WHO product testing round 3 · WHO/TDR-FIND Malaria Product Testing Programme – Round 3 3 Conditions for testing of products as part of the WHO/TDR-FIND Malaria Diagnostics Product

WHO product testing round 3

WHO-FIND Malaria RDT Evaluation Programme

WHO, with the Foundation for Innovative New Diagnostics

(FIND), is coordinating the development of a global specimen

bank of cryo-preserved malaria parasite samples to support

product testing (comparative performance evaluation of

commercially-available antigen-detecting malaria rapid

diagnostic tests – RDTs). The second round of testing

commenced in April 2009 at the Malaria Branch, Division of

Parasitic Diseases, United States Centers for Disease Control

and Prevention (CDC) and results were reported in April 2010.

The expression for interest for Round 3 of the Product Testing

Programme was released in October 2010.

An outline of the testing programme (Methods manual for

product testing of malaria rapid diagnostic tests, v3) and

notices to manufacturers concerning round 3 of product testing

are outlined below.

This document compiles all the steps followed during this

process with all related letters, documents and supporting

materials.

For more information concerning the other rounds, please see:

Round 1 | Round 2 | Round 4 | Round 5

For more information on the WHO-FIND Malaria RDT Evaluation

Programme, please see:

http://www.who.int/malaria/areas/diagnosis/rapid-diagnostic-tests

http://www.who.int/malaria/areas/diagnosis/rapid-diagnostic-tests

http://www.who.int/malaria/areas/diagnosis/rapid-diagnostic-tests/archive-who-product-testing-round1.pdf




WHO product testing round 3 – WHO-FIND Malaria RDT Evaluation Programme (documentation archive) | 2

19 October 2009 – Seeking expression of interest in participating in the WHO/TDR-

FIND malaria RDT product testing programme

1. Letter 1 to manufacturers

2. Attachments

Annex 1: General information on programme and timeline

Annex 2: Definition on production ‘lot’

Annex 3: Information on internal heat stability protocol

Appendix A: Expression of interest (EOI)

Appendix B: Material transfer agreement/confidentiality agreement (for

information only – do not fill out now)

Appendix C: Products to be included for evaluation (for information only –

do not fill out now)

Appendix D: Joint-submission or joint listing of products

10 December 2009 – Acceptance of EOI in WHO/TDR-FIND malaria RDT product

testing programme: Round 3

1. Letter 2 to manufacturers

2. Attachments

Annex 1: Order form; “Manufacturers’ panel” – culture-derived

P. falciparum samples

31 January 2010 – Acceptance of application into WHO/TDR-FIND malaria RDT

product testing programme: Round 3 and other information

1. Letter 3A to manufacturers

2. Attachments

Annex 1: Products to be included for evaluation

Annex 2: Order form; “Manufacturers’ panel” – culture-derived


Annex 3: Information pack on manufacturing site stability testing

22 February 2010 – Confirmation of the final list of products for WHO/TDR-FIND

malaria RDT product testing programme: Round 3 and other information

1. Letter 3B to manufacturers

2. Attachments

Annex 1 (1): Availability of panels of cultured P. falciparum parasites for

preliminary testing of products by manufacturers (optional)

Annex 1 (2): Order form; “Manufacturers’ panel” – culture-derived


Annex 2: Temperature monitor envelope and information needed

WHO product testing round 3 – WHO-FIND Malaria RDT Evaluation Programme (documentation archive) | 3

Annex 3: Information pack on manufacturing site stability testing

Annex 4: SOPs for transportation of products to US CDC

31 March 2010 – Deadline for shipment of RDTs to US CDC

4 May 2010 – Final list of products accepted into round 3 of WHO/TDR-FIND malaria

RDT product testing programme

Round 3 product summary list

29 August 2011 – Characteristics of evaluation panel used in round 3

11 October 2011 – Results of WHO malaria RDT product testing round 3 (2010-2011)

Malaria Rapid Diagnostic Test Performance – Results of WHO product testing of

malaria RDTs: Round 3 (2010–2011)

Malaria rapid diagnostic test performance : summary results of WHO malaria RDTs

product testing: rounds 1–3 [2008–2011]

Interactive RDT performance guide

Interactive programme to assist in the selection of malaria RDTs based on the

performance in the WHO product testing rounds 1–3, located on the FIND website

16 December 2011 – Performance des tests de diagnostic rapide du paludisme

Bilan des résultats d’évaluation des produits par l’OMS : Séries 1–3 (2008–2011)

20 December 2011

WHO information note on recommended selection criteria for procurement of malaria

rapid diagnostic tests (RDTs)

http://who.int/malaria/publications/atoz/9789241502566/en/

http://apps.who.int/iris/bitstream/10665/70792/1/TDR_RDT_11.1_eng.pdf

http://www.finddiagnostics.org/programs/malaria-afs/malaria/rdt_quality_control/product_testing/malaria-rdt-product-testing/index.jsp

http://who.int/malaria/publications/atoz/9789241502566/fr/

WHO/TDR-FIND Malaria Product Testing Programme – Round 3

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ANNEX 1

ROUND THREE OF WHO/TDR-FIND MALARIA RDT PRODUCT TESTING PROGRAMME

This document includes details of Round Three of WHO/TDR-FIND Malaria Rapid Diagnostic Test (RDT) Product Testing Programme and criteria for inclusion of products.

The only action necessary at present for a manufacturer interested in participating in this Programme is to send the details of the products considered for submission to WHO/TDR-FIND Round Three Product Testing Programme, in accordance with the instructions described below. Such an Expression of Interest will not be binding on either party, but must be received by FIND by 30 November 2009 to allow participation in the Third Round of testing (which is scheduled to commence at the end of March of 2010).

A. Introduction

WHO is proposing to undertake this evaluation to assess the performance of antigen-detecting malaria rapid diagnostic tests (RDT). All product testing will be conducted at the Malaria Branch, Division of Parasitic Diseases, and Centers for Disease Control and Prevention, Atlanta, U.S.A. with an additional stability assessment performed at the site of manufacturer. The Programme will be coordinated jointly by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (WHO/TDR), and the Foundation for Innovative New Diagnostics (FIND).

Testing will be conducted in two phases. A total of 2200 Malaria RDTs, consisting of 1100 tests from each of the two separate lots for each product, will be required to be submitted for the Programme, Phase I of the testing process will be performed against a panel of cryo-preserved preparations of cultured parasites and recombinant antigens. Phase II will be performed against a panel containing diluted cryo-preserved preparations of wild parasites, and parasite-negative samples. Manufacturers cover the courier cost and associated costs of transport of RDTs to US CDC and the cost of transport of proficiency panels from CDC to the site of manufacturer.

A subset of the product test panel prepared from cultured P. falciparum malaria parasites will be made available to manufacturers for their own quality control testing prior to submission of products to the Product Testing Programme (optional), and for a stability test at the manufacturing site required later (mandatory) as part of the Product Testing Programme.

Submission of a request for inclusion of products (Expression of Interest, EOI) in the Third Round of testing will close 30 November 2009. Only these products listed on the Appendix A will be eligible for Round Three of the Product Testing Programme. WHO reserves the right to limit the number of products per manufacturer if the total number of products in the EOI is beyond the capacity for testing by the Programme in a single round of Product Testing.

As with the first and second rounds of Product Testing, Round Three of WHO/TDR-FIND Malaria RDT Product Testing Programme the performance data will form the basis of procurement recommendations of WHO and the WHO tendering programme. RDTs must be submitted to the Product Testing Programme will be listed on the WHO web site.

Data on product performance during testing will be published by WHO/TDR-FIND as an addition to the published results of each Round of Product Testing and will guide future procurement of RDTs by WHO, other UN Agencies and national health authorities. Manufacturers will be informed of the performance results, in accordance with the terms of the attached sample Confidentiality Agreement. (The Confidentiality Agreement in APPENDIX B should not be signed at this stage, but will be required at the time of final product submission for the WHO/TDR-FIND Product Testing Programme – see diagram on page 6).


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It is not necessary to re-submit a product to subsequent rounds for the product to remain eligible for WHO procurement, or to have its performance listed on the WHO website. However, a manufacturer may resubmit a product to subsequent rounds. Note that the results of earlier rounds will be replaced in the performance report by results of subsequent rounds to which the product is submitted.

WHO will list all products evaluated as part of the WHO/TDR-FIND Malaria RDT Product Testing Programme together with their performance data on a dedicated page of the WHO website and in a hard copy publication. WHO may remove a product from the website list or require re-submission of a product for performance testing if changes in product specifications listed in ANNEX 2 indicate that the RDT should be considered a new product, or performance data obtained from lot testing in the field are considered to be consistently outside those of the product testing programme published by WHO and/or FIND. The manufacturer of a listed product of which the product specifications have been changed, is required to inform WHO and FIND of such changes prior to the commercial release of the changed product. Publication of data on product performance and/or inclusion in the above mentioned website list does not guarantee that the RDTs in question will actually be procured by WHO or any other party. Participation in the Product Testing Programme, publication by WHO/TDR-FIND of the testing results and/or inclusion in the website list may not be used by the manufacturers and suppliers concerned for commercial or promotional purposes. With respect to the manufacturers' or suppliers' participation in the Product Testing Programme, under no circumstances is a manufacturer or supplier authorized to refer to WHO and/or FIND, the publication of the testing results by WHO and/or FIND and/or inclusion in the website list, in any statement or material of an advertising or promotional nature, press release and/or similar public statement and/or other material aimed at promoting the manufacturer or supplier and/or its products.

Furthermore, publication of the testing results and/or inclusion in the website list does not in any way imply an endorsement, certification, warranty of fitness or recommendation by WHO or FIND of any company or product for any purpose, and does not imply preference over products of a similar nature that are not mentioned. Neither WHO or FIND will accept any liability or responsibility whatsoever for any injury, death, loss, damage, or other prejudice of any kind that may arise as a result of, or in connection with the procurement, distribution and use of any product, as to which WHO and/or FIND has published the testing results and/or which is included on the list.

B. Criteria for entry to the Product Testing Programme

Conditions of entry are derived from the recommendations of WHO expert consultations at Geneva, Kisumu and Atlanta in 2006.


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Conditions for testing of products as part of the WHO/TDR-FIND Malaria Diagnostics Product Testing Programme

1 (see Diagram on page 6)

1. By 30 November 2009: Submission of an Expression of Interest (EOI) to FIND (as in the attached Appendix A).

Documents to be submitted by E-mail and hard copy to:

Julie Vercruysse FIND Foundation for Innovative New Diagnostics 16 Avenue de Budé 1202 Geneva Switzerland Tel: +41 (22) 710 05 97 Fax: +41 (22) 710 05 99 E-mail: [email protected] With a copy to [email protected]

2. By 15 January 2010 (if EOI is accepted): Fulfillments of the requirements for taking part in

Round 3 of Product Testing Programme including:

a) Current ISO 13485:2003 (By E-mail)

b) Provision of an acceptable heat stability protocol of internal quality assurance (ANNEX 3). (By E-mail)

(Manufacturers who already fulfil these criteria and participated in the First Round of WHO RDT Product Testing and included in the WHO RDT website (http://www.wpro.who.int/sites/rdt) under list of commercially available malaria RDTs, are not required to submit further evidence concerning this).

c) Submission of 2 original copies of the Confidentiality Agreement (APPENDIX B) and acceptance of conditions for product testing and publication of results, including the undertaking to perform a stability test of submitted product lots according to a protocol specified by WHO-FIND and to submit the results thereof to WHO-FIND for publication

2 (By

hard copy and E-mail)

c) Final Product List (APPENDIX C) and product leaflets (By hard copy and E-mail)

3. By End of March 2010: Free supply and delivery of Malaria RDTs to US CDC, Atlanta. (see point E below)

4. Re-labelled products that are manufactured at the same site and under the same conditions as a

tested product, and fulfills the criteria in APPENDIX D may be jointly listed with the tested product under the criteria and conditions listed in APPENDIX D.

5. The above actions should be undertaken if and when WHO or FIND so notifies the

manufacturer. No product testing will take place unless the manufacturer has fulfilled the above conditions by the dates set by WHO and FIND and in accordance with WHO and FIND's instructions.

1 It is planned to include a product specific audit as a criteria in the future, through a mechanism to be determined by WHO

2 The format of the stability test outlined in : WHO (2006) Towards Quality testing of malaria rapid diagnostic tests: Evidence and

methods, Manila, WHO


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D. Supply of products for testing

• A total of 2200 tests consisting of 1100 tests from each of the two separate lots must be submitted for the Programme. .

• All RDTs must be received at US CDC by a given deadline (not before middle of March 2010) in order to be accepted for product testing. (Temperature monitors for the duration of the transportation can be obtained from FIND free of charge at request)

• All products will be stored in an air conditioned, temperature monitored room from the time of receipt until the actual testing occurs (the product testing site will determine the order in which testing will be conducted)

• Sufficient product of each lot should be provided (as mentioned) to conduct both phases of testing against the challenge panel (Towards quality testing of malaria rapid diagnostic tests: Evidence and methods. Manila, World Health Organization, 2006). If a product does not display sufficient performance against the Phase 1 panel, the lot will not be tested against the Phase 2 panel. Sufficient performance is defined as > 80% detection rate at 2000 parasites/µl.

Important note on RDT format

Manufacturers may submit products in any format and for any target antigen. RDTs with the same product name but different format (e.g. cassette and dipstick) are considered as separate products and will require separate submission and testing. On publication of the testing results by WHO-FIND, the introductory text accompanying the table of product performance characteristics will emphasize the current WHO recommendation that cassettes are preferred to dipsticks for field use in endemic countries. Manufacturers are therefore advised to consider submitting only tests in cassette format.

It is noted that Rounds 1 and 2 of Product Testing (2007-2008) included few products targeting P. falciparum specific pLDH. These products may have advantages in certain endemic settings and therefore, we encourage manufacturers to seriously consider submission of such products.

E. Oversight: Specimen Bank Review Committee

The Malaria Specimen Bank (currently at US CDC), is the repository of characterized samples against which product testing will occur, and includes recombinant antigen, culture-derived and wild-type malaria parasites, and negative samples. The wild-type parasites are collected from a geographically-diverse network of collection sites in Asia, Africa and South America, and prepared according to standard protocols.

A Specimen Bank Review Committee will oversee the technical and logistical aspects of the testing and evaluation process, including the development of Standard Operating Procedures (SOPs), oversight of ethical approval for the collection sites contributing to the Specimen Bank (including submission to the WHO Ethics Committee, and local ethical review board) and oversight of the product testing and reporting of results.

Terms of Reference of the Specimen Bank Review Committee:

The Malaria RDT Specimen Bank Review Committee will provide recommendations to WHO and FIND on:

• Development and modifications of SOPs for specimen collection and use

• Accumulation and content of the Specimen Bank, and characterization and maintenance

• Policy on access to the Specimen Bank


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• Protocols for laboratory-based testing of the accuracy and stability of malaria RDTs, including product testing and lot testing

• Interpretation of the results of product testing, prior to publication.

Composition

Core: WHO/TDR [1

3],

Foundation for Innovative New Diagnostics (FIND), [3] US Centers for Disease Control and Prevention (CDC), [2] Médecins sans Frontières, [1] Collection sites: 1 African, [1] 1 non-African, [1] Specimen characterization centers:

Hospital for Tropical Disease, UK [1] Army Malaria Institute, AU, [1]

3 Figure in brackets indicates the number of representatives.


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WHO/TDR-FIND Malaria RDT Product Testing

Programme

Step 1: Submission of Expression of Interest (Appendix A)

Step 2: FIND sends EOI Acceptance letter to manufacturers, final number

of tests per manufacturers that can be submitted to Round 3 and details for obtaining the optional culture panel from CDC for manufacturer quality control testing.

Step 3: Submission of ISO 13485:2003 and Provision of heat stability

protocol of internal quality assurance (If not already submitted previously), TWO signed ORIGINAL copies of Confidentiality Agreements (APPENDIX B), Final list of products (APPENDIX C), and Product inserts/leaflets for each product submitted. Request for Temperature monitor for duration of RDT transportation (Optional)

Step 4: Review of the submissions by Steering committee

Step 8: Applicant submits results of the stability test performed at the

manufacturer site every 3 monthly until the end of the specified shelf life

Step 5: FIND sends Confirmation of acceptance of Final list of products for

the Product Testing Programme

Step 6: Applicant submits a total of 2200 tests consisting of 1100 tests from

each of two separate lots to US CDC

Step 7: Applicant obtaining parasite specimen samples from US CDC for

the stability testing at manufacturer site

Step 9: Results of the Product Testing Programme at US CDC will be

available

Deadline for Receipt

30 NOV 2009

Deadline for Receipt 15 JAN 2010

Deadline for Receipt END of MAR

2010

07 DEC 2009

JAN 2010

JAN 2010

MAR/APR 2010

February 2011


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F. Further Information

Further information on the Product Testing Programme can be found in:

1. Rapid Diagnostic Tests for Malaria: Methods Manual for Laboratory Quality Control Testing Version 5, Aug 2008, Manila, World Health Organization – Regional Office for the Western Pacific.

2. WHO (2006B). Towards quality testing of malaria rapid diagnostic tests: Evidence and methods, Manila, World Health Organization.

3. Initiative for Quality Assurance of Malaria Rapid Diagnostic Tests: Outline of Product Testing and associated protocols, 2007. (Product testing Overview)

4. Methods Manual for Product Testing of Malaria Rapid Diagnostics Tests, Version 1 (Web Version), April 2008, WHO.

All the above documents can be found at: http://www.wpro.who.int/sites/rdt/documents/list.htm www.finddiagnostics.org and www.who.int/tdr or can be obtained by sending an email to: [email protected]


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ANNEX 2

Definition of a 'Product' and 'Lot' It is necessary to clearly define the terms “product” and “lot” to implement the proposed testing scheme, as product testing results should be applied only to a specifically defined and labelled product, and lot testing results should be applied only to a clearly defined and labelled lot.

(1) Lot. The definition of a “lot” is the responsibility of the manufacturer. All manufacturers must have current ISO 13485:2003 or US FDA 21 CFR 820 certification and an appropriate “lot” definition must be compatible with this.

(2) Product. Defining a malaria RDT “product” for the purposes of a product testing scheme is more difficult. However, this definition should be based on consistency in overall design and on the major constituents of the RDT that are likely to have a significant impact on RDT stability and accuracy. Assuming that evidence of equivalent performance can be provided, the following applies:

a) Similar but re-labelled products from various manufacturers should generally be considered different products (see joint listing of products below) but may be considered the same product if specifically indicated by the manufacturers concerned.

b) Monoclonal antibodies (Mab) – A change in target epitope, or of the species from which target antigen for Mab development is derived, should constitute a new product. A change in source (manufacturer) or modifying the amount of Mab used in a test would not constitute a new product if the Mab cell line originated from the same source.

c) Dye conjugate (signal reagent) – A change in specification or type of label (e.g. colloidal gold, latex particle or liposome) should constitute a new product, but a change in manufacturer/source should not.

d) Format – A change in assay presentation between, for example, a dipstick, cassette or card, constitutes a new product.

e) Buffer – A change in assay buffer constituents or pH does not constitute a new product.

(3) Equivalence of performance. Where changes made have the potential to significantly affect accuracy of the RDT, including changes in raw materials or components, including Mabs, signal reagents, buffers, nitrocellulose membranes, or in cassette design, equivalence of performance data should be provided to WHO-FIND to demonstrate that the modified product has a performance equivalent to, or better than, that previously submitted to formal testing. As this is an activity that should be performed as part of routine internal QA by the manufacturer, demonstration and notification of equivalence should not result in additional costs or workload.

Reference:

1. Towards Quality Testing of Malaria RDT-Evidence and Methods, 2006, World Health Organization


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ANNEX 3

Internal Heat Stability Protocol at manufacturing site

As evidence of stability testing, WHO-FIND will accept protocols submitted by manufacturers that comply with the points listed below. By providing WHO-FIND with the required evidence of testing for product storage temperature and shelf life, and confirmation that products have been tested according to these protocols, the manufacturer automatically confirms that WHO-FIND shall be entitled to disclose such evidence.

The following standards for stability testing are modified from Hornback, L.A., originally published in IVD Technology, April 2004 (See references)

A stability study for in-vitro diagnostic device (IVD) reagents has the same elements as those dictated for stability testing of drugs including the following:

• A written stability testing programme designed to assess the stability characteristics of IVDs.

• A stability protocol with predefined acceptance criteria that can be correlated to the label claims.

• Testing multiple unique product lots. A stability study is required to use three product lots that are manufactured when the manufacturing process has been well defined and can be consistently executed.

• Evaluation of each stability attribute via a statistically valid sample size and testing intervals. The sample size should be sufficient to overcome the precision of the test method used, considering the cumulative effect of all elements of the test system (i.e., individual reagents and instruments). The test intervals should be chosen so that trends may be discerned from variability of the data. At a minimum, stability testing should continue to one time interval past labeled expiration.

• Control of material storage. For real-time stability testing, the IVD reagents should be stored under the conditions stated on the label (e.g., temperature, humidity, light protection).

• Testing IVD in the same container-closure system as the marketed product.

• Use of reliable, meaningful and specific test methods.

The requirement set forth in the last bullet point implies the use of blood samples containing adequate parasite antigen to produce a clear test line on the RDT near the minimum equivalent parasite density that the RDT is expected to detect.

Use of Accelerated Study Data

Accelerated stability studies are useful for predicting the shelf life of IVD. Such accelerated studies subject IVD to extreme conditions—typically elevated temperatures—to the extent that the device endures significant and measurable deterioration during the testing period. Mathematical extrapolations, such as the Arrhenius equation, are then used to calculate the predicted shelf life of the IVD. However, not all IVD follow a predictable degradation rate. Some products will perform acceptably until they fail, in which case only real-time testing will suffice.

According to the United States Food and Drug Administration's Office of In Vitro Diagnostic Device Evaluation and Safety, accelerated stability studies are acceptable in the following situations:

• establishing preliminary claims in new products only if there is sufficient correlation to an existing

product and, • supporting implementation of a change to an existing product.

The European standard EN 13640:2000 provides guidance on not only conducting real-time and accelerated stability studies but also making calculations using the Arrhenius equation. Only real-time


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stability data are acceptable for testing of either newly licensed IVD or major changes to existing IVD, but for purposes of malaria RDTs it is recognized by WHO that accelerated data, used with reference to accelerated and real-time data from pre-existing products, is acceptable as an interim measure.

References

1. Hornback, L. A. Stability testing for IVDs. IVD Technology 10 (2004).


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APPENDIX A: Expression of Interest – Notification of interest to submit an antigen- detecting malaria rapid diagnostic test to the WHO/TDR-FIND Malaria RDT Product

Testing Programme

1. P: falciparum, V: vivax, O: ovale, M: malariae, Pan: all. 2.'Dipstick' refers to simple nitrocellulose strip which requires placement in well. Cassette / card indicates strip enclosed in (plastic) cassette or card.

Signature_______________________ Name _____________________________ Designation / position _________________________

Company name Product Name Catalogue Number

Plasmodium species

targeted1

Target antigen(s) Format2

Dipstick: D Cassette: Ca

Card: Cd

Packaging (Individual or bulk).

Number of tests per box

All materials can be included?

(lancets, swabs, wells if required)

A

B

C

D

E

Product name Shelf life Storage temperature recommended by

manufacturer

Temperature stability data on which shelf-life is based

('Accelerated' or 'Real time')

Contact person (If appropriate)

Address (for procuring tests)

Email URL

Contact numbers

A

B

C

D

E


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NOTES:

• Please note that the information submitted on this form should be accurate for WHO-FIND publication purposes

• This Expression of Interest should be submitted to Julie Vercruysse, 16 Avenue de Budé, 1202 Geneva, Switzerland, Email: [email protected], with an e-copy to: [email protected], by 30 November 2008.

• Manufacturers should ensure that receipt is acknowledged. The provision of the required product details in this table, and the provision of evidence demonstrating compliance with the requirements set forth in Annex 1 point C, is necessary in order for the products to be considered by WHO for inclusion in the initial round of Product Testing.

• Only products listed above maybe included in the list of products finally submitted to the Product Testing Programme. WHO-FIND reserves the right to limit the maximum number of products that can be submitted by manufacturers, if the listed products in the EOI is beyond the capacity for testing by the Programme in a single round of Product Testing. Manufacturer will be notified accordingly.

• If co-listing any product, Appendix D must also be completed and submitted with the EOI.

• FIND will notify a manufacturer if and when products have been accepted for this round of Product Testing Programme.

• The submission of an EOI and/or the aforesaid evidence will neither obligate WHO-FIND to accept, nor obligate the manufacturer to actually provide, the listed products for product testing.

CHECKLIST for manufacturer before Submission of EOI 1. ISO 13485:2003 Certificate (can be submitted by 15 Jan 2010) 2. Heat Stability Protocol (can be submitted by 15 Jan 2010) 3. Completed and signed product specifics (Appendix A) – 30 Nov 2009 4. Completed and signed Co-listing details (if relevant) (Appendix D) - 30 Nov 2009 (signed by both the manufacturer and the owner of the product)


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APPENDIX B

WHO STANDARD CONFIDENTIALITY AND MATERIAL TRANSFER AGREEMENT

Between

.........................................................having its principal offices at......................................................................

.........................................................(hereinafter referred to as "the Company");

and

The World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland, (hereinafter referred to as

“WHO”).

The Company has developed (a) rapid malaria diagnostic test(s), known under the trademark ……,

which test(s) is/are further described in Exhibit 1 attached hereto, (hereinafter referred to as “the

Product(s)”, and information relating thereto (hereinafter referred as the “the Information”). WHO is

interested in having the Product(s) evaluated and tested in the WHO/TDR-FIND Malaria Rapid

Diagnostic Test (RDT) Product Testing Programme, jointly coordinated by the WHO, the

UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases

(WHO/TDR), and the Foundation for Innovative New Diagnostics (FIND) hereinafter referred to as

"WHO/TDR-FIND Malaria Rapid Diagnostic Test (RDT) Product Testing Programme".

Therefore, the Parties have agreed as follows:

(1) The Company shall disclose and furnish to WHO the Information and sufficient quantities of the

Product(s) in order to enable WHO to assess the Information and arrange for such evaluations of

the Product(s), as WHO may determine, are reasonably necessary to assess the performance of

the Product(s) and its/their suitability for use at the primary health care settings in developing

countries. At the conclusion of the testing and evaluation process, WHO will report the results

thereof to the Company and, at the Company’s request and cost, return or destroy the

Information and any unused quantities of the Product(s). For the avoidance of doubt,

"Information" as used herein does not include the data and information resulting from the testing

and evaluation process (including the stability test(s) performed by the Company and submitted

to WHO as part of the Product Testing Programme), any other testing results and the reports

generated as a result of this Agreement (all the foregoing hereinafter jointly referred to as "the


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Testing Results"). Such Testing Results shall belong to WHO (subject always, however, to the

other provisions of this Agreement).

(2) If and to the extent that the Information has been marked by the Company as "Confidential",

WHO shall treat such Information as confidential and proprietary for a period of five years after

disclosure to it. In this connection, WHO shall take all reasonable measures to ensure that the

Information in question is not used for any purpose other than the aforementioned evaluation

and testing activities and is not disclosed or provided to any person who is not bound by similar

obligations of confidentiality and restrictions on use as contained in this Agreement.

(3) WHO shall not be bound by any obligation of confidentiality or restriction on use to the extent it is

clearly able to demonstrate that any part of the Information:

a) was known to WHO prior to any disclosure by the Company to WHO; or

b) was in the public domain at the time of disclosure by the Company to WHO; or

c) becomes part of the public domain through no fault of WHO; or

d) becomes available to WHO from a third party not in breach of any legal obligations of

confidentiality to the Company.

(4) The Company undertakes to abide by similar obligations of confidentiality and restrictions on use

as contained in paragraphs 2 and 3 above with regard to the Testing Results (regardless of

whether or not such Testing Results have been marked as "confidential").

(5) The provision of Product(s), Information, and Testing Results shall not in itself be construed as

conveying rights under any patents or other intellectual property which either Party may have or

may hereafter obtain.

(6) Subject to the protection of each Party’s confidential information and the provisions of this

paragraph 6, Testing Results may be published by either Party. In order to avoid prejudicing

confidential information of the other Party, the submitting Party will transmit to the other Party for

its review, the material intended to be published at least 60 (sixty) working days before a

proposed publication is submitted to any editor, publisher, referee or meeting organizer. In the

absence of an objection by the other Party within the 60-day period concerning prejudice to its

confidential information, and provided that all other conditions of this paragraph 6 have been

met, the publication may proceed.

In connection with the foregoing, it is understood and agreed that notwithstanding any other

provisions in this Agreement, WHO shall be entitled to evaluate and publish the Testing Results,

and to exclusively control this evaluation and the content of the aforesaid publication, provided

that in order to avoid prejudice to the Company’s confidential Information disclosed to WHO


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pursuant to paragraphs 1 and 2 above, WHO shall submit any proposed publication to the

Company for review in accordance with the provisions of paragraph 6. For the avoidance of any

doubt, the Company shall only be entitled to object to a proposed publication if and to the extent

it contains any confidential Information of the Company, and not on the grounds that the

Company is not satisfied with the Testing Results and/or does not agree with WHO's evaluation

thereof.

The Company shall not proceed to the publication (or any other public disclosure) of any of the

Testing Results until such Results have been published by WHO and until the proposed

publication has been submitted to WHO for review in accordance with the provisions of

paragraph 6.

All publications of the results of any evaluation and testing activities carried out under this

Agreement shall include the following statement:

“This investigation was carried out as part of the "WHO/TDR-FIND Malaria Rapid Diagnostic

Test (RDT) Product Testing Programme ".

Other than as provided herein before, neither Party shall, in any statement or material of an

advertising or promotional nature, refer to the relationship of the Parties under this Agreement or

to the relationship of the other Party to the Product(s). The Company shall not, at any time, use,

nor allow any other parties to use, the participation in the Product Testing Programme and/or

publication by WHO of the Testing Results for commercial or promotional purposes. Under no

circumstances shall the Company or any other party be authorized to refer to WHO, the

Company's participation in the Product Testing Programme, and/or the publication of the Testing

Results by WHO, in any statement or material of an advertising or promotional nature, press

release and/or similar public statement and/or other material aimed at promoting the Company,

any other party and/or the Product(s).

(7) The Company shall provide the Information and sufficient quantities of the Product(s) to WHO, or

WHO’s designee(s), free of charge. Upon receipt of a written request to that effect, the

Company shall furthermore pay any and all costs relating to the evaluation and testing process

hereunder to WHO, or WHO’s designee(s), in advance, in accordance with WHO’s instructions.

In the event that WHO, or its designee(s), do not receive the Information, and sufficient quantities

of the Product(s) by the required deadlines, WHO shall be under no obligation to arrange for the

performance of any evaluation or testing activities in relation to the Product(s). Any balance of

funds provided by the Company, and remaining unspent upon the conclusion of the testing and

evaluation process shall be returned to the Company, unless otherwise agreed by the Parties.

(8) The Company hereby furthermore confirms that it has taken good note of, agrees with, accepts

and to the extent applicable, shall abide by, the provisions contained in the document, entitled


16

"Information for Manufacturers on WHO/TDR-FIND Malaria Rapid Diagnostic Test (RDT)

Product Testing Programme."

(9) Any dispute relating to the interpretation or application of this Agreement shall, unless amicably

settled, be subject to conciliation. In the event of failure of the latter, the dispute shall be settled

by arbitration. The arbitration shall be conducted in accordance with the modalities to be agreed

upon by the Parties or, in the absence of agreement, with the rules of arbitration of the

International Chamber of Commerce. The Parties shall accept the arbitral award as final.

On behalf of WHO: On behalf of the Company:

Signature: Signature:

Name: Name: Title: Title: Date: Date:


17

APPENDIX C

PRODUCTS TO BE INCLUDED FOR EVALUATION

Note: Please list up (number to be specified later by WHO-FIND) products, from the list of Expression of Interest (EOI) already submitted to FIND

(Please note that details of products in this form should have previously been submitted to FIND, and that no new product submitted in this form can be accepted for this round of testing).

Manufacturer Name Product 1

(Catalogue No.)

Product 2

(Catalogue No.)

Product 3

(Catalogue No.)

Name: Signature: Designation / position: Date:

Submit this form by email and hard copy to:

Julie Vercruysse FIND Foundation for Innovative New Diagnostics 16 Avenue de Budé 1202 Geneva Switzerland Tel: +41 (22) 710 05 97 Fax: +41 (22) 710 05 99 E-mail: [email protected] and [email protected] Not later than: 15 Jan 2010


18

APPENDIX D

(1): Joint-submission and joint-listing of products

In cases where products with different names are produced on the same production line, a single product may be submitted for testing and identical products may be

jointly listed with the results. The manufacturer of the each separate product should submit a completed EOI. (Such co-submission will require a written application

from all the companies concerned and provision of evidence that the products are the same (in the form of a letter signed by the entity indicated as manufacturer

(assembler), and a letter signed by the entity or entities indicated as owner(s) of the other products listed as identical). (Please fill the Table on the next page).

In this context, 'manufacture' or 'assembly' indicates production of the test to a state in which it is contained in packaging designed to protect it from environmental

degradation (i.e. moisture-proof envelope), including conduct of the quality assurance process in place to ensure product quality. The name of the company which is

the operator of the site of manufacture or assembly will be indicated in the list of jointly listed products, together with the name of the company or companies owning

the identical products.

In the case of jointly listed products, if one product included in a list of jointly listed products is deemed by WHO-FIND to warrant de-listing due to poor performance

on lot testing, all jointly listed products will be de-listed and require re-application for product testing. Where products are submitted individually for testing, they will

be deemed to be independently manufactured and removal from the product list will involve only the product(s) named.4

4 In cases where a product is de-listed due to poor performance, WHO-FIND may require specific lot testing of other products believed to be the same as the de-listed product.


19

APPENDIX D (cont'd.) (2) Request for joint-submission and joint-listing of products as part of the WHO/TDR-FIND Malaria Diagnostics Product Testing Programme

The following products are manufactured under identical conditions at the same manufacturing site, and are considered re-labelled versions of the same product. It is requested that they be listed as such in the publication of the performance results of product testing by WHO-FIND. It is understood that in the event WHO-FIND requires a product to be re-tested due to concerns regarding performance, jointly listed products will be considered as identical and will all be removed from the relevant WHO website lists.

Details of product submitted for testing and manufacturer of submitted product.

Name of manufacturer of product submitted for testing

Product Name

Catalogue Number

Plasmodium species

targeted1

Target Antigen

(s)

Format2

Dipstick: D Cassette: Ca

Card: Cd

Contact person and designation

Address

Email URL Contact numbers

Details of product to be listed as identical (re-labelled)

Name of owner / user of re-labelled product name

Product Name

Catalogue Number

Contact person and designation

Address

Email URL Contact numbers

Owner of the Product Signature_______________________ Name _____________________________ Designation / position _________________________ Manufacturer of the Product Signature_______________________ Name _____________________________ Designation / position _________________________ NOTE:

A separate signed letter must be provided by the manufacturer submitting product for testing, and the manufacturer/owner of the re-labelled product. Manufacturer requesting for joint submission of a product should send the Expression of Interest (Appendix A) and Appendix D by 30 Nov 2009.

20, AVENUE APPIA – CH-1211 GENEVA 27 – SWITZERLAND – TEL CENTRAL +41 22 791 2111 – FAX CENTRAL +41 22 791 3111 – WWW.WHO.INT

Tel. direct: +41 22 791 2230 Fax direct: +41 22 791 4854 E-mail : [email protected] In reply please refer to: Your reference:

To all manufacturers

10 December 2009

Dear Manufacturer, This letter is to acknowledge acceptance of your Expression of Interest in the WHO/TDR-FIND Malaria RDT Product Testing Programme: Round 3

The letter contains important reminders and information regarding the following topics.

1. Future deadlines 2. Limits on number of products for submission 3. Special notes on ISO requirements 4. Availability of panels of cultured parasites for preliminary testing of products by

manufacturers: 'manufacturer's panel' 5. Summary of product testing procedure 6. Provisional timeline for product testing 7. Relationship of product testing to WHO RDT procurement of malaria RDTs

Please do not hesitate to contact me with any questions or concerns. Yours sincerely,

Jane Cunningham Technical Officer WHO/TDR

Page 2/7 10 Dec. 09

Round 3 of WHO/TDR-FIND Malaria RDT Product Testing Programme

1. Next deadline

By 15 January 2010: the following items are required to qualify for participation in Round 3 of Product Testing Programme: These items are required even if they have been previously submitted for Rounds 1 or 2 of Product Testing.

Documents to be submitted by E-mail followed by hard copy to: Julie Vercruysse FIND 16 Avenue de Budé 1202 Geneva Switzerland Tel: +41 (22) 710 05 97 Fax: +41 (22) 710 05 99 E-mail: [email protected]

With a copy to [email protected]

A. TWO original signed copies of the Confidentiality Agreement (APPENDIX B1) (By hard copy and E-mail). One original will be signed by the Director of WHO/TDR and returned to you by mail.

B. Current ISO 13485:2003 - see explicit conditions below (By hard copy and E-mail)

i. In cases where an audit has been undertaken by an ISO 13485:2003 auditor,

but the certification is not yet available, WHO will accept a signed letter from the auditor confirming that an audit has been undertaken and the certificate is in process. The certificate must be submitted later by the final submission of products the end of March 2010.

ii. Some companies have submitted an ISO 13485:2003 certificate applying to a

site of product manufacturing and packaging under the name of another company, without having a valid ISO 13485:2003 certificate naming the company applying for product testing. ISO13485:2003 includes important provision covering customer care and follow up of non-conformities with expected performance. A product maybe accepted into Product Testing Programme if:

A current ISO13485:2003 is submitted covering the site of manufacturing

and packaging of the product;

1 these documents (Appendix B, Annex 3) were sent with the original announcement of the Round 3: EOI and are reattached to this correspondence - File name: Microsoft Word - EOI-Annex 1_2_3 _rev 19 Oct 09-FINAL.pdf. Alternatively, they can be downloaded at: http://www.wpro.who.int/sites/rdt/who_rdt_evaluation/call_for_testing_round3.htm

mailto:[email protected]

http://www.wpro.who.int/sites/rdt/who_rdt_evaluation/call_for_testing_round3.htm

Page 3/7 10 Dec. 09

A signed letter from the holder/company of the ISO13485:2003 stating that all manufacturing and packaging of the named products takes place under the facility covered by the ISO certification.

The submitting company must obtain ISO 9001 by the end of November 2010 for the products to remain on the list of products tested under the WHO Product Testing Programme and in subsequent publication of results.

C. Provision of an acceptable heat stability protocol of internal quality assurance

(information on ANNEX 31). (By E-mail)

2. Limit on number of products to be submitted by each manufacturer Due to the high volume of response to the EOI, we confirm that the number of products from each company will be limited in Round 3. The anticipated limit will be at either 2 products or 3 products per company. However, a definitive decision will be announced via email in mid-January 2010 once all applications have been reviewed and the final number of qualifying companies/products is determined. Therefore, you are NOT required to submit the final list of products and pamphlets (Appendix C1) by 15th January as indicated in earlier correspondence.

3. Ordering panels of cultured parasites (P. falciparum) for preliminary testing of products by manufacturers (optional)

A panel of samples derived from cultured P. falciparum, diluted and preserved at -80°C, are available, free of charge. This panel will be a subset of the Phase One panel used for product testing, and is intended to allow manufacturers to assess product quality prior to submitting lots to the Product Testing programme. The panel is detailed in Table 1 and can be requested by completing and returning Annex 1, of this document. Accessing this panel is optional, but recommended. This 'manufacturer's panel' has been prepared at US CDC and consists of aliquots of 5 cultured P. falciparum parasite lines from geographically different endemic areas. Each of these samples is provided at two parasite dilutions: 200, and 2,000 parasites per µl. The panel has been tested against a number of commercially-available HRP2-detecting and pLDH-detecting RDTs. The results indicate that all 2000 parasite/microL concentrations are expected to be detected by good quality RDTs. The 200 parasite/microL samples can be detected by some HRP2-detecting and pLDH-detecting RDTs but these samples are close to the detection limit of currently-available tests. Should your products fail to detect samples at 2000 parasite/microL, it is therefore likely that these products will not perform well in terms of antigen detection against the complete product testing panel, and your company should seriously consider whether or not you submit these products for further evaluation. As stated previously all results of RDTs submitted to WHO for evaluation will be published. Table 1. Sample panel available to manufacturers for screening prior to product submission.

Page 4/7 10 Dec. 09

Sample type n Antigen type and concentrationa Origin b Testing conditions

MANUFACTURERS PANEL Pf HRP2 pLDH aldolase

P. falciparum (Pf) culture lines 5 Type Conc. Conc. Conc.

ID: Name of the Pf strains :

ID: US03FBeninI/Benin I A 10.18 4.23 0.71 Benin, West Africa

ID: US02FSantaLucia/Santa Lucia B 4.38 4.76 1 El Salvador, Cen. Amer.

ID: US04FNigeriaXII/Nigeria XII * B 5.93 4.69 0.63 Nigeria, West Africa

ID: US03FFC27A3/FC27-A3 B 19.5 7.9 1.21 Papua New Guinea

ID: US03FPH1/PH-1 C 5.9 2.54 0.96 Philippines

Dilutions prepared: 200 and 2000 or 5000 parasites/μl)

Note : samples characterized by microscopy, molecular species diagnosis, Pf HRP2 sequencing, and quantitative antigen ELISA. a Indication of the parasite antigen (Pf HRP2 types A / B / C and HRP2, pLDH and aldolase antigen content (ng/mL) at 200 parasites/ml].content). b Geographical origin of parasite strains

* Pf culture line used as the reference standard for RDT stability testing at the CDC and by the manufacturers participating in the WHO/TDR-FIND RDT Evaluation Programme .

n = number of samples, p/µL = parasites per microlitre of blood.

Upon request, each manufacturer will receive a labeled panel consisting of frozen samples of each of these culture lines, as 15 aliquots of 50 microL diluted to 200 parasites/microL, and 2000 parasites/microL (Total 15 x 2 x 5 = 450 aliquots). Panels are provided free of charge, but the manufacturer is responsible for organizing and paying the costs of a courier, and organizing permits and all passage through ports and customs once the sample has left the production site at the United States Centre for Disease Control and Prevention (US CDC) in Atlanta, USA. Note the samples should be shipped on dry ice (-78°C). The courier company needs to liaise with the Ms. Sophie Jones via email ([email protected]) for arranging the schedules of pick up of the panel. Loss or damage to the shipments is the responsibility of consignee, and the shipper engaged by the consignee. Due to the limited number of available samples, WHO can not guarantee that damaged or lost shipments will be replaced. Contact details for ordering panels: Order by email: Sophie Jones: [email protected] cc: [email protected]

Consigner address for courier

Sophie Jones Centres for Disease Control and Prevention Malaria Branch, Division for Parasitic Diseases Bldg 109, Room 1118.6, MS F-36 4770 Buford Hwy NE Chamblee, GA 30341 (USA) ph: 770-488-3771 ; fax 770-488-4454 Email: [email protected]

Note: All orders must be in the format detailed in Annex 1 (of this document).



Page 5/7 10 Dec. 09

4. Summary of product testing procedure (Figures 1a,b) Figures 1 and 2 give a brief outline of product testing. A detailed description of the Product Testing Programme and Standard operating procedures (Methods Manual for Product Testing of Malaria Rapid Diagnostic Tests (Version 2) can be found at the following website: http://www.wpro.who.int/sites/rdt/documents/list.htm Figure 1:

a) Outline of the Product Testing Protocol

Evidence of quality

manufacturing

RDTs to specimen bank with temperature monitor

Review of results by technical group and subsequently circulated to manufacturers

Performance versus panel

(Phase 1 and 2)

Heat Stability Ease-of-Use assessment

Longer-term stability test by manufacturer

Final publication

b) Phase 1 and Phase 2: Challenge Panel for malaria RDT Product Testing

Panel Panel samples RDTs tested at each dilution

Phase 1 Pf culture panel 20 lines 2 low, 1 high

Wild type Pf ≈100 2 low, 1 high

Wildtype Pv ≈35 2 low, 1 high

Phase 2

Negative panel 100 2

Note: The final panel may vary slightly according to the availability of samples acceptable for testing after characterization is completed. Note: Each lot must detect 80% of the high density culture samples in Phase 1 before progressing to Phase II evaluation panel.

http://www.wpro.who.int/sites/rdt/documents/list.htm

Page 6/7 10 Dec. 09

5. Provisional timetable for product testing (times may change)

6. Relationship of product testing to WHO RDT procurement, and to WHO prequalification of malaria RDTs

As with the 1st and 2nd round of Product testing, the results of the 3rd round of WHO/TDR-FIND Malaria RDT Product Testing Programme will form the basis of procurement recommendations of WHO and the WHO tendering programme. RDTs must be submitted to Rounds 1, 2 or 3 of Product Testing Programme to be eligible for future WHO procurement. Products accepted for the product testing programme will be listed on the WHO web site. If products were submitted to Rounds 1 or 2 of Product Testing then this is sufficient for being eligible to be listed for WHO bulk procurement. Products submitted to previous rounds may be re-submitted to Round 3, but this is not necessary. If products are resubmitted, then from a WHO procurement perspective, the test results from Round 3, will replace results from Round 1 and/or Round 2.

Page 7/7 10 Dec. 09

Annex 1: Order Form - 'Manufacturers Panel' - culture-derived P. falciparum samples

Manufacturer Name

Manufacturer (consignee) address

Courier company contracted for transport (including full contact details).

Date requested for collection of samples from CDC (dd/mm/yy):

Note: It is entirely the manufacturer's responsibility to contract the shipping agent (courier) and undertake all necessary payments for transport, including supply of packaging materials and dry ice. The manufacturer should be experienced at transporting goods on dry ice (-78ºC). Note that the consignment contains dead malaria parasites in human blood:

Category B Biological Substance - UN 3373 Human Blood Samples (Frozen) containing dead malaria parasites Quantity: 150 vials containing 50 μL For Laboratory Testing Only Human material containing no animal material and not of tissue culture origin.

The shipping agent (courier) MUST contact CDC beforehand to arrange pick-up of samples. US CDC has the discretion to vary the preferred pick-up date. Contact details for ordering panels: Order by email: Sophie Jones: [email protected] cc: [email protected]




Page 7/7 10 Dec. 09

Annex 1: Order Form - 'Manufacturers Panel' - culture-derived P. falciparum samples

Manufacturer Name






The shipping agent (courier) MUST contact CDC beforehand to arrange pick-up of samples. US CDC has the discretion to vary the preferred pick-up date. Contact details for ordering panels: Order by email: Sophie Jones: [email protected] cc: [email protected]






All manufacturers

31 January, 2010

Re: Round 3 of WHO/TDR-FIND Malaria RDT Product Testing Dear Manufacturers, The documents submitted have been reviewed and we are pleased to confirm acceptance of your application to the WHO/TDR-FIND Malaria RDT Product Testing Programme - Round 3.

1. Limit on number of products to be submitted by each manufacturer In order to keep to the programme's budget and timelines, we must limit the final number of products per company to three. Therefore, if > 3 products were previously proposed for evaluation, one product must be dropped. All participants should now complete the form - Annex 1 (enclosed) containing the final list of products and submit this information along with corresponding package inserts via email by February 10, 2010. A hard copy must follow by mail as follows:

Julie Vercruysse FIND 16 Avenue de Budé 1202 Geneva Switzerland Tel: +41 (22) 710 05 97 Fax: +41 (22) 710 05 99 E-mail: [email protected] and [email protected]

Page 2

2. Ordering panels of cultured parasites (P. falciparum) for preliminary testing of products by manufacturers (OPTIONAL)

The manufacturer's panels will be available shortly (early March 2010) and as per earlier instructions, to request a panel, the company must complete and following instructions outlined in Annex 2 (enclosed).

3. Temperature monitors (OPTIONAL) One temperature monitor per company will be available (for loan) in early March 2010, at no cost, to use during the transportation of RDT lots to Centre for Disease Control and Prevention (CDC), USA. To request a temperature monitor, send an email to: [email protected] with a copy to [email protected] . Following the request you will receive a sample envelope for the temperature monitor with information required to be completed by the manufacturer.

4. Obtaining the parasite dilutions for manufacturing site thermal stability testing

All information is in the enclosed Annex 3 including a cover note, stability test protocol and results template.

5. Shipment of RDTs to CDC, Atlanta

Detailed instructions for shipment of RDTs along with confirmation of the final product list, will follow in a separate letter by mid-February. As in previous Rounds, products will be expected to arrive at the CDC, Atlanta by 30 March.

Please don't hesitate to contact me should you have any questions or concerns. Sincerely,

Dr. Jane Cunningham

Technical Officer WHO/IER/TDR/DQR World Health Organization

ANNEX 1

PRODUCTS TO BE INCLUDED FOR EVALUATION

Note: Please list maximum 3 products, from the list of Expression of Interest (EOI) already submitted to FIND

(Please note that details of products in this form should have previously been submitted to FIND, and that no new product submitted in this form can be accepted for this round of testing).

Manufacturer Name Product 1

(Catalogue No.)

Product 2

(Catalogue No.)

Product 3

(Catalogue No.)

PACKAGE INSERT

INCLUDED

Name: Signature: Designation / position: Date:

Submit this form AND PACKAGE INSERTS by email and hard copy to:

Julie Vercruysse FIND 16 Avenue de Budé 1202 Geneva Switzerland Tel: +41 (22) 710 05 97 Fax: +41 (22) 710 05 99 E-mail: [email protected] and [email protected] Not later than: 10 February 2010

ANNEX 2:

Order Form - 'Manufacturers Panel' - culture-derived P. falciparum samples

Manufacturer Name






The shipping agent (courier) MUST contact CDC beforehand to arrange pick-up of samples. US CDC has the discretion to vary the preferred pick-up date.

Contact details for ordering panels:

Order by email:

Sophie Jones: [email protected] cc: [email protected]



ANNEX 3

Information pack on manufacturing site Stability Testing

1. Covering note on Stability Testing requirement at manufacturing site This note outlines requirements for the manufacturing site stability test of malaria RDT products submitted for product testing. The testing process is detailed in the accompanying standard operating procedures (SOP 2.2.d), and a standard report form is provided in electronic format (by email) and hard copy. Please keep this note with SOP 2.2.d for future reference. This stability test was specified in previous correspondence as a requirement for participation in the product testing programme, which has now commenced. The test is intended to provide real-time data on thermal stability at the maximum specified temperature recommended for each product, for the duration of the recommended shelf-life, against standardized reference parasite-positive blood samples. The products of your company accepted into the programme are listed in a letter document accompanying this document. Production lots to be tested The manufacturing site stability test should be performed using the same production lots as those submitted for product testing to the US Centers for Disease Control and Prevention (CDC), Atlanta, USA. If this is not possible, two other lots of the same product should be used. Duration of Testing The initial test should be conducted by 30 May 2010, and both RDT lots should be under incubation by this date. If this is not possible, WHO/TDR-FIND should be informed immediately at the contact address below. Testing should continue every 3 months until the expiry date of each lot of RDTs. Recording and Reporting Results The line intensity should be rated using the colour intensity rating scale provided (these will be sent by courier later). The colour chart closest to the colour of the RDT test lines should be selected, and used throughout. Note that the intensity rating is not intended to compare visibility of lines between products, but to allow a reduction in intensity over time to be noted.

Results should be communicated to WHO/TDR-FIND every 3 months by email attachment to [email protected] in the format provided and to [email protected] Blood Reference Standard (Obtaining, and use of) The reference standard is a culture-derived parasite P. falciparum parasite sample (Nigeria XII) which forms part of the phase 1 testing panel of the product testing programme and is the standard used for the thermal stability component of the product testing underway at CDC in Atlanta, GA, USA.

CDC will provide sufficient aliquots of the parasite sample to test two lots of the products of each manufacturer, using the blood volume specified in the manufacturer's product instructions. Blood aliquots should be discarded after use, and not re-frozen. The samples are provided as 50 L aliquots in dilutions of 200 parasites/L and 2000 parasites/L. If the 200 parasites/uL dilution does not produce a positive test result on initial testing, this dilution may be excluded from the subsequent test at 3 monthly intervals, and the dilution of 2000 parasites/ alone used. The blood sample must be obtained from US CDC at the manufacturers expense. The samples must be transported frozen (on dry ice, -78C) and stored at least at -20C after receipt. Please note that the samples should be transported from CDC by engaging a courier experienced in the transport of blood samples on dry ice, and in the relevant customs clearance involved in such transport. The integrity of the samples during transport and on receipt, and the process of clearing through customs and obtaining relevant national regulatory approvals, is the responsibility of the manufacturer (consignee). WHO and CDC will assist with necessary documentation on request. The courier should be experienced at transporting goods on dry ice (-78ºC). Note that the consignment contains dead malaria parasites in human blood: Category B Biological Substance - UN 3373 Human Blood Samples (Frozen) containing dead malaria parasites Quantity: XXX* vials containing 50 μL For Laboratory Testing Only Human material containing no animal material and not of tissue culture origin. The shipping agent (courier) MUST contact CDC before hand to arrange pick-up of samples and relevant documentation. CDC has the discretion to vary the preferred pick-up date. Contact details for obtaining blood samples to be used in stability testing at the manufacturing site: Contact by email:

Sophie Jones: [email protected]

cc: [email protected]


Sophie Jones Centers for Disease Control and Prevention (CDC)

Malaria Branch, Division for Parasitic Diseases

Bldg 109, Room 1118.6, MS F-36

4770 Buford Hwy NE

Chamblee, GA 30341 ph: 770-488-3771 fax 770-488-4454

Email: [email protected]

The parasite-negative blood sample necessary as a control in the testing process should be provided by the manufacturer.

2. Stability Test Protocol

Stability Assessment at Manufacturing Site

PURPOSE This SOP describes the procedure for stability testing of a Rapid Diagnostic Test at the manufacturing site, using standards provided by the WHO/TDR-FIND Malaria Rapid Diagnostic Test Evaluation Programme. SCOPE This procedure applies to manufacturers participating in the malaria RDT product testing programme of WHO/TDR and FIND with the US Centers for Disease Control and Prevention.

TESTING PROCEDURE (Refer to Figure 1) 1. General

a) Testing should occur at Day = 0, using 24 RDTs from each of 2 lots (total 48), then 12 RDTs from each of 2 lots (total 24) at each 3 monthly interval for the duration of the manufacturer's recommended shelf life.

Test 8 RDTs against 200 parasites/μL


Test 8 RDTs against negative sample

b) Store sufficient RDTs in the incubator incubator /environmental chamber to allow testing of 40 RDTs (20 per lot) every 3 months for the remaining duration of the shelf-life designated for that product by the manufacturer, and sufficient RDTs at 4° C (2-8°C) to allow testing of RDTs (12 per lot) every 3 months for the remaining duration of the shelf-life.

c) Every three months, test 20 RDTs from each lot stored in the incubator and 12 from each lot stored at 4°C:

From 4°C storage:

Test 4 RDTs against 200 parasites/L



From incubator:




d) Incubated RDTs should be stored at the maximum storage temperature recommended by the manufacturer.

e) Allow a minimum 3 days to calibrate incubators prior to conducting baseline testing.

f) Incubator temperatures and refrigerator temperatures should be recorded daily on a chart attached to the incubator or closely accessible

g) Mark days when testing is due at 3 month intervals for remainder of shelf life.

h) RDTs should be stacked in incubators in their normal packaging (boxes / kits), allowing air circulation against at least 2 sides of box, and not in direct contact with walls or floor of incubator.

i) All documentation should be readily accessible if manufacturer site inspections occur.

Table A: Number of RDTs required per lot for STABILITY TESTING.

Test RDTs required per lot at storage temperature

RDT required per lot at 4o C

Total RDTs (both lots)

Baseline 24 48 Each 3 months 20 12 64 Expiry date 20 12 64 Example for 2 year shelf-life, 3 month old lot when testing commences: Baseline 24 48 6x3 months 120 72 384 Expiry date 20 12 64 Spare 20 12 64 Total per lot 184 96 560

2. Preparation of product and sample

a) Blood samples to be used as the positive standard for testing are supplied from WHO / CDC (manufacturer must arrange and fund courier), in aliquots of 200 parasites/microL and 2000 parasites/microL, and should be stored at ≤-20°C.

b) Test in air-conditioned (low humidity) environment, at ≤25°C with good lighting.

c) Thaw sufficient aliquots of blood samples designated for RDT stability testing for 30 minutes at room temperature (<30°C) (Each aliquot is approximately 50 microL, so for RDTs requiring 5 uL blood, it is recommended to thaw 3 samples)

d) Store samples aliquots at 4°C after thawing

e) All blood samples must be used within 8 hours of thaw. Do not re-freeze.

f) Withdraw the correct number of RDTs of each lot from storage (incubator and 4°C – Figure 1) and allow to reach room temperature before opening envelope.

g) Test the correct number of RDTs from each lot (diagram below), against aliquots of 200 parasites/microL and 2000 parasites/microL and parasite-negative samples. (If all RDTs have failed at 200 parasite/microL at a previous testing interval, this aliquot may be removed from the testing procedure at future testing intervals. Follow manufacturer's RDT preparation procedure for each product, using pipette or manufacturer's blood transfer device to obtain correct blood volume.

h) If both lots of a product fail to detect the 200 parasites/microL sample at the initial test, the 200 parasite/L sample may be excluded from future testing and subsequent tests at 3 month intervals conducted using the 2000 parasites/microL sample only.

3. Reading and reporting results

a) Read result within the time period specified by manufacturer, rating line intensity 0-4 against colour intensity chart provided (Use colour closest to colour of positive line). (Colour intensity charts sent to you by courier with other hard copies)

b) Record on the record sheet provided in hard copy and electronic copy.

c) Submit results to WHO/TDR-FIND at the specified intervals.

d) Submission of results may cease once all RDTs have failed at any testing interval.

Stability Evaluation at Manufacturing Site

Figure 1: Stability Test Flowchart

Select sufficient RDTs of each of 2 lots to test: 20 RDTs initially, 32 RDTs at 3 month intervals throughout shelf-life, and at end of shelf life. It is advised to add at least 64 additional RDTs to allow for errors in process.

Time = 0 Store at 4°C Sufficient for 12 RDTs per 3 months (each lot) (consider 12 spare)

Test every 3 months, each lot Test 4 RDTs against 200 parasites/L Test 4 RDTs against 2000 parasites/L Test 4 RDTs against negative sample

Record results (Form 36a)

Baseline testing 24 RDTs per lot

Test 8 RDTs against 200 parasites/μL Test 8 RDTs against 2000 parasites/μL Test 8 RDTs against negative sample

Store at maximum storage temperature specified in product instructions Sufficient for 20 RDTs per 3 months (each lot) (consider 20 spare) (Consider 40 spare)


Time = 3, 6, 9, 12, 15, 18 … mths to end of shelf life (or until all RDTs fail)

Time = Lot expiry date

Test each lot Test 4 RDTs against 200 parasites/L Test 4 RDTs against 2000 parasites/L Test 4 against negative sample

Test each lot Test 8 RDTs against 200 parasites/L Test 8 RDTs against 2000 parasites/L Test 4 RDTs against negative sample

Record results (Form 36a) Report results (cumulative)

Record results (Form

WHO/TDR-FIND Malaria RDT Product Testing Programme - Rd 3 - Letter 3 - Annexes

3. Stability Test Result template Form 036a: STABILITY TEST: MANUFACTURER’S RESULT SHEET

Technician (Name ……………………………………) Colour chart used:

Control Line 1 Line 2 Line 3 CommentInterpretation (species)

Negative

Negative

Negative

Negative

Negative

Negative

Negative

Negative

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

Product:Lot:

Parasite density:

Negative, 200, 2000 para/uL

Time of preparation

Time of reading

TIME OF READING (INTERVAL IN MONTHS) ('0', or '3', '6' etc):

Result: Rate colour intensity 0-4 using colour chart provided)

Manufacturer:

Result should be recorded according to intensity of line, referenced against 'colour rating chart' provided. 'Control': Control line. 'Line 1 -3': Test result lines, as appropriate for the product. Signed: …………………………………



22 February 2010

Dear Manufacturer,

Re: Round 3 of WHO/TDR-FIND Malaria RDT Product Testing

1. Confirmation of final list of products In follow up to recent email correspondence, we kindly request that you confirm via email (to [email protected]) the following products for inclusion in WHO/TDR-FIND Malaria RDT Product Testing Programme - Round 3 at US CDC:

ABC Catalog# 123 ABC Catalog# 123 ABC Catalog# 123

2. Obtaining panels of cultured parasites (P. falciparum) for preliminary

testing of products by manufacturers (OPTIONAL) As per the last correspondence (1 Feb, 2010), the manufacturer's panels are available. To request a panel, the company must complete and follow instructions outlined in Annex 1 (enclosed).

3. Temperature monitors (OPTIONAL) Temperature monitors will be shipped in specially formatted envelopes the week of 22 February 2010, to requesting parties.

Page 2

Instructions on how to fill in the required information on the envelopes is included in Annex 2 (enclosed). To request a temperature monitor, send an email to: [email protected] with a copy to [email protected] .

4. AMENDMENT TO PRODUCT TESTING REQUIREMENTS Manufacturing site thermal stability testing

The WHO Malaria Specimen Bank Committee has recommended that for Round 3, performance of on-site thermostability evaluation of the submitted lots by the manufacturer using a reference sample and SOP provided by the programme should be OPTIONAL. Submission of these results is no longer required. This was previously a requirement for participation in WHO/TDR-FIND Malaria Product Testing. However, should a manufacturer wish to continue to follow these procedures using the reference sample from US CDC, this will be made available. Further information is enclosed in Annex 3 including a cover note, stability test protocol and results template. 5. Shipment of RDTs to CDC, Atlanta Detailed instructions for shipment of RDTs are included in Annex 4. Products must arrive at the CDC, Atlanta by 30 March, 2010. Confirmation of receipt will be sent via email. 6. Protocol modifications for Round 3

In Round 3, heat stability testing at the CDC will NOT be performed on high density (2000 parasites/μl) P. falciparum culture samples. As noted above (4.), manufacturer site stability testing is no longer a requirement for participation in WHO/TDR-FIND Malaria RDT Product Testing.

Please don't hesitate to contact me should you have any questions or concerns. Sincerely,

Dr. Jane Cunningham Technical Officer WHO/IER/TDR/DQR World Health Organization

WHO/TDR-FIND Malaria RDT Product Testing - Round 3 - Letter 3b attachments

Annex 1(1): Availability of panels of cultured P. falciparum parasites for preliminary testing of products by manufacturers (optional)

A panel of samples derived from cultured P. falciparum, diluted and preserved at -80°C, are now available. This panel will be a subset of the Phase One panel used for product testing, and is intended to allow manufacturers to assess product quality prior to submitting lots to the Product Testing programme. The panel is detailed in Table 1. Accessing this panel is optional, but recommended. This 'manufacturer's panel' has been prepared at US CDC and consists of aliquots of 5 cultured P. falciparum parasite lines from geographically different endemic areas. Each of these samples is provided at different parasite dilutions: 200, and 2,000 parasites per µl. The panel has been tested against a number of commercially-available HRP2-detecting and pLDH-detecting RDTs. The results indicate that all 5000 parasite/microL concentrations are expected to be detected by good quality RDTs. The 200 parasite/microL samples can be detected by some HRP2-detecting pLDH and HRP2 RDTs but these samples are close to the limit of currently-available tests. Should your products fail to detect samples at 5000 parasite/microL, it is therefore likely that these products will not perform well in terms of antigen detection against the complete product testing panel, and your company should seriously consider whether or not you submit these products for further evaluation. As stated previously all results of RDTs submitted to WHO for evaluation will be published. Table 1. Sample panel available to manufacturers for screening prior to product submission.

Sample HRP2 sequence type1 Derivation of sample Benin I A Benin, Africa Santa Lucia B (high) El Salvador, Central America Nigeria XII B (medium) Nigeria, Africa FC27/A3 B (low) Papua New Guinea, Australasia PH1 C Philippines, Southeast Asia

Each manufacturer may receive a labelled panel consisting of frozen samples of each of these culture lines, as 15 aliquots of 50 microL diluted to 200 parasites/microL, and 5000 parasites/microL (Total 15 x 2 x 5 = 150 aliquots). Panels are provided free of charge, but the manufacturer is responsible for organizing and paying the costs of courier, and organizing all passage through ports and customs once the sample has left the production site at the United States Centre for Disease Control and Prevention (US CDC) in Atlanta, USA. Note the samples should be shipped on Dry Ice (-78°C). The courier company needs to liaise with the Sophie Jones of Centre for Disease Control and Prevention (CDC), Atlanta, USA ([email protected]) for arranging the schedules of pick up of the parasite dilution samples. Loss or spoilage of shipments is the responsibility of consignee, and the shipper engaged by the consignee. Due to the limited number of available samples, WHO can not guarantee that spoilt or lost shipments will be replaced.


Contact details for ordering panels: Order by email:



Sophie Jones Centres for Disease Control and Prevention Malaria Branch, Division for Parasitic Diseases Bldg 109, Room 1118.6, MS F-36 4770 Buford Hwy NE Chamblee, GA 30341 ph: 001 770-488-7458 fax 001 770-488-4454 Email: [email protected]

Note: All orders must be in the format detailed in Annex 1 (2) of this document.


Annex 1 (2): Order Form - 'Manufacturers Panel' - culture-derived P. falciparum samples

Manufacturer Name






The shipping agent (courier) MUST contact CDC beforehand to arrange pick-up of samples. US CDC has the discretion to vary the preferred pick-up date. Contact details for ordering panels:

Order by email:



Sophie Jones Centres for Disease Control and Prevention Malaria Branch, Division for Parasitic Diseases Bldg 109, Room 1118.6, MS F-36 4770 Buford Hwy NE Chamblee, GA 30341 ph: 001 770-488-7458 fax: 001 770-488-4454 Email: [email protected]


Annex 2: Temperature monitor envelope and information needed

Note:

1. The temperature monitors will be available to manufacturers cost-free upon request. (Optional)

2. The above picture is a sample envelope which the temperature monitor is sent to you, when you request it from [email protected]

3. Please fill in the information on the back of the envelope sent to you (which contains the

temperature monitor) and place it with your RDTs transported to Centre for Disease Control and Prevention (CDC), Atlanta, USA for Product testing.

4. The yellow highlighted sections show information that manufacturers need to fill in before sending

the temperature monitor with RDT products to CDC, USA. Please read the following instructions:

Please leave the monitor inside this envelope (there is no need to open the envelope).

ON THE BACK OF THE ENVELOPPE: Fill in the date & time when the envelope was placed in the box of RDT's;

ON THE BACK OF THE ENVELOPPE: Duly fill in the table in order to keep track of the temperature monitor’s location (Arrival + Departure). Please follow FIND’s example in blue.

Please place this envelope safely inside the box together with the RDT's before the lot is sent/shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta, USA.


Annex 3: Information pack on manufacturing site Stability Testing NOW OPTIONAL for ROUND 3 PARTICIPANTS

1. Covering note on Stability Testing requirement at manufacturing site This note outlines requirements for the manufacturing site stability test of malaria RDT products submitted for product testing. The testing process is detailed in the accompanying standard operating procedures (SOP 2.2.d), and a standard report form is provided in electronic format (by email) and hard copy. Please keep this note with SOP 2.2.d for future reference. This stability test was specified in previous correspondence as a requirement for participation in the product testing programme, which has now commenced. The test is intended to provide real-time data on thermal stability at the maximum specified temperature recommended for each product, for the duration of the recommended shelf-life, against standardized reference parasite-positive blood samples. The products of your company accepted into the programme are listed in a letter document accompanying this document. Production lots to be tested The manufacturing site stability test should be performed using the same production lots as those submitted for product testing to the US Centers for Disease Control and Prevention (CDC), Atlanta, USA. If this is not possible, two other lots of the same product should be used. Duration of Testing The initial test should be conducted by 30 May 2010, and both RDT lots should be under incubation by this date. If this is not possible, WHO/TDR-FIND should be informed immediately at the contact address below. Testing should continue every 3 months until the expiry date of each lot of RDTs. Recording and Reporting Results The line intensity should be rated using the colour intensity rating scale provided (these will be sent by courier later). The colour chart closest to the colour of the RDT test lines should be selected, and used throughout. Note that the intensity rating is not intended to compare visibility of lines between products, but to allow a reduction in intensity over time to be noted.

Results should be communicated to WHO/TDR-FIND every 3 months by email attachment to [email protected] in the format provided and to [email protected]


Blood Reference Standard (Obtaining, and use of) The reference standard is a culture-derived parasite P. falciparum parasite sample (Nigeria XII) which forms part of the phase 1 testing panel of the product testing programme and is the standard used for the thermal stability component of the product testing underway at CDC in Atlanta, GA, USA. CDC will provide sufficient aliquots of the parasite sample to test two lots of the products of each manufacturer, using the blood volume specified in the manufacturer's product instructions. Blood aliquots should be discarded after use, and not re-frozen. The samples are provided as 50 L aliquots in dilutions of 200 parasites/L and 2000 parasites/L. If the 200 parasites/uL dilution does not produce a positive test result on initial testing, this dilution may be excluded from the subsequent test at 3 monthly intervals, and the dilution of 2000 parasites/ alone used. The blood sample must be obtained from US CDC at the manufacturers expense. The samples must be transported frozen (on dry ice, -78C) and stored at least at -20C after receipt. Please note that the samples should be transported from CDC by engaging a courier experienced in the transport of blood samples on dry ice, and in the relevant customs clearance involved in such transport. The integrity of the samples during transport and on receipt, and the process of clearing through customs and obtaining relevant national regulatory approvals, is the responsibility of the manufacturer (consignee). WHO and CDC will assist with necessary documentation on request. The courier should be experienced at transporting goods on dry ice (-78ºC). Note that the consignment contains dead malaria parasites in human blood: Category B Biological Substance - UN 3373 Human Blood Samples (Frozen) containing dead malaria parasites Quantity: XXX* vials containing 50 μL For Laboratory Testing Only Human material containing no animal material and not of tissue culture origin. The shipping agent (courier) MUST contact CDC before hand to arrange pick-up of samples and relevant documentation. CDC has the discretion to vary the preferred pick-up date. Contact details for obtaining blood samples to be used in stability testing at the manufacturing site: Contact by email:

Sophie Jones: [email protected]

cc: [email protected]


Sophie Jones Centers for Disease Control and Prevention (CDC) Malaria Branch, Division for Parasitic Diseases Bldg 109, Room 1118.6, MS F-36 4770 Buford Hwy NE


Chamblee, GA 30341 ph: 770-488-3771 fax 770-488-4454 Email: [email protected]

The parasite-negative blood sample necessary as a control in the testing process should be provided by the manufacturer.


2. Stability Test Protocol

Stability Assessment at Manufacturing Site

PURPOSE This SOP describes the procedure for stability testing of a Rapid Diagnostic Test at the manufacturing site, using standards provided by the WHO/TDR-FIND Malaria Rapid Diagnostic Test Evaluation Programme. SCOPE This procedure applies to manufacturers participating in the malaria RDT product testing programme of WHO/TDR and FIND with the US Centers for Disease Control and Prevention.

TESTING PROCEDURE (Refer to Figure 1) 1. General

a) Testing should occur at Day = 0, using 24 RDTs from each of 2 lots (total 48), then 12 RDTs from each of 2 lots (total 24) at each 3 monthly interval for the duration of the manufacturer's recommended shelf life.




b) Store sufficient RDTs in the incubator incubator /environmental chamber to allow testing of 40 RDTs (20 per lot) every 3 months for the remaining duration of the shelf-life designated for that product by the manufacturer, and sufficient RDTs at 4° C (2-8°C) to allow testing of RDTs (12 per lot) every 3 months for the remaining duration of the shelf-life.

c) Every three months, test 20 RDTs from each lot stored in the incubator and 12 from each lot stored at 4°C:

From 4°C storage:




From incubator:




d) Incubated RDTs should be stored at the maximum storage temperature recommended by the manufacturer.

e) Allow a minimum 3 days to calibrate incubators prior to conducting baseline testing.


f) Incubator temperatures and refrigerator temperatures should be recorded daily on a chart attached to the incubator or closely accessible

g) Mark days when testing is due at 3 month intervals for remainder of shelf life.

h) RDTs should be stacked in incubators in their normal packaging (boxes / kits), allowing air circulation against at least 2 sides of box, and not in direct contact with walls or floor of incubator.

i) All documentation should be readily accessible if manufacturer site inspections occur.

Table A: Number of RDTs required per lot for STABILITY TESTING.

Test RDTs required per lot at storage temperature

RDT required per lot at 4o C

Total RDTs (both lots)

Baseline 24 48 Each 3 months 20 12 64 Expiry date 20 12 64 Example for 2 year shelf-life, 3 month old lot when testing commences: Baseline 24 48 6x3 months 120 72 384 Expiry date 20 12 64 Spare 20 12 64 Total per lot 184 96 560

2. Preparation of product and sample

a) Blood samples to be used as the positive standard for testing are supplied from WHO / CDC (manufacturer must arrange and fund courier), in aliquots of 200 parasites/microL and 2000 parasites/microL, and should be stored at ≤-20°C.

b) Test in air-conditioned (low humidity) environment, at ≤25°C with good lighting.

c) Thaw sufficient aliquots of blood samples designated for RDT stability testing for 30 minutes at room temperature (<30°C) (Each aliquot is approximately 50 microL, so for RDTs requiring 5 uL blood, it is recommended to thaw 3 samples)

d) Store samples aliquots at 4°C after thawing

e) All blood samples must be used within 8 hours of thaw. Do not re-freeze.

f) Withdraw the correct number of RDTs of each lot from storage (incubator and 4°C – Figure 1) and allow to reach room temperature before opening envelope.

g) Test the correct number of RDTs from each lot (diagram below), against aliquots of 200 parasites/microL and 2000 parasites/microL and parasite-negative samples. (If all RDTs have failed at 200 parasite/microL at a previous testing interval, this aliquot may be removed from the testing procedure at future testing intervals. Follow manufacturer's RDT preparation procedure for each product, using pipette or manufacturer's blood transfer device to obtain correct blood volume.

h) If both lots of a product fail to detect the 200 parasites/microL sample at the initial test, the 200 parasite/L sample may be excluded from future testing and subsequent tests at 3 month intervals conducted using the 2000 parasites/microL sample only.


3. Reading and reporting results

a) Read result within the time period specified by manufacturer, rating line intensity 0-4 against colour intensity chart provided (Use colour closest to colour of positive line). (Colour intensity charts sent to you by courier with other hard copies)

b) Record on the record sheet provided in hard copy and electronic copy.

c) Submit results to WHO/TDR-FIND at the specified intervals.

d) Submission of results may cease once all RDTs have failed at any testing interval.


Stability Evaluation at Manufacturing Site

Figure 1: Stability Test Flowchart

Select sufficient RDTs of each of 2 lots to test: 20 RDTs initially, 32 RDTs at 3 month intervals throughout shelf-life, and at end of shelf life. It is advised to add at least 64 additional RDTs to allow for errors in process.

Time = 0 Store at 4°C Sufficient for 12 RDTs per 3 months (each lot) (consider 12 spare)


Record results (Form 36a)

Baseline testing 24 RDTs per lot

Test 8 RDTs against 200 parasites/μL Test 8 RDTs against 2000 parasites/μL Test 8 RDTs against negative sample

Store at maximum storage temperature specified in product instructions Sufficient for 20 RDTs per 3 months (each lot) (consider 20 spare) (Consider 40 spare)


Time = 3, 6, 9, 12, 15, 18 … mths to end of shelf life (or until all RDTs fail)

Time = Lot expiry date

Test each lot Test 4 RDTs against 200 parasites/L Test 4 RDTs against 2000 parasites/L Test 4 against negative sample

Test each lot Test 8 RDTs against 200 parasites/L Test 8 RDTs against 2000 parasites/L Test 4 RDTs against negative sample

Record results (Form 36a) Report results (cumulative)

Record results (Form


3. Stability Test Result template Form 036a: STABILITY TEST: MANUFACTURER’S RESULT SHEET

Technician (Name ……………………………………) Colour chart used:

Control Line 1 Line 2 Line 3 Comment Interpretation (species)

Negative

Negative

Negative

Negative

Negative

Negative

Negative

Negative

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

200 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

2000 para/L

Product:Lot:

Parasite density:

Negative, 200, 2000 para/uL

Time of preparation

Time of reading

TIME OF READING (INTERVAL IN MONTHS) ('0', or '3', '6' etc):

Result: Rate colour intensity 0-4 using colour chart provided)

Manufacturer:

Result should be recorded according to intensity of line, referenced against 'colour rating chart' provided. 'Control': Control line. 'Line 1 -3': Test result lines, as appropriate for the product. Signed: …………………………………


Annex 4: SOPs for transportation of products to US CDC

1. Products can be accompanied by a temperature monitor provided by WHO cost free upon request to [email protected] with a copy to [email protected].

2. The temperature monitor cover envelope must be duly filled in by the manufacturer

according to the instructions in Annex 2 of this letter. 3. Temperature monitor should be placed with the cover envelope inside with the RDT

products during transportation. 4. Appropriate number of products, 1100 products from each of two lots for each

product listed on the final products list must be submitted to Centre for Disease Control and Prevention (CDC), Atlanta, USA by 30th March 2010.

Shipping address:

Sophie Jones & John Barnwell Center for Disease Control and Prevention Chief, Laboratory Research and Development Unit Malaria Branch, Division of Parasitic Diseases Bldg. 109, Room 1121 MS F-36 4770 Buford Highway NE, 30341, Georgia, USA Email: [email protected] [email protected] Phone: 770-488-7458

5. It is advisable to use the phrase '' These Malaria RDT kits are for in vitro diagnostic use in

humans and not for use in animals. These kits are for evaluation purposes by US CDC under the WHO/TDR-FIND Malaria RDT Product Testing Programme Round 3. These will not be used for any in vitro diagnostic purposes within the territory of United States of America'' on the RDT courier boxes being transported to US CDC to minimize the custom issues.

6. In cases of unexpected custom issues or other delays, WHO([email protected]) and

FIND ([email protected]) should be informed of proof of products leaving manufacturing site before the deadline, other related correspondence, courier tracking numbers etc and these special situations need to be discussed with WHO Malaria Specimen Bank Steering Committee for eligibility for participation in the Programme and conveyed to manufacturers accordingly.

Manufacturer Product Name Catalogue No

ABON Biopharm (Hangzhou) Co. Ltd ABON Malaria Pan/P.f. Rapid Test Device (Whole Blood) IMA-B402 HRP2 pan aldolase

CareStart ™Malaria pLDH 3 Line Test G0121 pan pLDH pf pLDH

CareStart™ Malaria/Pregnancy Combo (pLDH/HRP2/HCG) G0221 HRP2 pan pLDH HCG

CareStart™ Malaria Screen G0231 Pf HRP2/Pf pLDH pan pLDH

ACON Biotech (Hangzhou) Co. Ltd Surestep™ Malaria Pf/Pan Rapid Test Device (Whole Blood) IMA-T402 HRP2 pan aldolase

Malaria pf (pLDH) / PAN-pLDH Test Device MFV-124 pan pLDH pf pLDH

Malaria pf (HRP II) / pv (pLDH) Antigen Detection Test Device MFV-124V pv pLDH HRP2

Malaria pf (HRP II) / (PAN-LDH) Antigen Detection Test Device MFV-124R pan pLDH HRP2

Nano Sign Malaria Pf Ag RMAF10 HRP2

NanoSign Malaria Pf/Pan Ag RMAP10 HRP2 pan pLDH

NanoSign Malaria Pf/Pv Ag RMAD10 pan pLDH pf pLDH

BIONOTE MALARIA P.f&P.v Ag Rapid Test Kit RG19-12 HRP2 pv pLDH

BIONOTE MALARIA P.f&Pan Ag Rapid Test Kit RG19-08 HRP2 pan pLDH

BIONOTE MALARIA P.f Ag Rapid Test Kit RG19-11 HRP2

IMMUNOQUICK CONTACT falciparum 0519K25 HRP2

IMMUNOQUICK CONTACT MALARIA +4 0525K25 HRP2 pan pLDH

Blue Cross Bio-Medical (Beijing) Co., Ltd. One Step Malaria P.F Test (cassette) 522352 HRP2

Core™ Malaria Pf MAL-190020 HRP2

Core™ Malaria Pv/Pf Mal-190022 HRP2 pv pLDH

Core™ Malaria Pan/Pv/Pf Mal-190026 HRP2 pan pLDH Pv pLDH

OnSite Pf Ag Rapid Test R0114C HRP2

OnSite Pf/Pan Malaria Ag Rapid Test R0113C HRP2 pan pLDH

OnSite Malaria Pf/Pv Ag Rapid Test R0112C HRP2 Pv pLDH

DiaMed - A Division of Bio-Rad OptiMAL-IT 710024 Pan pLDH Pf pLDH

Dima • Gesellschaft für Diagnostika mbH Malaria Pan test MAL-W23N-001 HRP2 pan aldolase

Access Bio, Inc.

Bioland, Ltd

BioNote,Inc.

Biosynex

Manufacturers and products accepted into Round 3 of WHO Malaria RDT Product Testing Programme

Target antigen(s)

CTK Biotech, Inc.

AZOG,Inc

Core Diagnostics

ICT Diagnostics Malaria Combo ML02 HRP2 pan aldolase

ICT Diagnostics Malaria Dual ML03 HRP2 pan pLDH

ICT Diagnostics Malaria P.f ML01 HRP2

Advanced Quality™ One Step Malaria P.f/P.v Tri-line Test ITP11003 TC40 HRP2 pv pLDH

Advanced Quality™ One Step Malaria P.f Test ITP11002 TC40 HRP2

J. Mitra & Co. Pvt. Ltd. Advantage Malaria Card IR211025 HRP2 Pv pLDH

Paracheck® Pf Device - Rapid test for P. falciparum Malaria 30301025 HRP2

Paracheck® Pf Dipstick - Rapid test for P. falciparum Malaria 30302025 HRP2

Orgenics Ltd. (Inverness Medical Innovations) Clearview® Malaria pLDH 70884025 pan pLDH

SD BIOLINE Malaria Ag 05FK40 pan pLDH pf pLDH

SD BIOLINE Malaria Ag P.f/Pan 05FK60 HRP2 pan pLDH

SD BIOLINE Malaria Ag P.f (HRP2/pLDH) 05FK90 HRP2 Pf pLDH

ParaHIT® - f (Device) 55IC102-10 HRP2

ParaHIT® - f (Dipstick) 55IC101-10 HRP2

diagnosticks MALARIA (Pan) Cassette MPNWBC1007.3 pan pLDH

diagnosticks MALARIA (Pan/Pf) Cassette MPNFWBC1007.4 HRP2 pan pLDH

diagnosticks MALARIA (Pan/Pv/Pf) Cassette MPNVFC1007.5 HRP2 pan pLDH Pv pLDH

Clearview Malaria Combo VB11 HRP2 Aldolase

Clearview Malaria Pf VB01 HRP2

Clearview Malaria Dual Test Device VB20 HRP2 pan pLDH

One Step Malaria P.f./Pan Whole Blood Test W56-C HRP2 pan pLDH

One Step Malaria P.f Test W37-C HRP2

Malascan™ Device - Rapid test for Malaria Pf/Pan 50402025 HRP2 pan aldolase

Parabank™ Device - Rapid test for Malaria Pan 50301025 pan pLDH

Parascreen™ Device -Rapid test for Malaria Pan/Pf 50310025 HRP2 pan pLDH

Span Diagnotics Ltd.

SSA Diagnostics & Biotech Systems

Vision Biotech (Pty) Ltd

R & R Marketing / ICT Diagnostics

InTec Products, Inc.

Orchid Biomedical Systems

Standard Diagnostics Inc.

Zephyr Biomedical Systems

Guangzhou Wondfo Biotech Co. Ltd.

WHO Global Malaria Programme Information note on recommended selection criteria for procurement of malaria rapid diagnostic tests (RDTs)

- 20 December 2012 -

In view of the increasing demand of countries to scale-up malaria diagnostics following the large-scale introduction of expensive antimalarial medicines, and the decreasing malaria trends in many countries, there is a need for guidance in the selection of malaria rapid diagnostics that meet international quality standards. This WHO note aims to provide information on both the criteria which have been recommended for and additional considerations which play a role in the procurement of malaria rapid diagnostic tests.

WHO policy on malaria diagnosis

WHO recommends parasitological confirmation of malaria through quality assured diagnosis in all settings before treatment is started1. Treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible, i.e. not available within two hours of patients presenting for treatment. Prompt diagnostic confirmation of malaria can be achieved through quality microscopy or quality rapid diagnostic tests detecting Plasmodium falciparum and/or Plasmodium vivax infections. In most countries both diagnostic methods are needed, as microscopy and RDTs often play different roles according to the clinical situations or the setting. WHO Malaria RDT Product Testing Programme

The heterogeneous diagnostic performance of more than 200 malaria RDTs currently available in the market can undermine the confidence of health professionals in the accuracy of these tests. The WHO Malaria RDT Product Testing Programme, coordinated by WHO/TDR and the Foundation for Innovative New Diagnostics (FIND) and executed in collaboration with US Centers for Disease Control and Prevention (CDC), provides comparative data on the performance of various RDTs available in the market to assist in procurement. Since 2008, 168 products have been evaluated over four rounds of WHO Malaria RDT Product Testing. This encompasses 128 unique products and 29 product resubmissions (see Annex 1). Each round of product testing begins with an invitation to all companies manufacturing under "ISO-13485: Medical devices - Quality management systems - Requirements for regulatory process" to submit up to 2-3 different RDTs for evaluation. The RDTs are evaluated against panels of cultured P. falciparum parasites (n=20), panels of patient-derived P. falciparum (n~100) and P. vivax (n~35) parasites, and a parasite-negative panel (n=100). The panel detection score (PDS)2, key parameter of the assessment, is thus not a measure of RDT clinical sensitivity or positivity rate against the panel but rather a combined measure of positivity rate along with inter-test and inter-lot consistency. In addition, thermal stability of the products is assessed after 2 months of storage at elevated temperatures (35°C, 45°C) and 75% humidity, and ease of use is also evaluated. The full report of results of all Rounds 1, 2, 3 and 4 is available at: http://www.who.int/iris/bitstream/10665/77748/1/9789241504720_eng.pdf.

1 The WHO Guidelines for the treatment of malaria, 2nd edition 2010, are available at: http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf 2 The term ‘panel detection score’ (PDS) is a composite index of test positivity as well as of inter-test and inter-lot consistency in performance. Panel detection score is not equivalent to sensitivity - see page 18 of the report of the Round 2 WHO malaria RDT product testing for a detailed description of this parameter (http://whqlibdoc.who.int/publications/2010/9789241599467_eng.pdf ).

2

WHO selection criteria for the procurement of RDTs

Experts convened at the Inaugural Meeting of the Malaria Policy Advisory Committee (MPAC), held in Geneva in early 2012, updated the WHO recommendations for the procurement of RDTs. Products should be selected in line with the following set of criteria, based on the results of the assessment of the WHO Malaria RDT Product Testing Programme3:

(A) For the detection of Plasmodium falciparum (Pf) in all transmission settings the panel detection score (PDS) against Pf samples should be at least 75% at 200 parasites/µL.

(B) For the detection of Plasmodium vivax (Pv) in all transmission settings the panel detection score (PDS) against Pv samples should be at least 75% at 200 parasites/µL.

(C) The false positive rate should be less than 10%.

(D) The invalid rate4 should be less than 5%.

FIND’s web-based interactive guide for the selection of malaria RDTs

Based on the results of Rounds 1-4 of the WHO Malaria RDT Product Testing Programme, FIND has developed a web-based interactive guide which allows to select suitable malaria RDTs on the basis of the following parameters: i) target malaria species, ii) minimum panel detection score for P. falciparum at 200 and 2000 parasites/µL, iii) minimum panel detection score for P. vivax at 200 and 2000 parasites/µL, iv) maximum false positive rate, v) maximum invalid rate, vi) test format and vii) heat stability. This guide is available at:

http://www.finddiagnostics.org/programs/malaria/find_activities/product_testing/malaria-rdt-product-testing.

Additional considerations relevant for procurement of malaria RDTs

Stability requirements at temperatures of intended storage, transport and use

RDTs submitted to WHO for malaria RDT product testing are evaluated for positivity against a single cultured P. falciparum isolate at 200 parasites/µL at baseline and after 60 days of incubation at 35°C and 45°C. In this regard, it is recommended to select RDTs with high thermal stability for areas with very high temperatures.

Ease of use and training requirements for the health workers

RDTs submitted to WHO for malaria RDT product testing are also evaluated for blood safety, instruction quality, number of steps, time to results, blood transfer device, format and kit completeness. Cassettes and cards are easier to use than dipsticks. For reasons of blood safety, kits that include lancets and alcohol swabs are preferred over kits which do not contain these items. Dipsticks are more suitable for settings with a laboratory facility.

3 The full report of the Round 4 of WHO Malaria RDT Product Testing Programme is available at: http://www.who.int/iris/bitstream/10665/77748/1/9789241504720_eng.pdf. 4 Proportion of tests deemed invalid, i.e. without visible control band.

3

Price

After having considered all of the above factors, good procurement practice requires that the price be taken into account. Programmatic needs5

The aim of this note is not to recommend to national health authorities to immediately replace with new tests the malaria RDTs which are already being deployed on a large scale. The diagnostic performance of RDTs in the field is dependent on all the parameters listed above, as well as on the effectiveness of training and supervision and on the functioning of the supply management system. Particularly for programmes that are already implementing RDTs on a large-scale, the continued deployment of the currently used tests may be appropriate until a decrease in malaria transmission triggers the need for RDTs with better performance in detecting low-level parasitaemia. Plans to replace RDTs should be developed carefully, taking into consideration the training and supervision requirements to support the introduction of the new RDTs, as well as the production capacity and expected lead time for deliveries from the suppliers of the new RDTs.

For a comprehensive guide to procurement of malaria RDTs extending beyond selection criteria see the WHO manual on Good practices for selecting and procuring rapid diagnostic tests for malaria6. This manual also includes practical advice on quantification, budgeting, tender technical specifications, management of tenders and contracts, supply management up to the receipt of goods at port of entry, monitoring of supplier performance and managing product variations. WHO-FIND Lot Testing Programme

As the performance of individual products is likely to vary between lots over time, WHO recommends that all RDT production lots be checked, either pre- or post-shipment, through a lot-testing centre collaborating with the WHO-FIND Malaria RDT Product Testing Programme, as part of good procurement practice. Currently, this service is free of charge through WHO-FIND’s two affiliated laboratories7. Full information on WHO recommended procedures for RDT lot testing are available at: http://www.wpro.who.int/sites/rdt/who_rdt_evaluation/lot_testing.htm.

5 This section is based on advice by WHO/GMP secretariat and not on recommendations of experts convened by a WHO Technical Consultation. 6 The WHO manual on Good practices for selecting and procuring rapid diagnostic tests for malaria, Geneva, World Health Organization, 2011, is available at: http://whqlibdoc.who.int/publications/2011/9789241501125_eng.pdf. 7 The Research Institute for Tropical Medicine (RITM), Muntinlupa City, The Philippines, and the Institut Pasteur of Cambodia (IPC), Phnom Penh, Cambodia.

4

Annex 1: Performance of Malaria RDTs in Rounds 1-4 of WHO Malaria RDT Product Testing

The table of results reproduced below is extrapolated from the Table S1, published in the Results of WHO Malaria RDT Product Testing: Summary Rounds 1-4 (available at http://www.who.int/iris/bitstream/10665/77748/1/9789241504720_eng.pdf), listing the tested products in alphabetical order by brand name, catalogue number and manufacturer. To this list, the above WHO-recommended criteria for RDT procurement have been applied. Using the results of WHO Malaria RDT Product Testing Programme Rounds 1-4 as the basis, a green box indicates that the corresponding recommended criterion has been met, whereas a white box indicates that this criterion has not been met.

Disclaimer: The list below does not in any way imply an endorsement, certification, warranty of fitness or recommendation by WHO of any company or product for any purpose, and does not imply preference over products of a similar nature that are not mentioned. WHO furthermore does not warrant that: (1) the list is complete and/or error free; and/or that (2) the products listed are of acceptable quality, have obtained regulatory approval in any country, or that their use is otherwise in accordance with the national laws and regulations of any country, including but not limited to patent laws. Inclusion in the list does not furthermore imply any approval by WHO of the products in question (which is the sole prerogative of national authorities). The list is not an exhaustive list of malaria RDTs. The list reflects those products which have been submitted for evaluation in Rounds 1-4 of the WHO Malaria RDT Product Testing Programme (full report available at: http://www.who.int/iris/bitstream/10665/77748/1/9789241504720_eng.pdf). Using the results of Rounds 1-4 as the basis, the criteria recommended for RDT procurement by WHO have been applied to this list. The fact that certain products are not included in the list means that they have not or not yet been submitted for evaluation in the WHO Malaria RDT Product Testing Programme and does not indicate anything in respect of such products' performance. WHO will not accept any liability or responsibility whatsoever for any injury, death, loss, damage, or other prejudice of any kind that may arise as a result of or in connection with the procurement, distribution and use of any product whatsoever included in the list. This list may not be used by manufacturers and suppliers for commercial or promotional purposes.

5

Performance of malaria RDTs in Rounds 1-4 of WHO Malaria RDT Product Testing Programme Performance criteria: A: P. falciparum panel detection score > 75% at 200 parasites/µl B: P. vivax panel detection score > 75% at 200 parasites/µl

C: False positive rate < 10% D: Invalid rate < 5%

Product Catalogue number*

Manufacturer Re-tested product

RDT format Performance criteria

A B C D

Pf only

ABON™ Malaria P.f. Rapid Test Device (Whole Blood)

IMA-402 ABON Biopharm (Hangzhou) Co.

Ltd Cassette

N/A

Advanced Quality™ One Step Malaria P.f Test

ITP11002TC40 InTec Products, Inc. √ Cassette

N/A

Advanced Quality™Malaria (p.f) POCT

ITP11002TC1 InTec Products, Inc.

Cassette

N/A

Advantage P.f. Malaria Card IR016025 J. Mitra & Co. Pvt. Ltd.

Card

N/A

BIOCREDIT Malaria pf(HRP II) HR0100 RapiGen Inc.

Cassette

N/A

BIONOTE MALARIA P.f. Ag Rapid Test Kit

RG19-11 Bionote,Inc.

Cassette

N/A

CareStart™ Malaria HRP2 (Pf) G0141 Access Bio, Inc.

Cassette

N/A

CareStart™ Malaria HRP2/pLDH Pf test

G0181 Access Bio, Inc.

Cassette

N/A

Clearview® Malaria P.f. VB01 Vision Biotech (Pty) Ltd √ Cassette

N/A

Core™ Malaria Pf MAL-190020 Core Diagnostics

Cassette

N/A

diagnosticks- Malaria (Pf) Cassette KMFC6001 SSA Diagnostics & Biotech Systems

Cassette

N/A

diagnosticks- Malaria (Pf) Dipstick KMFD6007 SSA Diagnostics & Biotech Systems

Dipstick

N/A

6




A B C D

First Response® Malaria Ag HRP2 I13FRC30 Premier Medical Corporation Ltd. Cassette N/A

FirstSign™ Malaria Pf 2100CB-25 Unimed International Inc. N/A

FirstSign™ – Malaria Pf Card Test -- Unimed International, Inc.

Cassette

N/A

Hexagon Malaria 58051 Human GmbH

Cassette

N/A

HiSens Malaria Ag Pf HRP2 Card HR3023 HBI Co., Ltd.

Card

N/A

ICT Diagnostics Malaria P.f. ML01 ICT Diagnostics √ Cassette

N/A

IMMUNOQUICK CONTACT falciparum 0519K25 Biosynex

Cassette

N/A

Immunoquick Malaria Falciparum 0502_K25 Biosynex

Dipstick

N/A

IND ONE STEP MALARIA ANTIGEN P.f 535-11 IND Diagnostics Inc.

Cassette

N/A

Malaria Plasmodium falciparum Rapid test Device (Whole blood)

IMA-402 ACON Laboratories, Inc.

Cassette

N/A

Maleriscan ® Malaria P.f Antigen Test MAT-PF-50 Bhat Bio-Tech India (Pte.) Ltd.

Cassette

N/A

NanoSign Malaria Pf Ag RMAF10 Bioland, Ltd

Cassette

N/A

One Step Malaria P.F Test (cassette) 522352 Blue Cross Bio-Medical (Beijing)

Co., Ltd. √ Cassette

N/A

One Step Malaria P.f Test W37-C Guangzhou Wondfo Biotech Co.

Ltd. √ Cassette

N/A

OnSight™ - Malaria Pf Test 511-25-DB Amgenix International, Inc.

Cassette

N/A

OnSite Pf Ag Rapid Test R0114C CTK Biotech, Inc. √ Cassette

N/A

7




A B C D

Paracheck® Pf Device- Rapid test for P. falciparum Malaria Ver. 3

30301025 Orchid Biomedical Systems √ Cassette

N/A

Paracheck® Pf Dipstick- Rapid test for P. falciparum Malaria Ver. 3

30302025 Orchid Biomedical Systems √ Dipstick

N/A

ParaHIT® - f (Device) 55IC102-50 Span Diagnostics Ltd. √ Cassette

N/A

ParaHIT® -f (Dipstick) 55IC101-50 Span Diagnostics Ltd. √ Dipstick

N/A

SD BIOLINE Malaria Ag P.f. (HRP2/pLDH)k

05FK90 Standard Diagnostics Inc.

Cassette

N/A

SD BIOLINE Malaria Ag Pf 05FK50 Standard Diagnostics, Inc.

Cassette

N/A

TrustyTM Malaria Antigen P.f. test A03-11-322 Artron Laboratories Inc.

Cassette

N/A

Pf and Pan

ABON Malaria Pan/P.f. Rapid Test Device

IMA-B402 ABON Biopharm (Hangzhou) Co.

Ltd. Cassette

ABON™ Plus Malaria P.f/Pan Rapid Test Device (Whole Blood)

IMA-T402 ABON Biopharm (Hangzhou) Co.

Ltd Cassette

Advantage Mal Card IR221025 J. Mitra & Co. Pvt. Ltd.

Card

AZOG Malaria pf (HRPII)/pf (LDH)/ (PAN-LDH) Antigen Detection Devicef

MFV-124F AZOG, INC.

Cassette

Binax Now Malaria Test IN660050 Inverness Medical Innovations,

Inc. Card

BIONOTE MALARIA P.f.& Pan Ag Rapid Test Kit


Cassette

CareStart™ Malaria/Pregnancy Combo (pLDH/HRP2/HCG)

GO221 Access Bio, Inc.

Cassette

CareStart™ Malaria HRP2/pLDH (Pf/PAN) COMBO

G0131 Access Bio, Inc.

Cassette

8




A B C D

CareStart™ Malaria pLDH 3 Line Test GO121 Access Bio, Inc.

Cassette

CareStart™ Malaria Screen GO231 Access Bio, Inc.

Cassette

Clearview® Malaria Combo VB11 Vision Biotech (Pty) Ltd √ Cassette

Clearview® Malaria Dual Test Device VB20 Vision Biotech (Pty) Ltd √ Cassette

Core Malaria Pan Pf MAL-190024 Core Diagnostics Ltd.

Cassette

diagnosticks MALARIA (Pan/Pf) Cassette

MPNFWBC1007.4 SSA Diagnostics & Biotech Systems

Cassette

EzDxTM Malaria Pan/Pf Rapid Test Detection kit

RK MAL 001 Advy Chemical (Affiliate of Bharat

Serums & Vaccines Ltd. ) Cassette

First Response® Malaria pLDH/HRP2 Combo Test

I16FRC30 Premier Medical Corporation Ltd. √ Cassette

FirstSign™ - ParaView (Pan+Pf) Malaria Test

2101 CB-25 Unimed International Inc. √ Cassette

Hexagon Malaria Combi 58024 Human GmbH

Cassette

HiSens Malaria Ag P.f/P.v Card HR2823 HBI Co., Ltd.

Card

HiSens Malaria Ag Pf/Pv (HRP2/pLDH) Card

HR2923 HBI Co., Ltd.

Card

Humasis Malaria P.f/Pan Antigen Test AMAL-7025 Humasis, Co., Ltd.

Cassette

ICT Diagnostics Malaria Combo ML02 ICT Diagnostics √ Cassette

ICT Diagnostics Malaria Dual ML03 ICT Diagnostics

Cassette

IMMUNOQUICK CONTACT MALARIA +4

0525K25 Biosynex

Cassette

9




A B C D

Immunoquick Malaria +4 0506_K25 Biosynex

Dipstick

IND ONE STEP MALARIA ANTIGEN P.f/Pan TEST

535-10 IND Diagnostics Inc.

Cassette

Malaria Pf/ PAN GM004 Genomix Molecular Diagnostics

Pvt.Ltd. Cassette

Malaria pf (HRP II)/PAN (pLDH) Antigen Detection Test Device

1-13-101-1 United Biotech, Inc.

Cassette

Malaria P.F/Vivax 17211OP-25 Diagnostics Automation/ Cortez

Diagnostics, Inc Cassette

Malaria Pan Test MAL-W23N-001 Dima • Gesellschaft für

Diagnostika mbH Cassette

Malaria pf (HRP II) / (PAN-pLDH) Antigen Detection Test Device

MFV-124R AZOG, Inc. √ Cassette

Malaria pf (pLDH) / PAN-pLDH Test Device

MFV-124 AZOG, Inc.

Cassette

Malascan™ Device - Rapid test for Malaria Pf/Pan

50402025 Zephyr Biomedical Systems √ Cassette

Maleriscan® Malaria P.f/PAN (Pv, Pm, Po) 3 Line Antigen Test

MAT-PF/PAN-50 Bhat Bio-Tech India (Pte.) Ltd.

Cassette

MeDiPro Malaria Ag HRP2/pLDH Combo

IR-0051K Formosa Biomedical Technology

Corp. Cassette

NanoSign Malaria Pf/Pan Ag RMAP10 Bioland, Ltd √ Cassette

NanoSign Malaria Pf/Pv Ag - RMAD10 Bioland, Ltd

Cassette

One Step Malaria Antigen Strip 820-1 IND Diagnostic Inc.

Dipstick

One Step Malaria P.f/Pan Test W56-C Guangzhou Wondfo Biotech Co.

Ltd. √ Dipstick

OnSight™ – ParaQuick (Pan, Pf) Test 536-25DB Amgenix International, Inc.

Cassette

10




A B C D

OnSite Pf/Pan Malaria Ag Rapid Test R0113C CTK Biotech, Inc. √ Cassette

OptiMAL-IT 710024 Diamed - A Division of Bio-Rad √ Hybrid

ParaHIT - Total Ver. 1.0 (Dipstick) 55IC203-10 Span Diagnostics Ltd.

Dipstick

ParaHIT - Total Ver. 1.0 (Device) 55IC204-10 Span Diagnostics Ltd.

Cassette

ParaHIT® total (dipstick) 55IC201-10 Span Diagnostics Ltd

Dipstick

Parahit-Total Device Rapid test for P. falciparum and Pan malarial species

25989 Span Diagnostics Ltd.

Cassette

Parascreen™ Device - Rapid test for Malaria Pan/Pf


Quickstick Malaria Antigen Test -- Innovatek Medical Inc.

Dipstick

SD BIOLINE Malaria Ag P.f/Pan 05FK60 Standard Diagnostics Inc. √ Cassette

SD BIOLINE Malaria Ag Pf/ Pan 05FK66 Standard Diagnostics Inc.

SD BIOLINE Malaria Ag 05FK40 Standard Diagnostics Inc. √ Cassette

Surestep™ Easy Malaria Pf/Pan Rapid Test Device

IMA-T402 ACON Biotech (Hangzhou) Co. Ltd.

Cassette

Pf and Pv

Advanced Quality™ One Step Malaria P.f/P.v Tri-Line Test

ITP11003 TC40 InTec Products, Inc.

Cassette

Advantage Malaria Card IR211025 J. Mitra & Co. Pvt. Ltd.

Card

BIONOTE MALARIA P.f.& P.v. Ag Rapid Test Kit


Cassette

11




A B C D

CareStart™ Malaria HRP2/PLDH (Pf/Pv) COMBO

G0161 Access Bio, Inc. √ Cassette

CareStart™ Malaria HRP2/PLDH (Pf/VOM) COMBO

G0171 Access Bio, Inc. √ Cassette

Core™ Malaria Pv/Pf MAL-190022 Core Diagnostics

Cassette

diagnosticks- Malaria (Pv/Pf) Cassette KMVFC6002 SSA Diagnostics & Biotech Systems

Cassette

Falcivax Rapid Test for Malaria Pv/Pf (device)

50300025 Zephyr Biomedicals √ Cassette

FirstSign™ – ParaView-2 (Pv + Pf) Card Test

2102CB-25 Unimed International, Inc.

Cassette

HiSens Malaria Ag P.f/P.v Combo Card


Cassette

HiSens Malaria Ag P.f/VOM Combo Card


Cassette

Humasis Malaria P.f/P.v Antigen Test AMFV-7025 Humasis, Co., Ltd.

Cassette

Malaria Pf/Pv GM002 Genomix Molecular Diagnostics

Pvt.Ltd. Cassette

Malaria pf (HRP II) / pv (pLDH) Antigen Detection Test Device

1-13-101-3 United Biotech, Inc.

Cassette

Malaria pf (HRP II) / pv (pLDH) Antigen Detection Test Device

MFV-124V AZOG, Inc.

Cassette

Maleriscan® Malaria Pf/Pv MAT-50 Bhat Bio-Tech India (P) Ltd

Cassette

Medisensor Malaria HRP2/pLDH (Pf/Pv) COMBO

M161 Medisensor, Inc.

Cassette

Medisensor Malaria HRP2/pLDH (Pf/VOM) COMBO

M171 Medisensor, Inc.

Cassette

OnSight™ - ParaQuick-2 (Pv,Pf) Malaria Test

537-25-DB Amgenix International, Inc.

Cassette

12




A B C D

OnSite Malaria Pf/Pv Ag Rapid Test R0112C CTK Biotech, Inc. √ Cassette

One Step Malaria P.F/P.V Test (Cassette)

523352 Blue Cross Bio-Medical (Beijing)

Co., Ltd. Cassette

ParaCare Malaria HRP2/pLDH (Pf/Pv) COMBO

G0161 Access Bio Ethiopia

Cassette

ParaCare Malaria HRP2/pLDH (Pf/VOM) COMBO

G0171 Access Bio Ethiopia

Cassette

RAPID 1-2-3® HEMA CASSETTE MALARIA PF/PV TEST

MAL-PFV-CAS/25(100)

Hema Diagnostic Systems, LLC

Cassette

SD BIOLINE Malaria Ag Pf/ Pf/ Pv 05FK100 Standard Diagnostics Inc.

Cassette

SD BIOLINE Malaria Ag Pf/Pv 05FK80 Standard Diagnostics, Inc.

Cassette

TrustyTM Malaria Antigen P.f./p.v. test A03-12-322 Artron Laboratories Inc.

Cassette

Pf, Pv and Pan

Core™ Malaria Pan/Pv/Pf MAL-190026 Core Diagnostics

Cassette

diagnosticks MALARIA (Pan/Pv/Pf) Cassette

MPNVFC1007.5 SSA Diagnostics & Biotech Systems

Cassette

FirstSign™ - ParaView-3 (Pan+Pv+Pf) Malaria Test

2103 CB-25 Unimed International Inc.

Cassette

Paramax-3 Rapid Test for Malaria Pan/Pv/Pf (device)

50320025 Zephyr Biomedicals

Cassette

Pan only

Advantage Pan Malaria Card IR013025 J. Mitra & Co. Pvt. Ltd.

Cassette

AZOG hCG Malaria Detection Test Device

MPT-124 AZOG, INC.

Cassette

13




A B C D

CareStart™ Malaria pLDH (PAN) G0111 Access Bio, Inc.

Cassette

Clearview® Malaria pLDH 70884025 Orgenics Ltd. (Inverness Medical

Innovations) √ Cassette

diagnosticks MALARIA (Pan) Cassette MPNWBC1007.3 SSA Diagnostics & Biotech Systems

Cassette

First Response® Malaria Ag pLDH I12FRC30 Premier Medical Corporation Ltd.

Cassette

FirstSign™ - PanCheck (Pan) Malaria Test

2104 CB-25 Unimed International Inc.

Cassette

OnSight™ - PanScreen (Pan) Malaria Test

539-25-DB Amgenix International, Inc.

Cassette

Parabank™ Device - Rapid test for Malaria Pan


Pv only

SD BIOLINE Malaria Ag Pv 05FK70 Standard Diagnostics, Inc.

Cassette N/A

* Some production may include different catalogue numbers for different box sizes; contact manufacturers for detailed information. N/A Results not available Pan All Plasmodium species Pf Plasmodium falciparum Pv Plasmodium vivax