (≥ 952 cp/mL, equivalent to ≥ 98 cp/mL determined with Abbott m2000). The observed diagnostic sensitivity [95 % confidence intervals] of m-PIMA™ HIV-1/2 Detect for HIV-2 in plasma samples was 97.30 % (36/37) [85.84 %, 99.93 %]. Of the 101 patients in cohort D, 8 were co-infected with HIV-1 and HIV-2 according to historical serological test data. Of these, 4 patients showed detectable viral load for one or both of the virus types on m-PIMA™ HIV-1/2 Detect. No discrepant results were observed for HIV-2. One of the patients reactive for HIV-1 on Abbott m2000 was undetected on the m-PIMA™ HIV-1/2 Detect, but the viral load for this sample was below the limit of detection of the m-PIMA™ HIV-1/2 Detect. The other 4 patients had undetectable virus with both m-PIMA™ HIV-1/2 Detect and the reference method.

Diagnostic sensitivity and specificity in neonatal samples Diagnostic sensitivity and specificity for neonatal specimens was determined using a total of 223 heel prick whole blood samples from cohort E. The observed diagnostic sensitivity and specificity [95 % confidence intervals] of m-PIMA™ HIV-1/2 Detect for HIV-1 in heel prick samples was 100 % (18/18) [84.7 %, 100 %] and 100 % (205/205) [98.5 %, 100 %], respectively. No samples reactive for HIV-2 were found in this cohort.

Diagnostic sensitivity in seroconversion panels Diagnostic sensitivity in seroconversion panels was determined using the 10 panels from cohort F. m-PIMA™ HIV-1/2 Detect detected HIV-1 in 46 out of the total 128 panel members compared to 42 out of 128 detected by Abbott ARCHITECT® HIV Ag/Ab Combo. In 4 out of 10 panels m-PIMA™ HIV-1/2 Detect detected HIV-1 M/N earlier, up to 4 days, than the reference. For detailed results see table 1.

CARTRIDGE GUIDE 27

Table 1: Seroconversion Sensitivity

Panel

Number of panel

members tested

Number of panel members detected

Days to first HIV detected Difference in days to first HIV detected

(m-PIMA™ minus

Abbott)


Abbott ARCHITECT® HIV Ag/Ab

Combo


Abbott ARCHITECT® HIV Ag/Ab

Combo

12007 9 6 6 117 117 0

6247 9 3 3 21 21 0

9016 10 3 2 27 30 -3

9018 11 3 3 28 28 0

9020 22 4 3 87 90 -3

9022* 9 3 2 23 25 -2

9024 12 2 1 49 53 -4

9025 12 2 2 85 85 0

9076 9 3 3 66 66 0

9079 25 17 17 40 40 0

Total 128 46 42 543 555

*No Abbott ARCHITECT® HIV Ag/Ab Combo results were provided for the samples 9022-01 and 9022-07, but both Abbott PRISM HIV Ag/Ab Combo and Abbott Murex HIV-1 Ab/Ag Combo were non-reactive.

Diagnostic specificity on frozen whole blood and plasma samples Diagnostic specificity of a test is defined as the proportion of disease-free subjects who have a negative test result and is expressed as a proportion or percentage. Diagnostic specificity was determined using a total of 600 venous whole blood and 603 plasma samples from cohort G. The observed diagnostic specificity [95 % confidence intervals] of m-PIMA™ HIV-1/2 Detect for venous whole blood and plasma samples from presumably healthy donors was 100 % (600/600) [99.51 %, 100 %] and 100 % (603/603) [99.50 %, 100 %], respectively.


Analytical sensitivity/ Limit of Detection m-PIMA™ HIV-1/2 Detect was designed to achieve analytical sensitivities for all three analytes of 4000 cp/mL. During an in-house study at Alere Technologies the analytical sensitivity of m-PIMA™ HIV-1/2 Detect was determined by analyzing the lower limit of detection for each analyte (HIV-1 group M/N, HIV-1 group O and HIV-2). The limit of detection is the number of copies/mL or international units/mL, where the true detection rate is 95 % and was calculated with a Probit regression. Cartridges from three different lots were used. Commercially obtained HIV-1 group M and HIV-2 group A was used. For HIV-1 group O, virus was purified from cell culture supernatant at Alere Technologies GmbH. These analytes were spiked at defined concentration into HIV negative venous whole blood samples from cohort H at concentrations outlined in tables 2, 3 and 4. During the WHO evaluation of m-PIMA™ HIV-1/2 Detect for listing on the WHO list of prequalified in vitro diagnostic products the limit of detection was determined using the WHO 3rd HIV-1 International Standard spiked in whole blood.(31) The conversion factors between virus RNA copies and International Units (IU) are 1:1.67 for HIV-1 group M/N based on the 1st HIV-1 WHO International Standard and 1:0.55 for HIV-2 group A based on the 1st HIV-2 WHO International Standard.

Note: Due to the lack of a reference material for HIV-1 group O, no conversion into IU was possible.

The concentrations in cp/mL and IU/mL [95 % confidence intervals] of virus RNA that can be detected with a positivity rate greater than 95 % as determined by Probit analysis are as follows:*

HIV-1 group M (IIIB Strain): 2491 cp/mL [2046 cp/mL, 3319 cp/mL] and 4160 IU/mL [3417 IU/mL, 5543 IU/mL] HIV-1 group M (WHO 3rd Int. Standard): 1759 cp/mL [1286 cp/mL, 3640 cp/mL] and 2937 IU/mL [2147 IU/mL, 6079 IU/mL] HIV-1 group O (MVP5180 Strain): 943 cp/mL [790 cp/mL, 1262 cp/mL] HIV-2 group A (NIHZ Strain): 952 cp/mL [794 cp/mL, 1239 cp/mL] and 524 IU/mL [437 IU/mL, 681 IU/mL]

*Representative data: results in individual laboratories may vary from these data.

CARTRIDGE GUIDE 29

Table 2: HIV-1 group M (IIIB Strain)

Concentration (cp/mL) N valid N detected Percent detected

640 83 44 53%

1080 79 52 66%

1920 82 74 90%

3320 80 79 99%

5760 82 82 100%

10000 85 85 100%

Table 3: HIV-1 group O (MVP5180 Strain)

Concentration (cp/mL) Nvalid N detected Percent detected

400 74 48 65%

720 80 67 84%

1240 72 72 100%

2120 81 81 100%

3720 85 85 100%

6440 80 80 100%

Table 4: HIV-2 group A (NIHZ Strain)

Concentration (cp/mL) Nvalid N detected Percent detected

240 78 30 38%

400 83 56 67%

720 81 70 86%

1240 78 77 99%

2200 81 81 100%

3800 78 78 100%


Analytical specificity Analytical specificity of a test is defined as the ability to detect only the intended target and that the detection of that target is not affected by cross-reactivity or interfering substances. Cross-reactivity refers to potentially interfering organisms, i.e. other pathogens. Interfering substances refer to endogenous substances that may occur under specimen-related conditions like noninfectious diseases, medical conditions or exogenous substances such as drugs. These substances were either spiked into the samples or already detectable in commercially available sample panels. HIV negative samples from cohort H were spiked with defined amounts of HIV-1 group M subtype B (strain IIIB), HIV-1 group O (strain MVP5180), and HIV-2 group A (strain NIHZ) purified virus (one analyte per sample) to reach a concentration of 12000 cp/mL. Drug interference was tested by adding three times Peak Plasma Level into whole blood.

Cross-Reactivity The susceptibility of m-PIMA™ HIV-1/2 Detect to cross reactivity with relevant pathogenic organisms was evaluated for whole blood, plasma and serum samples. Cross-reactants included pathogens that frequently occur in co-infections with HIV, but also in normal human flora and include viruses, fungi, protozoa and bacteria (see tables 5 and 6).

Table 5: List of pathogens: non-clinical samples

Viruses Bacteria

HTLV-1 HTLV-2 HBV HCV HAdV HSV-1 (HHV-1) HSV-2 (HHV-2) VZV (HHV-3) EBV (HHV-4) HCMV (HHV-5) HHV-6

Salmonella Enteritidis Salmonella Typhimurium Salmonella Paratyphi Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus mutans MSSA MRSA Chlamydia pneumoniae Escherichia coli Propionibacterium acnes

Fungi Protozoa

Candida albicans Cryptococcus neoformans Pneumocystis jirovecii

Toxoplasma gondii

CARTRIDGE GUIDE 31

Table 6: List of pathogens: clinical samples

Organism/ Agent Number of Patient Samples

Treponema pallidum (mixed antibody titer panels)*

10

HCV (serological and NAT pos)** 10

HBV (serological and NAT pos)**

10

HCMV EBV HSV-1 HSV-2 Rubella Virus Toxoplasma gondii (IgG pos)*

12

* confirmed antibody positive samples ** confirmed nucleic acid and antibody positive samples

A total of 26 pathogens provided as non-clinical samples (purified pathogen or purified genomic DNA) have been tested with at least 10 replicates with m-PIMA™ HIV-1/2 Detect. In a total of 304 test runs with HIV-negative and 306 test runs with spiked HIV-positive samples no cross- reactivity with the tested organisms was observed. No false positive HIV results were obtained for any HIV negative samples, and no false negative for HIV positive samples (for all three analytes). In addition 42 clinical samples (9 different pathogens) have been tested for cross-reactivity with the m-PIMA™ HIV-1/2 Detect test. No false positive HIV results were obtained for any HIV negative samples, and no false negative for HIV positive samples (for all three analytes). None of the pathogens revealed cross-reaction with the m-PIMA™ HIV-1/2 Detect test.

Endogenous Interfering Substances and Medical Conditions The susceptibility of m-PIMA™ HIV-1/2 Detect to interference by elevated levels of endogenous substances and several medical conditions was evaluated for plasma and serum samples (see table 7).


Table 7: List of endogenous substances or samples from donors with medical conditions

Clinical Sample Number of Patients

Double-stranded DNA Anti-nuclear antibodies (1:320-1:10000 titer) Bilirubin (5.1-13.4 mg/dL) Cholesterol (99-220 mg/dL) Contraceptive pill Ovarian cancer Renal failure Rheumatoid factor (295-7900 IU/mL) Third trimester pregnancy Total T3 Type II Diabetes IV drug abuser Non-viral liver disease

10 10 10 10 10 10 10 10 10 10 10 10 10

A total of 130 different clinical samples (representing 13 different clinical conditions) have been used for interference testing with m-PIMA™ HIV-1/2 Detect. Of 130 test runs with HIV-negative samples, no false positive results for all three analytes were generated. Of 130 test runs with spiked HIV-positive samples, no false negative results for all three analytes were generated. No interference from endogenous substances or medical conditions was observed.

Drug interference The susceptibility of m-PIMA™ HIV-1/2 Detect to interference by drugs commonly prescribed to HIV infected individuals was evaluated for plasma samples (see table 8).

CARTRIDGE GUIDE 33

Table 8: List of drugs

HIV drugs

Protease Inhibitors Lopinavir, LPV Ritonavir

Nucleoside/Nucleotide Analogue Inhibitors of Reverse Transcriptase Abacavir sulfate, ABC Emtricitabine, FTC Stavudine, d4T Tenofovir disoproxil fumarate, TDF Lamivudine, 3TC Zidovudine, AZT

Non-Nucleoside/Nucleotide Analogue Inhibitors of Reverse Transcriptase Efavirenz, EFV Nevirapine, NVP

Integrase Inhibitors Raltegravir, RAL

HCV/HBV drugs Compounds for treatment of Herpes Viruses

Immune Modulator Ribavirin Peginterferon alfa-2a Peginterferon alfa-2b

Nucleoside Analogues Acyclovir Ganciclovir

Compounds for treatment/ prevention of opportunistic infections in HIV disease

Anti Fungal Fluconazole

Anti Fungal/ Bacterial Co-trimoxazole

Anti Mycobacterial Isoniazid Rifampicin Pyrazinamide Ethambutol Streptomycin

Of 284 test runs with HIV-negative samples, no false positive results for all three analytes were generated. Of 280 test runs with spiked HIV-positive samples, no false negative results for all three analytes were generated. No interference by drugs was observed.

Genotype/ subtype testing The analytical performance of m-PIMA™ HIV-1/2 Detect with HIV-1 and HIV-2 subtypes was evaluated by testing 20 HIV-1 isolates (group M subtypes A through H, group N, group O and Circulating Recombinant Forms) and 8 HIV-2 isolates (HIV-2 group A, B, A/B and an indeterminate subtype). All isolates used in this study were members of subtype panels provided by the German National Reference Center for Retroviruses (GNRCR), Erlangen, Germany.


Viruses were cultivated on cells and supernatants were diluted in HIV-negative plasma and quantified using different real time PCR assays at GNRCR. HIV-samples were originally obtained from virus isolates contributed by the NIH AIDS Research and Reference Reagent Program, USA or from the Program EVA Centre for AIDS Reagents, NIBSC, UK. The specimens were used at Alere Technologies GmbH without further dilution. All subtypes were successfully detected by m-PIMA™ HIV-1/2 Detect. Neither false positive nor false negative results for HIV-1 group M/N, HIV-1 group O or HIV-2 were observed. For details on the tested isolates see tables 9 and 10:

Table 9: HIV-1 Group and Subtype Detection of the m-PIMA™ HIV-1/2 Detect test

m-PIMA™ HIV-1/2 Detect (Ndetected/Nvalid)

Groups/Subtypes Isolate HIV-1 M/N HIV-1 O HIV-2

Group M/Subtype A 92UG029 10/10 0/10 0/10

Group M/Subtype A 00KE_KER2018 10/10 0/10 0/10

Group M/Subtype B 92TH026 10/10 0/10 0/10

Group M/Subtype B 90TH_BK132 10/10 0/10 0/10

Group M/Subtype C 92BR025 10/10 0/10 0/10

Group M/Subtype C 99ET_14 11/11 0/11 0/11

Group M/Subtype D 92UG021 10/10 0/10 0/10



Group M/Subtype CRF01_AE 92TH022 10/10 0/10 0/10

Group M/Subtype F 93BR029 10/10 0/10 0/10

Group M/Subtype F 93BR020 10/10 0/10 0/10

Group M/Subtype G RU570 10/10 0/10 0/10

Group M/Subtype G VI557 10/10 0/10 0/10

Group M/Subtype G/H VI525 10/10 0/10 0/10

Group M/Subtype CRF02_AG 01CM0005BBY 10/10 0/10 0/10

Group M/Subtype CRF02_AG 01CM0008BBY 10/10 0/10 0/10

Group N YBF 30 10/10 0/10 0/10

Group O MVP5180 0/10 10/10 0/10

Group O CA-9 0/10 10/10 0/10

CARTRIDGE GUIDE 35

Table 10: HIV-2 Group Detection of the m-PIMA™ HIV-1/2 Detect test

m-PIMA™ HIV-1/2 Detect (Ndetected / Nvalid)

Groups Isolate HIV-1 M/N HIV-1 O HIV-2

Group A HIV-2 CDC77618 0/10 0/10 10/10

Group A HIV-2 CDC310072 0/10 0/10 10/10

Group A HIV-2 7924A 0/10 0/10 10/10

Group A HIV-2 60415K 0/10 0/10 10/10

Group A HIV-2 CBL-23/H9 0/10 0/10 10/10

Group A/B HIV-2 7312A 0/10 0/10 10/10

Group B HIV-2 CDC310319 0/10 0/10 10/10

indeterminate HIV-2 MIR 0/10 0/10 10/10

Matrix effects To evaluate potential effects of sample matrix on m-PIMA™ HIV-1/2 Detect performance, spiked HIV negative samples and samples from HIV positive cohorts were tested.

Matrix effect in spiked samples Fresh matched venous whole blood and plasma samples from cohort H were spiked with virus preparations of HIV-1 group M subtype B (strain IIIB) at a concentration of 12000 cp/mL. The samples were analyzed with m-PIMA™ HIV-1/2 Detect at 3 days with two runs per day on 20 analyzers. Valid tests (venous whole blood: n=56; plasma: n=59) were used to analyze the matrix effect. For all tests on venous whole blood and matching plasma spiked with 12000 cp/mL HIV-1 M subtype B (strain IIIB), HIV-1 M/N was 100 % successfully detected with m-PIMA™ HIV-1/2 Detect. No influence of blood cells and blood cell components on the detection rate was observed. There were no false positive results for HIV-1 O and HIV-2. The results are considered to be representative for all analytes of the m-PIMA™ HIV-1/2 Detect test (HIV-1 group M/N, HIV-1 group O and HIV-2).

Matrix effect in patient samples with viral loads ≥ 2491 cp/mL Matrix effect was determined using a total of 235 matched pairs of venous whole blood and plasma samples, and 74 matched pairs of venous whole blood and capillary blood samples from cohorts A, B and C with corresponding plasma viral loads above the limit of detection of m-PIMA™ HIV-1/2 Detect (≥ 2491 cp/mL determined with Roche Cobas®). For matched pairs of venous whole blood and plasma samples there was 100 % agreement (CI for difference in sensitivity -1.8 %, +1.8 %) between the m-PIMA™ HIV-1/2 Detect test results.


For matched pairs of venous whole blood and capillary blood samples there was 98.65 % agreement (CI for difference in sensitivity -7.7 %, +4.2 %) between the m-PIMA™ HIV-1/2 Detect test results (please also refer to the limitation section on page 23). While only HIV-1 M/N was detected in the samples from these cohorts, the results are considered to be representative for all analytes of the m-PIMA™ HIV-1/2 Detect test (HIV-1 group M/N, HIV-1 group O and HIV-2).

Multiplex assay To evaluate potential effects of the presence of multiple analytes at different concentrations in the same sample on m-PIMA™ HIV-1/2 Detect performance, defined concentrations of HIV-1 group M/N and O and HIV-2 virus preparations were spiked into HIV negative whole blood samples of presumably healthy European donors from cohort H according to the table below.

Table 11: HIV-concentrations used to prepare multiplex samples

HIV Concentration

Spiked sample

Log cp/mL HIV-1 M/N

Log cp/mL HIV-1 O

Log cp/mL HIV-2

low 1 5.08 4.08 4.08

2 4.08 5.08 4.08

3 4.08 4.08 5.08

high 4 7.00 6.00 6.00

5 6.00 7.00 6.00

6 6.00 6.00 7.00

For all 203 tests on multiplex samples at different concentrations, HIV-1 M/N, HIV-1 O and HIV-2 were 100 % successfully detected with m-PIMA™ HIV-1/2 Detect. No interference of the different analytes on each other’s detectability (at the spiked concentrations) was observed.

CARTRIDGE GUIDE 37

Carryover Potential sample carryover in the automated m-PIMA™ Analyser when used with the m-PIMA™ HIV-1/2 Detect test was evaluated by testing high titer HIV-1 (strain IIIB) samples (at a target concentration of 3x107 cp/mL) interspersed with negative samples (n=144). m-PIMA™ HIV-1/2 Detect test did not exhibit detectable carryover from high positive samples to negative samples.

Precision To evaluate the precision of the m-PIMA™ HIV-1/2 Detect test, 6 HIV negative whole blood samples from cohort H were spiked with virus preparations of HIV-1 group M subtype B (strain IIIB) at a concentration of 8000 cp/mL. For all 348 tests on spiked venous whole blood samples performed on 8 different m-PIMA™ Analyser over the course of 6 days HIV-1 M/N was 100 % successfully detected with m-PIMA™ HIV-1/2 Detect. There were no false positive results for HIV-1 O and HIV-2. The results are considered to be representative for all analytes of the m-PIMA™ HIV-1/2 Detect test (HIV-1 group M/N, HIV-1 group O and HIV-2).

TECHNICAL SUPPORTFor Technical Support please contact your local distributor or call the respective number for your region:

EuropeRussia & CIS

+44 161 483 5884 [email protected]

Africa +27 21 5315 999 [email protected]

Asia Pacific +61 7 3363 7166 [email protected]

India +91 11 45089400 [email protected]

Latin America+57 2 6618916 +57 2 6618797

[email protected]


REFERENCES(1) WHO. Antiretroviral therapy of HIV infection in infants and children: towards universal access:

recommendations for a public health approach - 2010 revision. Geneva: WHO; 2010. Available at: http://apps.who.int/medicinedocs/documents/s18809en/s18809en.pdf.

(2) Jani I.V., Meggi B., Mabunda N., et al. 2014. Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test. J Acquir Immune Defic Syndr 67(1):e1-4

(3) Bruisten S., van Gemen B., Koppelman M., et al. 1993. Detection of HIV-1 distribution in different blood fractions by two nucleic acid amplification assays. AIDS Res Hum Retroviruses 9:259-65.

(4) Lee T.H., Stromberg R.R., Heitman J.W., et al. 1998. Distribution of HIV type 1 (HIV-1) in blood components: detection and significance of high levels of HIV-1 associated with platelets. Transfusion 38:580-8.

(5) Torre D. and Pugliese A. 2008. Platelets and HIV-1 infection: old and new aspects. Curr HIV Res 6:411-8.

(6) Beck Z., Jagodzinski L.L., Eller M.A., et al. 2013. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients. PLoS One 8:e81002.

(7) Zhu T., Muthui D., Holte S., et al. 2002. Evidence for human immunodeficiency virus type 1 replication in vivo in CD14 (+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol 76:707-16.

(8) Kaiser P., Joos B., Niederost B., et al. 2007. Productive human immunodeficiency virus type 1 infection in peripheral blood predominantly takes place in CD4/CD8 double-negative T lymphocytes. J Virol 81:9693-706.

(9) Cena M., Schwachsa N., Garcia M.N.,et al. 2004. Determination of HIV-1 p24 antigen associated with erythrocytes: potential uses. Int Conf AIDS. 2004 Jul 11-16. 15:abstract no. B11460.

(10) Garcia M.N., dos Ramos Farías M.S., Schvachsa N.,et al. 2006. Detection of HIV-1 antigen associated to erythrocytes in patients with undetectable viral load in plasma for more than one year. Poster presentation from 2006 International Meeting of The Institute of Human Virology Baltimore, USA. 17-21 November, 2006. Retrovirology 3(Suppl 1):P19.

(11) Hess C., Klimkait T., Schlapbach L., et al. 2002. Association of a pool of HIV-1 with erythrocytes in vivo: a cohort study. Lancet 359:2230-4.

(12) Arens M., Joseph T., Nag S. et al. 1993. Alterations in spliced and unspliced HIV-1-specific RNA detection in peripheral blood mononuclear cells of individuals with varying CD4-positive lymphocyte counts. AIDS Res Hum Retroviruses 9:1257-63.

(13) Bagnarelli P., Menzo S., Valenza A., et al. 1992. Molecular profile of human immunodeficiency virus type 1 infection in symptomless patients and in patients with AIDS. J Virol 66:7328-35.

(14) Furtado M.R., Murphy R. and Wolinsky S.M. 1993. Quantification of human immunodeficiency virus type 1 tat mRNA as a marker for assessing the efficacy of antiretroviral therapy. Infect Dis 167:213-6.

(15) Graziosi C., Pantaleo G., Butini L., et al. 1993. Kinetics of human immunodeficiency virus type 1 (HIV-1) DNA and RNA synthesis during primary HIV-1 infection. Proc Natl Acad Sci U S A 90:6405-9.

CARTRIDGE GUIDE 39

(16) Gupta P., Kingsley L., Armstrong J., et al. 1993. Enhanced expression of human immunodeficiency virus type 1 correlates with development of AIDS. Virology 196:586-95.

(17) Michael N.L., Vahey M., Burke D.S., et al. 1992. Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease. J Virol 66:310-6.

(18) Patterson B.K., Till M., Otto P., et al. 1993. Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry. Science 260:976-9.

(19) Schnittman S.M., Greenhouse J.J., Lane H.C., et al. 1991. Frequent detection of HIV-1-specific mRNAs in infected individuals suggests ongoing active viral expression in all stages of disease. AIDS Res Hum Retroviruses 7:361-7.

(20) Seshamma T., Bagasra O., Trono D., et al. 1992. Blocked early-stage latency in the peripheral blood cells of certain individuals infected with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89:10663-7.

(21) Steinmetzer K., Seidel T., Stallmach A., et al. 2010. HIV load testing with small samples of whole blood. J Clin Microbiol 48:2786-92.

(22) Ullrich T., Ermantraut E., Schulz T., et al. 2012. Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization. PLoS ONE 7(4): e35438. doi:10.1371/journal.pone.0035438

(23) Soderlund, H. 1990. DNA hybridization: comparison of liquid and solid phase formats. Ann Biol Clin (Paris) 48:489-91.

(24) UK NHS. Guidelines for Newborn Blood Spot Sampling. February 2012. Available at: http://newbornbloodspot.screening.nhs.uk/bloodspotsampling#fileid11952

(25) WHO. WHO guidelines on drawing blood: best practices in phlebotomy. Geneva: WHO; 2010. Available at: http://whqlibdoc.who.int/publications/2010/9789241599221_eng.pdf

(26) CLSI GP42-A6 Procedures and Devices for the Collection of Diagnostic Capillary Blood Specimens; Approved Standard-Sixth Edition. Clinical and Laboratory Standards Institute; 2008.

(27) CLSI GP41.Collection of Diagnostic Venous Blood Specimens; Approved Standard-7th Edition, Clinical and Laboratory Standards Institute, 2017.

(28) Chudy M, Kress J, Halbauer J, et al. 2014. Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany. Transfus Med Hemother 41:45-51.

(29) Korn K, Weissbrich B, Henke-Gendo C, et al. 2009. Single-point mutations causing more than 100-fold underestimation of human immunodeficiency virus type 1 (HIV-1) load with the Cobas TaqMan HIV-1 real-time PCR assay. J Clin Microbiol 47:1238-40.

(30) Chang M., Gottlieb G.S., Dragavon J.A., et al. 2012. Validation for clinical use of a novel HIV-2 plasma RNA viral load assay using the Abbott m2000 platform. J Clin Virol 55:128-133.

(31) WHO Prequalification of In Vitro Diagnostics Public Report for Alere™ q HIV-1/2 Detect PQDx 0226-032-00. June/2016, version 2.0. Geneva: WHO; 2016. Available at: http://www.who.int/diagnostics_laboratory/evaluations/pq-list/hiv-vrl/public_report/en/

Printed on 100 % recycled paper.

Version 12PI-m-PIMA-01-12-EN

Revision date: 20-Jan-2020

Abbott Rapid Diagnostics Jena GmbHOrlaweg 1D-07743 Jena, Germanywww.abbott.com/poct

© 2020 Abbott. All rights reserved.

All trademarks referenced are trademarks of either the Abbott group of companies or their respective owners.

EN How to interpret m-PIMA™ HIV-1/2 Detect test results

HIV RNAUndetected

HIV-1 M/N RNADetected

HIV-1 O RNADetected

HIV-2 RNADetected

Patient is HIV positive

if one or more of the three results are Detected

Test Report



HIV-1 M/N

HIV-1 O

HIV-2

Undetected

Undetected

Undetected

Result No. 107



Signature


NAT-04000035

0.26.1


Test Report



HIV-1 M/N

HIV-1 O

HIV-2

Undetected

Detected

Undetected

Result No. 107



Signature


NAT-04000035

0.26.1


Test Report



HIV-1 M/N

HIV-1 O

HIV-2

Detected

Undetected

Undetected

Result No. 107



Signature


NAT-04000035

0.26.1


Test Report



HIV-1 M/N

HIV-1 O

HIV-2

Undetected

Undetected

Detected

Result No. 107



Signature


NAT-04000035

0.26.1


F Comment interpréter les résultats du test m-PIMA™ HIV-1/2 Detect

ARN du VIH Non détecté

ARN du VIH-1 M/NDétecté

ARN du VIH-1 ODétecté

ARN du VIH-2Détecté

Le patient est VIH positif

si un ou plus des trois résultats sont Détecté

Rapport du Test


ID Echantillon23-03-2018-ABC

VIH-1 M/N

VIH-1 O

VIH-2

Non détecté

Non détecté

Non détecté

N° Résultat 123

Date / Heure 2018-06-23 15:50ID CartoucheOpérateurN° de sérieLogcielCQ

Détection échantillonDispositifContrôle positif VIH-1Contrôle positif VIH-2Contrôle négatifAnalyse

Signature


NAT-04000035

0.26.1

RéussiRéussiRéussiRéussiRéussiRéussi

Rapport du Test



VIH-1 M/N

VIH-1 O

VIH-2

Non détecté

Détecté

Non détecté

N° Résultat 123



Signature


NAT-04000035

0.26.1


Rapport du Test



VIH-1 M/N

VIH-1 O

VIH-2

Détecté

Non détecté

Non détecté

N° Résultat 123



Signature


NAT-04000035

0.26.1


Rapport du Test



VIH-1 M/N

VIH-1 O

VIH-2

Non détecté

Non détecté

Détecté

N° Résultat 123



Signature


NAT-04000035

0.26.1


PT Como interpretar os resultados do teste m-PIMA™ HIV-1/2 Detect

RNA de VIHNão detetado

RNA de VIH-1 M/NDetetado

RNA de VIH-1 ODetetado

RNA de VIH-2Detetado

O paciente é HIV positivo

se um ou mais dos três resultados forem Detetado

Relatório do teste


ID da amostra ID23-03-2018-ABC

VIH-1 M/N

VIH-1 O

VIH-2

Não detetado

Não detetado

Não detetado

Resultado n.º 107

Data/Hora 2018-06-23 15:50ID de cartuchoOperadorRef. dispositivoSoftwareCQ

Deteção de amostraDispositivoControlo positivo de VIH-1Controlo positivo de VIH-2Controlo negativoAnálise

Assinatura


NAT-04000035

0.26.1

AprovadoAprovadoAprovadoAprovadoAprovadoAprovado

Relatório do teste



VIH-1 M/N

VIH-1 O

VIH-2

Não detetado

Detetado

Não detetado

Resultado n.º 107



Assinatura


NAT-04000035

0.26.1


Relatório do teste



VIH-1 M/N

VIH-1 O

VIH-2

Detetado

Não detetado

Não detetado

Resultado n.º 107



Assinatura


NAT-04000035

0.26.1


Relatório do teste



VIH-1 M/N

VIH-1 O

VIH-2

Não detetado

Não detetado

Detetado

Resultado n.º 107



Assinatura


NAT-04000035

0.26.1


ES Cómo interpretar los resultados del test m-PIMA™ HIV-1/2 Detect

ARN de VIHNo detectado

ARN de VIH-1 M/NDetectado

ARN de VIH-1 ODetectado

ARN de VIH-2Detectado

Paciente es VIH positivo

si uno o más de los tres resultados son Detectado

Informe de prueba


ID de muestra23-03-2018-ABC

VIH-1 M/N

VIH-1 O

VIH-2

No detectado

No detectado

No detectado

Resultado Nº 107

Fecha/Hora 2018-06-23 15:50ID del cartuchoOperadorNº serie dispositivoSoftwareQC

Detección de muestraDispositivoControl de VIH-1 positivoControl de VIH-2 positivoControl negativoAnálisis

Firma


NAT-04000035

0.26.1

AprobadoAprobadoAprobadoAprobadoAprobadoAprobado

Informe de prueba



VIH-1 M/N

VIH-1 O

VIH-2

No detectado

Detectado

No detectado

Resultado Nº 107



Firma


NAT-04000035

0.26.1


Informe de prueba



VIH-1 M/N

VIH-1 O

VIH-2

Detectado

No detectado

No detectado

Resultado Nº 107



Firma


NAT-04000035

0.26.1


Informe de prueba



VIH-1 M/N

VIH-1 O

VIH-2

No detectado

No detectado

Detectado

Resultado Nº 107



Firma


NAT-04000035

0.26.1


No HIVdetected

Le VIH n‘est pas détecté

VIHno

detectado

VIH não

detetado

This Test Report format is displayed for test runs performed on m-PIMA™ Analyser software version 0.26.2 or lower. Ce format de rapport du test est affiché pour les tests effectués sur le logiciel m-PIMA™ Analyser version 0.26.2 ou inférieure.

Este formato de relatório do teste é exibido para execuções de teste realizadas na versão 0.26.2 ou inferior do software m-PIMA™ Analyser. Este formato de Informe de prueba se muestra para las pruebas realizadas con el software m-PIMA™ Analyser versión 0.26.2 o inferior.

Important safety information. Read carefully. Please also refer to the m-PIMA™ HIV-1/2 Detect Cartridge Guide (PI-m-PIMA-01).

Informations de sécurité importantes. Lisez attentivement, s. v. p. Veuillez aussi consulter le Guide de la cartouche m-PIMA™ HIV-1/2 Detect (PI-m-PIMA-01).

Aviso importante de segurança. Leia com atenção. Por favor, consulte também o Guia do cartucho m-PIMA™ HIV-1/2 Detect (PI-m-PIMA-01).

Información de seguridad importante. Lea detenidamente. Por favor también consulte la guía del cartucho m-PIMA™ HIV-1/2 Detect (PI-m-PIMA-01).

Revision date/ Date de révision/ Data da revisão/ Fecha de revisión: 16-Jan-2020 AI-m-PIMA-03-04-Multi

© 2020 Abbott. All rights reserved. All trademarks referenced are trademarks of either the Abbott group of companies or their respective owners.

© 2020 Abbott. Tous droits réservés.Toutes les marques de commerce citées sont des marques de commerce du groupe de sociétés Abbott ou de leurs détenteurs respectifs.

© 2020 Abbott. Todos os direitos reservados.Todas as marcas referenciadas são marcas comerciais de empresas do grupo Abbott ou de seus respectivos proprietários

© 2020 Abbott. Todos los derechos reservados.Todas las marcas registradas mencionadas en este documento son marcas registradas pertenecientes al grupo de empresas Abbott o a sus correspondientes titulares.

EN

F

PT

ES

Abbott Rapid Diagnostics Jena GmbHOrlaweg 1D-07743 Jena, Germany/ Allemagne/ Alemanha/ Alemaniawww.abbott.com/poct

m-PIMA™ ANALYSER USER GUIDE

EN

The m-PIMA™ Analyser is a portable automated bench-top analyzer for processing m-PIMA™ test cartridges and may be used in any laboratory and non-laboratory environment that meets the requirements specified in this document. The m-PIMA™ Analyser can be operated on external power, with an internal rechargeable battery protecting it against power fluctuations and is also suitable for near-patient testing.

For more product information about the m-PIMA™ Analyser and available test cartridges please go to www.abbott.com/poct

m-PIMA™ Analyser

Index of Symbols

CE Mark Manufacturer

In vitro diagnostic medical device Serial number

Catalogue number Direct current (DC)

Lithium-Ion Battery To keep dry

This product must be recycled or discarded according to applicable local and national regulations.

Attention symbol. Indicates important information. Read the accompanying text carefully.

Temperature limitation Consult instructions for use

Don’t pull on cord Pull at plug

50ºC2ºC

m-PIMA™ ANALYSER USER GUIDE 3

1

2

3

4

5

6

7

8

9

10

1 INTRODUCTION

2 GETTING STARTED

3 HOME

4 RUNNING A TEST

5 ARCHIVE

6 SETTINGS

7 DEVICE

8 POWER OFF & STORAGE

9 TECHNICAL SUPPORT & ERROR CODES

10 WARNINGS & ERROR MESSAGES

4

6 1 INTRODUCTION6 Intended Use6 User Profile6 Test Principle6 Data Handling7 m-PIMA™ Analyser Specifications8 Declaration of Conformity 8 Unpacking, Installation and Transport8 Calibration9 Maintenance and Cleaning9 Components and optional items10 Safety Warnings and Precautions12 The m-PIMA™ Analyser at a Glance

13 2 GETTING STARTED13 Setting up the m-PIMA™ Analyser14 Charging the m-PIMA™ Analyser15 m-PIMA™ Analyser Status Lights15 Power Status Light16 Charging Status Light16 Process Status Light17 m-PIMA™ Analyser User Interface17 m-PIMA™ Analyser Display 18 Navigation18 Explanation of Icons19 Data Entry19 Screen Type Description21 The Battery Symbol

22 3 HOME22 Menu Overview

23 4 RUNNING A TEST23 How to initiate a Test24 How to insert an m-PIMA™ Test Cartridge25 How to enter an Operator27 How to enter a Sample ID28 Analysis in Progress28 Analysis Completed29 Printing Results immediately after Analysis30 The m-PIMA™ Test Report31 During Analysis31 How to Change Operator and Sample ID32 How to Abort an Analysis

TABLE OF CONTENTS


34 5 ARCHIVE35 View Results35 Select Results36 Action Menu36 Action Menu: Print38 Action Menu: Export38 Export Options41 Action Menu: Delete

42 6 SETTINGS42 Operator List43 Enter an Operator 44 Delete an Operator45 Date and Time46 Languages47 Advanced Settings48 Connectivity48 Calibrate Screen50 Test Mode53 Signal Tone

54 7 DEVICE54 Device Info56 Service Export58 Software Update

59 8 POWER OFF & STORAGE60 Deinstallation60 m-PIMA™ Analyser Storage and Recharging Intervals

61 9 TECHNICAL SUPPORT & ERROR CODES 61 Technical Support62 Error Codes

66 10 WARNINGS & ERROR MESSAGES66 Archive Information67 Power Warnings68 Export Errors70 Printer Warning70 Printer Error

1

1 INTRODUCTION6

1 INTRODUCTION

Intended Use

The m-PIMA™ Analyser is a portable automated bench-top analyser for processing m-PIMA™ test cartridges. The m-PIMA™ Analyser is suited to be used in laboratory as well as in non-laboratory environments. The instrument is classified as in vitro diagnostic device.

User Profile

User profiles are described in detail in the respective Package Inserts (PI) of the m-PIMA™ test cartridges.

Test Principle

An m-PIMA™ test consists of a disposable test cartridge containing both dried reagents and liquid buffer and the m-PIMA™ Analyser.Depending on the test cartridge used, appropriate volumes of test sample are applied onto the cartridge.During processing of the test, data is recorded, analysed and interpreted using software embedded within the instrument. Upon completion of the test the cartridge is removed from the m-PIMA™ Analyser and a test result is displayed.For detailed information on the test principle of the individual assay, please refer to the respective Cartridge Guides.

Data Handling

The m-PIMA™ Analyser provides for data entry (Operator, Sample ID), archiving and connectivity to printers, data storage media and remote FTP servers.You can save all results in the on-board archive and retrieve or download and export them at any time after the test.Additionally, you can print a Test Report using the attached external USB Printer.


1m-PIMA™ Analyser Specifications

Device

Dimensions W 20 cm × H 22 cm × D 31 cm

Weight 8 kg

Detection system LED illumination and CCD-based detection

Controlssample detection, control of cartridge expiry date, automated cartridge identification, internal process controls

Display graphical display, colour, VGA 480 × 640 pixel

User interface touch screen (resistive)

Languages (display) English, French, German, Portuguese, Spanish

Memory data storage capacity of 1000 tests

Protection class III

Degree of protection IP 20

Climate conditions

Operating10 – 40 °C at max. 85 % humidity, altitude 0 – 2000 m NN (0 – 6500 feet), 800 – 1013 hPa

Storage 2 – 50 °C

Transport 2 – 50 °C at max. 95 % humidity

Environment no direct sunlight, humidity and dust

Power

Mains power 110 – 220 V (A / C) at 47 – 63 Hz, max. 4 A

Power supply DC 24 V/ 6 A/ 144 W

Overvoltage category II

Internal battery rechargeable Lithium-Ion battery

Power supply type PMP 220 SF-14 (protection class II)

1

1 INTRODUCTION8

Declaration of Conformity

The m-PIMA™ Analyser complies with Directives 98/79/EC and 2011/65/EU and was tested according to IEC 61010-1, IEC 61010-2-101, IEC 61326-1 and IEC 61326-2-6.

Unpacking, Installation and Transport

Unpack the m-PIMA™ Analyser and place it safely on a clean, flat, level and stable surface. Inspect for any obvious sign of damage. Report any damage immediately to your local distributor.Allow 5 – 10 cm space on the back of the instrument to ensure free ventilation.Please use the device handle to lift the instrument, considering the instrument weight. If you transported or moved the m-PIMA™ Analyser to areas with different climatic conditions, allow temperature equilibration for at least 30 minutes before turning on the instrument.

Note: Keep the original m-PIMA™ Analyser box in case you need to transport the instrument. Throw the main power switch on the back of the instrument to position ( O ) to prevent accidental start up during transport.

Calibration

The m-PIMA™ Analyser is factory calibrated and does not require any further calibration. However, upon switching on the m-PIMA™ Analyser performs an internal routine to verify calibration and pre-set instrument parameters.


1Maintenance and Cleaning

The m-PIMA™ Analyser requires no user related maintenance.If outer cleaning is required, use cleaning solution containing alcohol (for example 70% ethanol or isopropanol). Soak a paper towel or clean cloth with cleaning solution and wipe the outside of the instrument.

Do not use cleaning solutions containing chlorine bleach or organic solvents other than alcohol. Never clean the inside of the m-PIMA™ Analyser. Always turn off the m-PIMA™ Analyser and disconnect it from any external power source and accessories before cleaning.

Follow the instructions on the clearance certificate included in the instrument box before shipping the m-PIMA™ Analyser to a third party.

Components and optional items

The following items are supplied with your m-PIMA™ Analyser (catalogue no. 27030R001):• Power transformer• Power cord (EU, UK, AUS/ASIA, SA) • m-PIMA™ Analyser User Guide

The following optional items are also available for your m-PIMA™ Analyser:• USB Printer (catalogue no. 27040R007)• Printer Paper I (catalogue no. 26040R009)• Printer Paper II (catalogue no. 26040R010)• PowerDrum (catalogue no. 27040R004)• Connectivity Pack IV (catalogue no. 260400059)• CONNECT Universal Gateway (catalogue no. AC-EU-01/ AC-US-01)

1

1 INTRODUCTION10

Safety Warnings and Precautions

Please read the following safety instructions carefully to avoid any misuse.Only use the m-PIMA™ Analyser as described in this document.

Only use the Power transformer and A/C power cord supplied with the m-PIMA™ Analyser. Any other power supplies can damage the instrument and may cause hazards.

The m-PIMA™ Analyser is designed to be used in combination with m-PIMA™ test cartridges only. Do not insert any other cartridges, test strips or devices into the instrument.

Plug in the power cord only in grounded power sockets.

Place the m-PIMA™ Analyser where you can easily disconnect it from mains A/C power at any time.

Turn the back of the m-PIMA™ Analyser to the front for easy access to ports and main switch. Do not tilt forward the instrument for better access since this may result in considerable damage to the front door and housing.

Do not open the m-PIMA™ Analyser. Any unauthorized opening of the instrument can cause potential hazards and will invalidate warranty claims.

Only insert the USB Printers or other authorized devices, e.g. Connectivity Packs IV into the USB ports of the m-PIMA™ Analyser. Use only one USB storage device at a time.

Only use FAT32 formatted storage/ export devices.

Do not plug in bulky USB devices next to each other since this may damage the USB ports.


1 To ensure proper ventilation do not cover the instrument while switched on.

Only trained and authorized personnel may use the m-PIMA™ Analyser. Abbott is not responsible for any injury or damage caused by improper use.

The m-PIMA™ Analyser must not be moved while an analysis is in progress.

Do not autoclave the m-PIMA™ Analyser!

Follow proper infection control guidelines for handling all human specimens and related items.

Do not dispose of the m-PIMA™ Analyser with domestic waste. For information regarding disposal of the m-PIMA™ Analyser please contact your local distributor.

Operating the m-PIMA™ Analyser at atmospheric pressures outside the specifications (page 7) may result in increased numbers of instrument induced test terminations. Please refer to section 9 for respective Error Codes and actions.

m-PIMA™ test cartridges are for single use only and need to be discarded as biohazard waste after removal. Do not reuse test cartridges.

1

1 INTRODUCTION12

m-PIMA™ Analyser at a Glance

Touch screen

Device handle

Power On

m-PIMA™ Analyser door

Power Status LightCharging Status Light

Process Status Light

LAN port

8

9

10

11

Main power switch

2 × USB ports

Power connector port


2

2 GETTING STARTED

To prevent undesired discharge of the internal battery an energy preservation mode (EP-mode) is implemented by the manufacturer. Before starting to work with your m-PIMA™ Analyser see the following instructions.

Setting up the m-PIMA™ Analyser

• Connect the instrument to A/C power or a compatible external energy source as listed in “Components and optional items” (page 9) before switching on your m-PIMA™ Analyser. When using external power sources also refer to their respective handling instructions.

• Insert the A/C power cord into the power transformer.• Connect the power transformer to the power connector port located at

the back of the instrument. Please note that the power plug can only be inserted in one particular direction. Make sure that the arrow on the flat side of the plug is facing the main power switch (see graphic).

• Connect the power cord to the corresponding A/C power socket. Illumination of the power supply LED indicates the connection to mains power.

• Switch on your m-PIMA™ Analyser using the main power switch on the back of the instrument (position ( I )).

Power connector Power transformer A/C power cord plus tag

2

14 2 GETTING STARTED

Note: Make sure to remove all storage devices before you switch on the m-PIMA™ Analyser.

• Then press the grey Power On button located on the front of the m-PIMA™ Analyser. The EP-mode of the internal battery is now deactivated.

An automated initialization procedure commences and may last for approximately one minute. The screen changes automatically during this procedure. Please refer to section 8 to learn more about shutting down the m-PIMA™ Analyser and re-activation of the EP-mode. If the m-PIMA™ Analyser fails to correctly initialize, an Error Code or an Error Message will be displayed. Please refer to section 9 to learn more about Error Codes and respective actions.

The m-PIMA™ Analyser is ready for use when the «HOME» screen is displayed.

Charging the m-PIMA™ Analyser

Your m-PIMA™ Analyser is supplied with a partly charged battery secured within the instrument to cover power outages. Once the m-PIMA™ Analyser is set up and the battery EP-mode is deactivated the battery will be automatically charged while the instrument is running and connected to an external power supply.Ensure the battery is fully charged before you initiate a test run.Please refer to section 7 for more information about the battery status.

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST


2

Power Status LightThe green power status light on the front of the instrument indicates whether the m-PIMA™ Analyser is turned on and ready to operate.

The appearance of the solid green power status light confirms that the m-PIMA™ Analyser is switched on.

m-PIMA™ Analyser OFF Off

m-PIMA™ Analyser startup/ shut down Flashing

m-PIMA™ Analyser ON Solid

m-PIMA

Power Status Light

Charging Status Light

Process Status Light

m-PIMA™ Analyser Status Lights

Your m-PIMA™ Analyser is equipped with a number of LED indicators to inform you about the current state of the instrument.

2


Charging Status LightOnce the instrument is connected to an external power source and turned on the yellow charging status light located on the front of the instrument will be illuminated, indicating the charging status of the internal battery.

The charging status light will only be illuminated when the m-PIMA™ Analyser is connected to an external power source and turned on. It may take several minutes until the instrument displays the correct charging status.

In order to ensure maximum battery life, charge the internal m-PIMA™ Analyser battery whenever possible. To recharge an empty battery takes approx. 90 minutes.

When your m-PIMA™ Analyser is running on battery power, the battery status is indicated by the battery symbol within the display status line (see page 21).

Process Status LightOn the right side of the m-PIMA™ Analyser door you find the process status light. It is only illuminated during an active analysis process.

No cartridge inserted/ m-PIMA™ Analyser off

Off

Analysis in progress Solid

Analysis done Flashing

m-PIMA™ Analyser not connected to external power Off

m-PIMA™ Analyser battery charging Flashing

m-PIMA™ Analyser battery fully charged Solid


2

Result in 45 minutes.

m-PIMA HIV-1/2 VL

Sample ID

07-11-2019-ABC

ANALYSIS14:562019-11-07

m-PIMA™ Analyser Display (example)

Status LineDate and time are displayed.

Title LineDisplay of screen type and currently active menu or sub menu.

Message LineArea to display menu items, test results, error codes, device activities and messages.

Navigation LineProvides access to the various test functions and menu options.

Please find a more detailed description of the icons on page 18.

m-PIMA™ Analyser User Interface

Your m-PIMA™ Analyser is equipped with a resistive touch screen for displaying information and to interact with the instrument. The touch screen is precalibrated and you may use it with bare or gloved hands alike. In case the touch screen loses its calibration go to page 49 to learn more about how the touch screen of your m-PIMA™ Analyser can be re-calibrated.

2


Explanation of Iconsguides you directly to the «Home» screen where you get access to various menu functions

to scroll through menu lists, archive entries and Test Reports

to scroll through menu lists, archive entries and Test Reports

to confirm all entries or selections or to confirm a message (Information, Warning, Error)

to go back to the previous screen

to abort an active process

to access the print, export, delete and select all option

to open a Test Report in the m-PIMA™ Analyser archive

to print m-PIMA™ Test Reports

to delete entries in the Operator List

Home Cancel

Up Action

Down View

Confirm Print

Back Delete

Navigation

The touch screen user interface facilitates easy navigation between the various menu options.

Activate specific functions by pressing the respective field on the screen.

Use the scroll option for accessing data that is stored in a list format.

ARCHIVE14:51

32

15

8

2019-11-06

89-FG

1-AH-35

62-GU-1

Sample ID# ViewDate

2019-11-06

2019-11-05

2019-11-05

2019-11-04

2019-11-02

2019-10-30

123456789-ABD-576123106

105

75

107 06-11-2019-ABC

2019-11-07

12345-ABG-123

123456789-ABF


2

The majority of screens displayed are Menu screens. Their header is blue.

They display menus and sub menus, lists, actions in progress and results.

SETTINGS14:56

Operator List

Date and Time

Language

Advanced Settings

2019-11-07

Screen Type Description

Throughout the m-PIMA™ Analyser menu structure different types of screens will be displayed.You will find a brief overview in the following.

The different screen types can easily be distinguished by the color of their title/ status line (header). Examples for every screen type are shown below.

Data Entry

Use the alpha-numeric keypad to enter test related data, e. g. Sample IDs.

Switch between capital and lower case letters by pressing or to special characters by pressing [#?+], respectively.

1 2 3 4 5 6 7 8 9 0

Q W E R T Y U I O P

A S D F G H J K L -

Z X C V B N M . _

#?+

1 2 3 4 5 6 7 8 9 0

= / ~ + “ { } < > @

* # % & § ^ [ ] -

\ , ( ) : ! ? . _

ABC

$

2


Cancel current process?

CONFIRMATION15:332019-11-07

YESNO

ERROR15:33

PRINTING FAILED

2019-11-07

Information screens with white headers appear when pressing an inactive grey icon. An icon turns grey if the underlying action is not available at that stage, e.g. the g icon will turn or remain grey as long as no printer is connected to the m-PIMA™ Analyser.

Information screens provide you with further details to continue with your processes.

As a precautionary measure your m-PIMA™ Analyser will ask you to confirm certain decisions, like cancelling active processes.

Confirmation screens are displayed with a yellow header.

Choose either z or y to continue.

Error screens are displayed completely in red. They contain either Error Messages or Error Codes.

Confirming Error screens with i will lead you either back to the previous screen or will open a m-PIMA™ Test Report.

INFORMATION15:33

Connect to USB Printer.

2019-11-07


2

Internal battery low.

Connect to A/C power immediately.

WARNING15:332019-11-07Warning screens alert you about a status

that may limit the functionality of the m-PIMA™ Analyser or an accessory.

Please refer to section 10 for respective Warning screens and actions.

The Battery Symbol

As soon as your m-PIMA™ Analyser is disconnected from mains A/C the internal battery will instantaneously continue to supply the instrument with power. A fully charged battery will provide you with electrical power for the completion of an already started test. The total capacity of the internal battery will decrease with age of the m-PIMA™ Analyser.

The m-PIMA™ Analyser informs you about the change of supply mode with the following information and asks for your active confirmation.

The m-PIMA™ Analyser runs on internal battery.

Connect to A/C power.

WARNING15:332019-11-07• Press i to continue.

The battery symbol will now appear in the status line of every screen.

Additionally the yellow charging status light on the front panel will go off.

3

22 3 HOME

3 HOME

After the initial startup process the «HOME» screen will be displayed as your entry point to the various menu options. Pressing e will guide you directly to the initial «HOME» screen.

Note: During an active test run the e option is not available.

Menu overview

SETTINGS

HOME

Connectivity

Date & Time

Language

Advanced Settings

Calibrate Screen

ARCHIVE

RUN TEST Test Report

DEVICE

Service Export

Test Mode

SignalTone

POWER OFF

Device Info

OperatorList

23

4


4 RUNNING A TEST

How to initiate a Test

The m-PIMA™ test consists of a disposable test cartridge, containing all test reagents, and the m-PIMA™ Analyser.The m-PIMA™ test cartridges are supplied in boxes containing a product insert detailing instructions for sample collection as well as the test specific performance characteristics.

Before you are performing an m-PIMA™ test, carefully read the respective m-PIMA™ Cartridge Guide for details on sample application and cartridge handling.

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST

RUN TEST14:56

To start a test insert new cartridge and close door.

2019-11-07

Check correct date and time on your m-PIMA™ Analyser before running a test. Please refer to page 45 to learn more about how to change the time settings according to your local time zone.

• To initiate a test press the [RUN TEST] tile in the left upper corner of the «HOME» screen.

This will open the first «RUN TEST» screen and you are asked to insert a cartridge.

Your m-PIMA™ Analyser is designed to only process m-PIMA™ test cartridges. Do not insert any other cartridges, test strips or devices into the instrument.

4

24 4 RUNNING A TEST

How to insert an m-PIMA™ Test Cartridge

To insert a test cartridge you first need to manually slide the m-PIMA™ Analyser door to the left to get full access to the cartridge slot. Since the door will automatically close you need to hold it open while inserting the cartridge.

• Insert the cartridge in the direction indicated by an arrow on the cartridge label.

• Insert the cartridge in a slightly downward angle and push it beyond the catch until it is locked in place.

• Release the door which will then close by itself.

Upon inserting a m-PIMA™ test cartridge the internal sensors will detect its presence and initiate the test analysis sequence.

25

4


As a next step the m-PIMA™ Analyser reads the Data Matrix Code (DMC) on the cartridge label containing essential data for the performance of the test. The display screen changes briefly to «Reading cartridge» at this moment.

Once the m-PIMA™ Analyser has accepted the cartridge it will prompt you to enter both an Operator and a Sample ID. During data entry the test analysis continues in the background.

While it is not necessary to enter Operator and Sample ID immediately after the analysis has started, the m-PIMA™ Analyser will NOT display a result until you have entered the respective information.

How to enter an Operator

The «OPERATOR» screen opens showing a list with all archived Operators.You can choose an Operator directly from the Operator List or you can press the “New Operator” line to add a new entry.

You can enter an Operator of up to 16 characters.

• Confirm your choice or your entry, respectively, with i to proceed to the Sample ID entry. Any new Operator will be automatically added to the Operator List.

ELVIRA KLAWITTER

FIONA KUNZ

New Operator

LOTTE MUELLER

HENRY HONG

SAM MILLER

OPERATOR15:332019-11-07

RUN TEST15:33

Reading cartridge

2019-11-07

in progess

Note: Refer to page 42/43 for instructions on how to enter a new Operator into the Operator List when no test in running.

4

26 4 RUNNING A TEST

Your attempt to save an Operator which already exists in the Operator List will trigger the following Information screen.

• Press i to return to the Operator List.

The attempt to save an empty entry field will trigger the following Information screen.

• Press i to return to the Operator entry field.

Note: An isolated "Space" is not accepted as valid character.

INFORMATION15:33

Operator already exists.

2019-11-07

INFORMATION15:33

Select or enter Operator.

2019-11-07

27

4


How to enter a Sample ID

Once you entered an Operator the screen will automatically progress to the «SAMPLE ID» screen.

You can enter a Sample ID of up to 16 characters.

• Confirm your entry with i.

The attempt to save an empty entry field will trigger the following Information screen.

• Press i to return to the Sample ID entry field.

Note: An isolated "Space" is not accepted as valid character.

07-11-2019-ABCSAMPLE ID

15:332019-11-07

1 2 3 4 5 6 7 8 9 0

Q W E R T Y U I O P

A S D F G H J K L -

Z X C V B N M . _

#?+

INFORMATION15:33

Enter Sample ID.

2019-11-07

4

28 4 RUNNING A TEST


m-PIMA HIV-1/2 VL

Sample ID

07-11-2019-ABC

ANALYSIS14:562019-11-07

Analysis Completed

When the analysis is finished the m-PIMA™ Analyser prompts you to remove the cartridge.

Additionally an acoustic signal informs you about the completion of the test run.

• To remove the cartridge slide the m-PIMA™ Analyser door to the left and hold it. Press the catch so the locking mechanism will release and partly eject the cartridge. You have to manually remove the cartridge. Release the door which will then close by itself.

ANALYSIS14:562019-11-07

Test completed.Remove cartridge and close door.

• Discard the cartridge according to the institution’s standard operating procedures and local or national guidelines for biohazard waste disposal.

The result screen will not be displayed until the cartridge is removed.

All m-PIMA™ test cartridges are for single use only and must be discarded as biohazard waste after use.

Analysis in Progress (example)

After you successfully entered Operator and Sample ID, the «ANALYSIS» screen appears.

The display now shows the type of test, the ID of the sample currently analyzed and a progress bar with the estimated time to completion.

29

4


Printing Results immediately after Analysis

You may print an m-PIMA™ Test Report immediately after the test analysis is finished by pressing g.

If the USB Printer is not attached to the m-PIMA™ Analyser via one of the USB ports at the back of the instrument the print option is not enabled.

All results data is stored in the data archive. Go to the «HOME» screen by pressing e and select «ARCHIVE» to view archived results.

See further details on page 36 and 70.

Cartridge must not be removed by applying any force since this may lead to considerable damage of the m-PIMA™ Analyser! Follow the instructions given above or contact your local Technical Support for advice in case the cartridge got stuck in the instrument.

Once you removed the cartridge a m-PIMA™ Test Report will be automatically displayed, showing the test result and additional relevant test data (example shown below).

• Press w to view additional test related parameters.

• Press i to return to the initial «RUN TEST» screen and start a new analysis.

• Press e to continue with other menu options.

TEST REPORT2019-11-07 14:51

123456789-ABF

m-PIMA HIV-1/2 VL

Sample ID

07-11-2019-ABC

HIV-1 M/N

HIV-1 O

HIV-2

7425 cp/mL

Undetected

Undetected

Result No. 107

4

30 4 RUNNING A TEST

TEST REPORT15:33

Printing

2019-11-07

in progress

The «TEST REPORT» screen appears and a row of moving squares indicates the printing process.

Once printing is finished you will return to the «TEST REPORT» screen.

Test Report

m-PIMA HIV-1/2 VL


HIV-1 M/N

HIV-1 O

HIV-2

7425 cp/mL

Undetected

Undetected

Result No. 107



Signature


NAT-04000035

0.26.3


The m-PIMA™ Test Report (example)

The m-PIMA™ Test Report contains all information displayed on the result screen.

An example of a printed m-PIMA™ Test Report is shown to the right.

31

4


To change the Operator or Sample ID during analysis, press b in the «ANALYSIS» screen; this opens the «SAMPLE ID» screen again allowing you to change your previous Sample ID entry.

• Confirm your changes with i and the «ANALYSIS» screen will re-open.

If you want to change an Operator or enter a new Operator into the Operator List press b in the «SAMPLE ID» screen.

• Confirm Operator and Sample ID to return to the «ANALYSIS» screen.

Note: You can change your entries as long as the test run continuous. Once the analysis is finished changing of data entries is no longer possible.


m-PIMA HIV-1/2 VL

Sample ID

07-11-2019-ABC

ANALYSIS14:562019-11-07

During Analysis

During an active test run you can change the Operator and Sample ID or abort the current analysis.

How to Change Operator and Sample ID

07-11-2019-ABCSAMPLE ID

15:332019-11-07

1 2 3 4 5 6 7 8 9 0

Q W E R T Y U I O P

A S D F G H J K L -

Z X C V B N M . _

#?+

4

32 4 RUNNING A TEST

How to Abort an Analysis

If you need to abort an active analysis press c on the «ANALYSIS» screen.

The m-PIMA™ Analyser will ask you to confirm your decision.

• Press y to initiate the aborting procedure or press z to return to the «ANALYSIS» screen.

Abort current analysis?


YESNO

Note: m-PIMA™ test cartridges are single use devices and CANNOT be reused after you aborted an analysis.

The m-PIMA™ Analyser will prompt you to remove the cartridge (see details at “Analysis completed” on page 28).

ABORT ANALYSIS14:562019-11-07

Aborting completed.Remove cartridge and close door.

33

4


Thereafter the following error code will be displayed on the «TEST REPORT» screen.

• Press i to return to the initial «RUN TEST» screen and to start the next analysis.

• Press e to continue with other menu options.

• Press g to print an m-PIMA™ Test Report.

TEST REPORT2019-11-07 14:51

m-PIMA HIV-1/2 VL

Sample ID123400089-ABF

Result No. 123

Error Code 18006

5

34 5 ARCHIVE

5 ARCHIVE

All results stored in the Archive can be viewed, printed and exported or deleted. You can only access the Archive, if there is no analysis currently in progress. Up to 1000 test results can be stored in the m-PIMA™ Analyser archive.

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST

Sample ID# ViewDate

ARCHIVE2019-11-07 14:51

2019-11-06

2019-11-06 123456789-ABD-576123

12345-ABG-1232019-11-05

106

105

107 06-11-2019-ABC

123456789-ABF2019-11-05 75

89-FG2019-11-04 32

1-AH-352019-11-02 15

62-GU-12019-10-30 8

• To open the list with all results archived, press the [ARCHIVE] tile in the upper right corner of the «HOME» screen.

All available results are displayed in chronological order with the last result on top.

• Use the v and w keys to scroll the complete list.

• Press the header of column [#] or [Date] to reverse the chronological order of the results.

• Press the header of column [SAMPLE ID] to group results based on Sample ID.


5

View Results

• To view a result of interest, press f at the right end of the respective line. This will open the Test Report of this particular test run.

See page 29 for further options after opening the Test Report.

Select Results

Select your results of interest by pressing the specific lines in the result list. You will recognize marked results as highlighted in mint. Deselect a result by pressing the respective line once again.

Alternatively you can choose the «SELECT ALL» option in the Action Menu to select all results currently stored in the archive (see next page for details).

ARCHIVE14:51

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15

8

2019-11-06

89-FG

1-AH-35

62-GU-1

Sample ID# ViewDate

2019-11-06

2019-11-05

2019-11-05

2019-11-04

2019-11-02

2019-10-30

123456789-ABD-576123106

105

75

107 06-11-2019-ABC

2019-11-07

12345-ABG-123

123456789-ABF

ARCHIVE14:51

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15

8

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12345-ABG-123

123456789-ABF

89-FG

1-AH-35

62-GU-1

Sample ID# ViewDate

2019-11-06

2019-11-05

2019-11-05

2019-11-04

2019-11-02

2019-10-30

123456789-ABD-576123106

105

75

107 06-11-2019-ABC

2019-11-07

5

36 5 ARCHIVE

Note: Make sure you marked all results of interest before activating the printing process. If you miss to preselect the results of interest the «PRINT» option will remain inactive.

Should you attempt to press the respective menu line any way, an Information screen will be displayed informing you about the next steps to take.

SELECT ALL

EXPORT

DELETE

2019-11-06 123456789-ABD-576123

12345-ABG-1232019-11-05

PRINT

Sample ID# ViewDate

ARCHIVE2019-11-07 14:51

2019-11-06107 06-11-2019-ABC

106

105

INFORMATION15:33

Select result.

2019-11-07

Action Menu

Pressing h will open the Action Menu. Here you will find the respective action items and the «SELECT ALL» option.

Action Menu: Print

You need to attach the USB Printer to one of the USB ports of the instrument to print results from the archive.

• After selecting your results press h to select the «PRINT» option.

Note: If you did not attach the USB Printer the «PRINT» option remains inactive.


5

A «CONFIRMATION» screen appears.

• Confirm with y to print selected results from the archive. Press z to exit this screen and return to the result list where your previous choice will still be highlighted.

The printing activity is indicated by a row of moving squares.

Print 3 selected results?


YESNO

ARCHIVE15:33

Printing

2019-11-07

in progress

If you print more than one result the printing process can be aborted at any time this screen is shown.

The printed m-PIMA™ Test Report contains all information displayed on the result screen of the m-PIMA™ Analyser.

After successful print, the display automatically returns to the result list.

5

38 5 ARCHIVE

Action Menu: Export

You need to attach the respective export hardware (USB Storage Device, mobile modem, LAN cable) to the instrument to export results from the archive list.

Export Options

Export Hardware Details

Storage Device You can use FAT 32 formatted USB devices to export your result data in a CSV format (RFC4180) which can be opened with spreadsheet applications as Microsoft Excel.

Mobile Network Before you can use a mobile modem to send your data to a remote server the respective infrastructure needs to be established. Please contact your local distributor about available Connectivity options for the m-PIMA™ Analyser.Please also refer to the respective mobile modem product information.

Local Network (LAN)

The m-PIMA™ Analyser is equipped with a LAN port on the back of the instrument. If you want to transfer result data into a local network or via the CONNECT Universal Gateway (see page 9) make sure a respective LAN cable is connected and the m-PIMA™ Analyser is configured according to the local requirements.

Please contact your local distributor about available Connectivity options for your m-PIMA™ Analyser..


5

In case the data transfer medium is not recognized, the respective Export option will remain inactive.

• Select the results you want to export.

• Press h to select the «EXPORT» option.

Note: The Export option will remain inactive until you connect the respective Export hardware to the m-PIMA™ Analyser.

• Press «EXPORT» to open the «EXPORT MENU» and initialize the export option of your choice.

As a default option the export of data via USB Storage Device is available.

Depending on the configuration your m-PIMA™ Analyser can also provide data export via Mobile Network and/or to a Local Network and the CONNECT Universal Gateway, respectively.

EXPORT MENU14:56

Storage Device

Mobile Network

Local Network

2019-11-07

SELECT ALL

DELETE

2019-11-06 123456789-ABD-576123

12345-ABG-1232019-11-05

PRINT

Sample ID# ViewDate

ARCHIVE2019-11-07 14:51

2019-11-06107 06-11-2019-ABC

106

105

EXPORT

5

40 5 ARCHIVE

The exporting activity is indicated by a row of moving squares.

Exporting can be aborted at any time this screen is shown.

The screen to the right will inform you about the successful export of your data.

You can go back to the «HOME» screen or return to the result list by pressing i.

ARCHIVE15:33

Exporting

2019-11-07

in progress

ARCHIVE14:562019-11-07

Export completed.

Note: The storage medium does not need to be removed to continue, however, removal is recommended, especially when the m-PIMA™ Analyser operates on the integrated battery.


5

• Press h to select the «DELETE» option.

The m-PIMA™ Analyser will ask for your confirmation to proceed.

• Press either y to ultimately delete the selected results or z to exit this action and return to the result list.

Once you confirm with y the selected data will be deleted from the archive. All other results remain unchanged.

Note: Deleted results cannot be recovered.

Action Menu: Delete

If you want to delete results from the archive you can either select the results of interest by pressing the respective line or press «SELECT ALL» in the Action Menu. Selected results are highlighted in mint.

ARCHIVE14:51

32

15

8

2019-11-06

89-FG

1-AH-35

62-GU-1

Sample ID# ViewDate

2019-11-06

2019-11-05

2019-11-05

2019-11-04

2019-11-02

2019-10-30

123456789-ABD-576123106

105

75

107 06-11-2019-ABC

2019-11-07

12345-ABG-123

123456789-ABF

Delete 3 selected results?


YESNO

After successful deletion, the display automatically returns to the updated result list.

6

42 6 SETTINGS

6 SETTINGS

You can change the general settings of your m-PIMA™ Analyser.

• Press the [SETTINGS] tile in the lower left corner of the «HOME» screen.

A list of all available setting options is displayed.

Operator List

All Operator entries are saved and archived in the Operator List.

Here you can enter a new Operator or delete an already existing entry.

• Press «Operator List» to open the list.

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST

SETTINGS14:56

Date and Time

Language

Advanced Settings

2019-11-07

Operator List


6

Enter an Operator

• Select «New Operator» to open the keypad screen and enter a new Operator.

• Confirm with i to save the new Operator and to return to the now updated «OPERATOR LIST». Operators are displayed in alphabetical order with the last active Operator on top. Press b to return to the «OPERATOR LIST» without saving any changes.

New Operator

LOTTE MUELLER

OPERATOR LIST2019-11-07 14:51

+

ELVIRA KLAWITTER

FIONA KUNZ

HENRY HONG

SAM MILLER

PAUL GONZALES

NEW OPERATOR15:332019-11-07

1 2 3 4 5 6 7 8 9 0

Q W E R T Y U I O P

A S D F G H J K L -

Z X C V B N M . _

#?+

6

44 6 SETTINGS

Delete selected Operators?


YESNO

New Operator

LOTTE MUELLER

OPERATOR LIST2019-11-07 14:51

+

SAM MILLER

ELVIRA KLAWITTER

FIONA KUNZ

HENRY HONG

PAUL GONZALES

• To delete entries in the «OPERATOR LIST» select the entry of interest by pressing the respective line which will then be highlighted in mint.

• Press d and a Confirmation screen will open prompting you to actively confirm the deletion process.

• Select y to initiate the deletion process and to subsequently return to the «OPERATOR LIST». The selected entries are now ultimately deleted from the Operator List.

• Select z to cancel the deletion process and to return to the unchanged «OPERATOR LIST».

Delete an Operator

You can only delete an existing Operator when no analysis is running.


6

Date and Time

• If you want to adjust the time according to your local time zone press the respective line in the «SETTINGS» list.

Note: You can adjust time in a range of + 24:00 hours. As a consequence time adjustment may also lead to a change of date by + 1 day.

• Use the up and down arrows to adjust the numbers. Confirm with i to return to the «SETTINGS» list.

Press b to return to the «SETTINGS» list without saving any changes.

2019 11 07

Year Month Day

Hour Minute

14 56

DATE AND TIME14:562019-11-07

SETTINGS14:56

Operator List

Language

Advanced Settings

2019-11-07

Date and Time

6

46 6 SETTINGS

SETTINGS14:56

Operator List

Date and Time

Advanced Settings

2019-11-07

Language

• Press the «Language» line in the «SETTINGS» list. This opens a list with all available languages.

• Select the language of interest by pressing the respective language line.

Your selection is highlighted in mint.

• Press i and the m-PIMA™ Analyser will ask for an active confirmation.

Languages

The m-PIMA™ Analyser provides you with different language options for the User Interface. The default language setting is English.

LANGUAGE14:56

English

Deutsch

2019-11-07

Português

Español

Français


6

• Press y to change to your language of choice and to subsequently return to the «SETTINGS» list.

• To return directly to the «SETTINGS» list without saving any changes press z.

Advanced Settings

This sub menu provides you with additional setting options.

Change language to Français?


YESNO

SETTINGS14:56

Operator List

Date and Time

Language

2019-11-07

Advanced Settings

6

48 6 SETTINGS

Connectivity

Your m-PIMA™ Analyser is equipped to send result data from the archive to a remote server via Mobile Network.Furthermore you can send archive data to a local network or via the CONNECT Universal Gateway by connecting a LAN cable to the LAN port at the back of your m-PIMA™ Analyser.

All options available in the sub menus are only relevant in combination with the respective hardware.

For further information please refer to the respective product information or contact your local distributor.

Calibrate Screen

The screen of your m-PIMA™ Analyser was calibrated at manufacturing. To provide proper functionality and sensitivity of the keys an occasional recalibration of the screen may be advisable.

• Open this sub menu to activate the recalibration mode.

ADVANCED SETTINGS14:56

Calibrate Screen

Test Mode

Signal Tone

2019-11-07

Connectivity


Calibrate Screen

Test Mode

Signal Tone

2019-11-07

Connectivity


6

The m-PIMA™ Analyser will ask for an active confirmation at that point.

• Press y to open the calibration screen or press z to return to the «ADVANCED SETTINGS» list.

• Use a stub pen or the like and carefully press the centre of all calibration marks which will be displayed consecutively starting in the left upper corner.

Note: If you miss to consecutively press the calibration marks in a time period of 15 sec the calibration process will be canceled without saving any changes.

Calibrate screen?


YESNO

6

50 6 SETTINGS

Test Mode

The default Test Mode on your m-PIMA™ Analyser is called Regular Mode and allows for processing of m-PIMA™ test cartridges. As an additional option your m-PIMA™ Analyser can be operated in Demo Mode which provides you with a significantly shorter simulated test run for demonstration purposes. A Demo Mode run takes approx. 5 minutes.

• Choose «Test Mode» from the «ADVANCED SETTINGS» list to switch between Demo Mode and Regular Mode, respectively.

• Press the respective line which will then be highlighted in mint. Confirm your choice with i.


Calibrate Screen

Test Mode

Signal Tone

2019-11-07

Connectivity

TEST MODE14:56

Regular Mode

2019-11-07

Demo Mode


6

Switch to Demo Mode?


YESNO

Your m-PIMA™ Analyser will ask for an active confirmation before the change of Test Mode is initiated.

• Press y to continue or z to return to the «TEST MODE» screen without saving any changes.

Note: The m-PIMA™ Analyser will reboot to change the Test Modes. This may take a couple of minutes during which the screen will finally turn completely black for a while before the next screen is displayed.

After successful reboot your m-PIMA™ Analyser will display a respective warning screen.

• Press i to enter the «HOME» screen of the Demo Mode.

Demo Mode activated.

WARNING15:332019-11-07

DEMO

TEST MODE15:33

Switching Test Mode

2019-11-07

in progess

6

52 6 SETTINGS

While you are working in Demo Mode you will find the word “DEMO” as an indicator in the right corner of the header of every screen.

All options available in Regular Mode are also accessible in Demo Mode. Test results generated in Regular Mode are not visible in the Demo Mode archive, but will be restored upon return to Regular Mode.

Test Reports in Demo Mode resemble those in Regular Mode for the respective assay, though no diagnostic results are given (see example).

Your m-PIMA™ Analyser remains in Demo Mode until manually switched back to Regular Mode.

Note: With every switch from Demo to Regular Mode the Demo Archive and the Demo Operator List will be cleared.

TEST REPORT2019-11-07 14:51

DEMO

m-PIMA HIV-1/2 VLDemo


HIV-1 M/N

HIV-1 O

HIV-2

Demo

Demo

Demo

Result No. 123

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

DEMO

DEMO


6SIGNAL TONE

14:56

On

2019-11-07

O�


Calibrate Screen

Test Mode

Signal Tone

2019-11-07

Connectivity

Signal Tone

Your m-PIMA™ Analyser is equipped with acoustic signals to alert the operator of actions requested by the instrument.

• If you want to turn off certain acoustic signals press the respective line and choose “Off” on the following screen.

• Press i to confirm your choice and to return to the «ADVANCED SETTINGS» list.

Note: This option is only available with m-PIMA™ Analyser software version 0.24 or higher. As a default setting all acoustic signals are activated.

By turning off the Signal Tone the following signals will be deactivated:

a) signal alerting the operator of a successfully finished test run

b) signal indicating the insertion of a test cartridge before a test run has been properly initiated by pressing [RUN TEST]

The following acoustic signals are always activated, regardless of Signal Tone setting:

a) signal alerting the operator of a terminated test run, leading to an invalid result

b) signals associated with the Power Warning screens (see pages 67/68).

7

54 7 DEVICE

7 DEVICE

• To open a list with device related information and options press the [DEVICE] tile in the lower right corner of the «HOME» screen.

Device Info

The Device Info screen provides you with a quick overview of some important characteristics of your m-PIMA™ Analyser.

• Select «Device Info» from the «DEVICE» screen to view the status data of the m-PIMA™ Analyser.

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST

DEVICE14:56

Service Export

2019-11-07

Software Update

Device Info


7

Category Information

SN Serial Number of the m-PIMA™ Analyser

IP address Network address used by the m-PIMA™ Analyser

Software Software version installed on the m-PIMA™ Analyser

Total testsNumber of total test runs performed on this instrument

Battery status Approximate charging state of the internal battery

Atm pressure Atmospheric pressure measured in hPa

DEVICE INFO14:56

SN

Software

Total tests

2019-11-07

NAT-04000987

Battery status

Atm pressure

0.26.3

45

65%

1013 hPa

IP address 82.126.134.0

The following information can be obtained:

7

56 7 DEVICE

Service Export

The Service Export function assists Technical Support in trouble shooting the m-PIMA™ Analyser.

Detailed test data collected with every test run are provided for further examination in a separate Service Export Archive.

• Select «Service Export» to get access to different export options.

You can export data from the last 100 analyses.

• Select the results of interest by pressing the respective lines in the list. Marked results are highlighted in mint.

• To initiate the Service Export process press h. This sub-menu also provides you with options to select all results and all errors.

DEVICE14:562019-11-07

Software Update

Device Info

Service Export

Result# Date

2019-11-06

2019-11-06

2019-11-05

106

104

107 valid

SERVICE EXPORT ARCHIVE 2019-11-07 14:51

2019-11-05105

valid

valid

Error 23023

2019-11-05103 valid

2019-11-04102 valid

2019-11-04101 valid


7

Result# Date

SELECT ALL

2018-03-22

2018-03-22

2018-03-21

SELECT ALL ERRORS

EXPORT

106

75

107 valid

SERVICE EXPORT ARCHIVE2019-11-07 14:51

2018-03-22105

valid

valid

Error 23023

• Press «EXPORT» to send selected results to a previously connected storage device.

Note: Service Exports may take up to a couple of minutes, depending on the number of files needed to be exported and the USB storage device used.

Successful export will be indicated by the following screen.

For more information about exporting data please refer to “Action Menu: Export” on page 38.

SERVICE EXPORT ARCHIVE15:33

Exporting

2019-11-07

in progress

SERVICE EXPORT ARCHIVE14:56

Export completed.

2019-11-07

7

58 7 DEVICE

DEVICE14:56

Service Export

2019-11-07

Device Info

Software Update

Software Update

Individual software updates on the m-PIMA™ Analyser can be done via USB (storage device) or LAN connection (CONNECT Universal Gateway).

Software updates must only be installed in cooperation with qualified and authorized technical support personnel.

Further information about using the CONNECT Universal Gateway in the context of software updates can be found in the m-PIMA™ Analyser Annex document AN-03-UG-m-PIMA-01.


8

8 POWER OFF & STORAGE

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST

• If you want to turn off the m-PIMA™ Analyser, press the [POWER OFF] tile on the lower part of the «HOME» screen.

A «CONFIRMATION» screen will open.

• Press z to return to the «HOME» screen; confirm with y to initiate the final shut down sequence.

The following screen will indicate that the m-PIMA™ Analyser is shutting down. This may take up approximately one minute during which the power status light will be flashing (green LED, see page 15). After the shutdown sequence is completed, the m-PIMA™ Analyser will turn itself off, the screen will turn black and the power status light goes off.

It is recommended to throw the main power switch on the back of the instrument to position ( O ).

Power O�

Shut down the m-PIMA™ Analyser?


YESNO

POWER OFF15:33

Shutting down

2019-11-07

in progess

8

60 8 POWER OFF & STORAGE

If for any reason it is not possible to turn off the m-PIMA™ Analyser via the described route or it does not react to any input from the touch screen, press the grey Power On button on the front of the instrument until the screen turns black. This might take a couple of seconds. The power status light goes off indicating that your m-PIMA™ Analyser is now switched off. To restart the m-PIMA™ Analyser, press the grey Power On button again.To protect the internal battery from undesired discharge during transport or long term storage of the m-PIMA™ Analyser the instrument automatically reactivates the EP-mode of the internal battery every time it is powered off.

Note: If a controlled shut down is not possible and therefore the instrument is turned off by pressing the grey button the EP-mode for the internal battery is NOT being activated.

Deinstallation

To disconnect the power transformer pull back the outer sleeve of the plug. DO NOT pull on the cord. Follow instructions on the cable tag thoroughly (see below). Violation of the described workflow may cause serious damage to the instrument. Please note the information sign attached to the power transformer cable.

m-PIMA™ Analyser Storage and Recharge Intervals

If you want to store the m-PIMA™ Analyser for longer periods of time below 30°C connect it to mains A/C power and turn it on to recharge the battery at least once every 6 months. If long term storage temperatures exceed 30 °C, the recharge intervals may need to be considerably shorter.

Note: Never store the m-PIMA™ Analyser with an empty battery. Always fully recharge the battery before long term storage.

4109

83-A

I-A

lere

q-0

1-02


9

9 TECHNICAL SUPPORT & ERROR CODES

TEST REPORT2019-11-07 14:51

m-PIMA HIV-1/2 VL

Sample ID123400089-ABF

Result No. 123

Error Code 18006

The m-PIMA™ Analyser performs a series of checks to ensure that all steps of the analysis process are completed successfully.

Should one of these checks discover an error, the test will be aborted automatically and an error code displayed on the screen (an example is shown to the right).

Technical Support

For Technical Support please contact your local distributor or call the respective number for your region:

EuropeRussia & CIS

+44 161 483 5884 [email protected]

Africa +27 21 5315 999 [email protected]

Asia Pacific +61 7 3363 7166 [email protected]

India +91 11 45089400 [email protected]

Latin America+57 2 6618916 +57 2 6618797

[email protected]

9

62 9 TECHNICAL SUPPORT & ERROR CODES

Error Codes

On the following pages possible Error Codes are listed. Due to the complex nature of the m-PIMA™ Analyser testing system (including interactions between instrument, cartridge, user, sample and other factors) one Error Code might be triggered by different events. Note: All cartridges are for single use only and must not be reused!

Error Code Action

12002, 18005

No assay software available on this device for this cartridge type. Check cartridge type.Repeat test with valid cartridge.Contact your local distributor or your regional Technical Support if the error persists.

15004Analysis aborted due to controlled shut down.See pages 67/68 and recharge your m-PIMA™ Analyser.

18004, 18007DMC information not available. Check cartridge label for damage or marks.Repeat test with new cartridge.

18006Check cartridge expiry date. Check correct date on your m-PIMA™ Analyser.Repeat test with valid cartridge.

20001

Sudden loss of power. Connect your m-PIMA™ Analyser to external power source and check whether internal battery is charging (see page 16).Contact your local distributor or your regional Technical Support if battery is not charging.


9

Error Code Action

21111-21115, 21120

Make sure that the sample capillary is completely filled. Keep analyser door closed during test run.Repeat test with new cartridge.Contact your local distributor or your regional Technical Support if the error persists.

21501Repeat test with new cartridge.Make sure that the sample capillary is completely filled.

21502Too low atmospheric pressure. Do not continue with testing until you have reached altitudes that are within specifications.

21503Too high atmospheric pressure. Do not continue with testing until you have reached altitudes that are within specifications.

23020

Cartridge or sample related errors.Please refer to the test cartridge guides PI-m-PIMA-04 or PI-m-PIMA-05 for further information about sample storage and handling.

23028

Unexpected amplification curve, e.g. due to individual sample properties.Repeat test with new cartridge.Contact your local distributor or your regional Technical Support if the error persists.

9

64 9 TECHNICAL SUPPORT & ERROR CODES

Error Code Action

23021-23205, 23207/23208, 23211, 23213-23216

Cartridge related errors. Repeat test with new cartridge.Contact your local distributor or your regional Technical Support if the error persists.

23212, 23217, 23026Repeat test with new cartridge.Contact your local distributor or your regional Technical Support if the error persists.

23206/ 23210

Check for correct cartridge insertion.Repeat test with new cartridge.Contact your local distributor or your regional Technical Support if the error persists.

52005Repeat test with new cartridge.Contact your local distributor or your regional Technical Support if the error persists.

53004Analysis aborted by Operator. No further action required.

60001, 60002, 60003Invalid system set-up. Contact your local distributor or your regional Technical Support.

10004, 10006, 10007, 18001, 18003, 21401, 21402, 21601-21603, 21999, 24004, 24005, 51773, 51788, 51789, 52008, 52010, 58040-58048, 58072-58084, 58102-58202, 58240-58344, 58349-58359, 58560, 58561, 58994

Contact your local distributor or your regional Technical Support.


9

Error Code Action

10002, 10003, 12000, 15000-15003, 18002, 18008, 18009, 18013, 21001-21305, 21403, 21404, 30001, 51015, 51016, 51272-51274, 51307, 51512-51772, 51774-51781, 51790-52007, 52009, 52011-58039, 58050-58071, 58100, 58101, 58220-58231, 58346, 58550, 58992, 58993, 58996

Check if a cartridge is still inserted in your m-PIMA™ Analyser. Remove cartridge. If the error persists restart your m-PIMA™ Analyser. Contact your local distributor or your regional Technical Support if the error persists.

20001-20003, 23209, 24001, 24002, 24006-24305

Repeat test with new cartridge.If the error persists restart your m-PIMA™ Analyser. Contact your local distributor or your regional Technical Support if the error persists.

12001, 18010-18012, 19001, 19002, 51021, 51256, 51286, 51287, 51291, 51308, 51356-51358, 58400-58402, 58500- 58510, 58990, 58991, 58995

Restart your m-PIMA™ Analyser. Contact your local distributor or your regional Technical Support if the error persists.

10

66 10 WARNINGS & ERROR MESSAGES

10 WARNINGS & ERROR MESSAGES

INFORMATION15:33

The m-PIMA™ Analyser archive is full.

Clear archive to proceed with testing.

2019-11-07

POWER OFF

HOME2019-11-07 14:51

ARCHIVE

SETTINGS DEVICE

RUN TEST

Archive Information

If the storage capacity of the archive is reached, no further analyses can be performed by the m-PIMA™ Analyser.

The [RUN TEST] tile on the «HOME» screen will remain inactive until the archive was cleared.

Pressing the inactive [RUN TEST] tile results in the following Information screen.

Make sure to save, download or export all required data before you delete results from your m-PIMA™ Analyser archive.

Even if the storage capacity of the archive is reached and therefore no analysis can be run, the remaining menu functions are still available.

67

10


Power Warnings

This Warning can appear at any time, also during an active analysis indicating that the m-PIMA™ Analyser is now running on its internal battery.At this point the instrument is fully functional and ongoing activities can be continued.As long as your m-PIMA™ Analyser is powered by the internal battery the battery symbol will be displayed in the status line of every screen (see also page 21).

• Press i to confirm the change of power supply mode and to return to the previous screen.

We recommend connecting the m-PIMA™ Analyser to A/C power as soon as possible.

When the following Warning is displayed the internal battery of your m-PIMA™ Analyser is almost empty. It may appear at any time while the instrument is running on battery power.

Connect the m-PIMA™ Analyser to A/C power immediately.

Menu functions are still active at this point.We recommend to finish all ongoing processes and to shut down the instrument.

The m-PIMA™ Analyser runs on internal battery.

Connect to A/C power.

WARNING15:332019-11-07

Internal battery low.

Connect to A/C power immediately.

WARNING15:332019-11-07

• Completely recharge the internal battery before you continue to work with the m-PIMA™ Analyser.

• Press i to return to the previous screen.

10


To prevent your m-PIMA™ Analyser from being damaged due to a sudden and uncontrolled power cut a controlled shut down process will be initiated automatically which puts the internal battery into its EP-mode when a critical low limit is reached (please refer to page 13 to learn how to deactivate the EP-mode).Note: Independent from current processes the

m-PIMA™ Analyser will stop all activities and turn itself off, even during an ongoing test run!

• Remove cartridge and connect your m-PIMA™ Analyser to A/C power to completely recharge the internal battery before you continue to work with the m-PIMA™ Analyser.

Export Errors

If the «EXPORT FAILED» screen appears, an unspecified error has occurred during the export of results. This may have been caused by either the storage device or the m-PIMA™ Analyser.

• Press i and repeat the export of results. Should this fail a second time insert a different USB storage device and export results. Should this error appear when using a Mobile Modem press i and repeat the export of results.

Controlled shutdown initiated.

WARNING15:332019-11-07

ERROR15:33

EXPORT FAILED

2019-11-07

Please also refer to the respective product information for further details and options.

69

10


If during export the storage device is removed from the USB port, the following screen appears.

• Press i and re-insert the storage device and attempt to export again.

If during export the storage capacity of the storage device is reached, the following screen appears.

• Press i and remove the storage device. Insert another storage device with adequate storage capacity and repeat export.

ERROR15:33

STORAGE DEVICE FULL.

2019-11-07

ERROR15:33

STORAGE DEVICE LOST.

2019-11-07

10


Insert new paper roll.

WARNING15:332019-11-07

Printer Warning

Should the USB Printer run out of paper, the following screen is displayed.

• After a new roll of paper has been inserted, confirm continuation of printing with i.

In case the error occurred during printing of an m-PIMA™ Test Report, the last report will be printed again.

For more information on the USB Printer, please refer also to the USB Printer User Guide.

Printer Error

If the «PRINTING FAILED» screen appears, an unspecified error has occurred during printing of m-PIMA™ Test Reports. This may have been caused by either the Printer or the m-PIMA™ Analyser.

• Press i and repeat printing.

Should the error persist contact your local Technical Support.

ERROR15:33

PRINTING FAILED

2019-11-07

71

10


Printed on 100% recycled paper.

Version 09UG-m-PIMA-01-09-EN

Revision date: 28-Jan-2020

Abbott Rapid Diagnostics Jena GmbHOrlaweg 1D-07743 Jena, Germanywww.abbott.com/poct

© 2020 Abbott. All rights reserved.

All trademarks referenced are trademarks of either the Abbott group of companies or their respective owners.

Documents

WHO Prequalification of In Vitro Diagnostics PUBLIC REPORT