REQUEST FOR PROPOSAL. Development of POC HCV RNA assay on polyvalent fully integrated platform. Ref: FIND-HCRN-001. Released version: 14 February 2018

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1 REQUEST FOR PROPOSAL Development of POC HCV RNA assay on polyvalent fully integrated platform Ref: FIND-HCRN-001 Released version: 14 February 018 Issue date: 14 February 018 RFP closing date: 0 March 018 RFP closing time: 18:00 Central European Time FIND Campus Biotech Chemin des Mines 9 10 Geneva Switzerland T +41 (0) F +41 (0)

2 Title Request for Proposal (RFP) for the development of automated, fully integrated, point-of-care (POC) molecular diagnostic assay for hepatitis C (HCV) detection in resource-limited settings. Background FIND s HCV programme seeks to contribute to achieving the WHO targets for elimination of viral hepatitis. To this end, FIND is exploring new partnerships in the areas of Point-Of-Care (POC) testing for HCV to enable diagnosis and treatment scale-up. Separate RFPs will be issued to address individual diagnostic gaps. This RFP specifically focuses on developing an assay for detection of hepatitis C virus (HCV) RNA on a fully integrated cross-cutting platform that can be adapted for detecting multiple infectious diseases of interest to FIND s Global Health portfolio (TB, AMR, HIV, HBV). End goal would be to provide a comprehensive, sample in, clinically actionable results out integrated capability for use in Level 1 settings and would meet regulatory standards for approval by WHO and in targeted countries. The high-level product requirements for a POC virological test for HCV have been published in the form of a target product profile (TPP). A Product Requirements Document (PRD) that is specific for a POC HCV RNA test is included as an appendix to this RFP. Aim FIND invites developers that have a fully integrated cross-cutting POC molecular diagnostic platforms with the potential to meet the appended PRD to submit a proposal for the development of a virological molecular assay for HCV diagnosis. Relevant developers should have at least a working prototype of such a platform and have resources to complete its development and commercialization. FIND anticipates selecting 1- platforms for the feasibility evaluation stage, where the selected partner(s) will assess the feasibility of detecting HCV RNA on their platform (or prototype platform). This laboratory feasibility study will evaluate the analytical performance and operational characteristics of the diagnostic platform and the HCV RNA assay using clinical reference samples supplied by FIND. Results of the feasibility study will be assessed using pre-defined criteria and i

3 will inform a go/no-go decision for further investments in full scale assay development on one final selected platform. Objectives To develop and validate a test for HCV RNA detection on a low-cost, user-friendly, fully integrated cross-cutting POC platform that can be adapted for detecting multiple infectious diseases of interest to FIND s Global Health portfolio (TB, AMR, HIV, HBV). The objective of the feasibility study is to determine the platform and assay performance for the detection of HCV RNA. The following parameters will be evaluated: limit of detection, genotype inclusivity, clinical sensitivity and specificity using a reference panel of clinical specimens, time to test results. When relevant (i.e., if the platform employed in the feasibility study is in its final integrated form), operational characteristics such as ease of use and environmental requirements will also be assessed. Specific study end-points and success criteria will be defined and agreed upon by FIND and selected partners. Expected project duration The entire project, i.e. the feasibility and assay development is expected to last years. The expected duration of the feasibility study should be 4 months, which includes an initial assay development phase, followed by a performance evaluation study. We propose an upfront phone discussion in case of longer timelines. Specific timelines for further platform and assay development, and clinical evaluation will be discussed with the final selected partner after successful completion of the feasibility study. Study design Support provided The feasibility study is a laboratory study performed at the platform provider facilities using synthetic HCV RNA, HCV-positive and HCVnegative plasma specimens and spiked whole blood specimens. Specifics of the study plan will be jointly developed by FIND and the selected partner(s). For the feasibility study, FIND will provide: ii

4 1. Funding to cover the personnel and material expenses incurred by the developer for HCV RNA assay development (up to 150,000 US$).. Reference samples for assay development and the performance evaluation study.. Time and effort by FIND personnel and consultants as needed to support the study. This time includes technical assistance during the assay development in order to optimize and integrate plasma sample preparation. During the development phase FIND will provide further financial and technical support including funds for product development (up to M US$). If product development and validation is completed within years, FIND will design and conduct clinical trials in line with CE IVD/WHO PQ requirements. Specific levels of funding and levels of supports will be discussed at a later time. Success criteria Primary outcomes (Feasibility study) Secondary outcomes (Feasibility study) FIND has defined key platform and assay attributes that should serve as success criteria (Appendix I: PRD). Minimal and optimal requirements have been defined for each success criterion. Success criteria do not all have the same importance or prioritization. Key criteria with rating for prioritization (Appendix I) will be reviewed based on information submitted by the organization and must be addressed during the laboratory feasibility study. Demonstrated capability of assay and platform to meet the success criteria Selection of platform partners for the subsequent phases of the project, which include further product development and clinical evaluation Validated protocols for sample preparation that is integrated/has a high potential to be integrated to the platform A written report describing the methods employed and the results of the laboratory feasibility study The generated (raw and analysed) data from the evaluation of the platform for the detection and quantification of HCV RNA, based on the success criteria iii

5 Confidentiality Significance Expected proposal content Submission Deadline FIND considers any proposal received under the RFP as confidential. If required FIND can sign a Confidential Disclosure Agreement (CDA) with interested organizations prior to proposal submission. FIND will not disclose the proposal to third parties without the prior written agreement of the proposal submitter. The review of proposals will be carried out by a team comprising internal FIND experts and independent external experts. External reviewers are under confidentiality agreement and are recused if found to have a potential conflict of interest (which they are obliged to disclose). Any specific questions concerning confidentiality should be addressed to the FIND team. The availability of a POC test for HCV RNA would greatly simplify the algorithms for HCV diagnosis, catalysing an increase in diagnosis rates and treatment scale-up. This effort should ultimately contribute to the WHO targets on HCV for 00: 80% reduction in incidence, 65% reduction in mortality, and 80% of HCV+ individuals receiving treatment. Possibility to adapt the platform for diagnosis of other infectious diseases will allow to integrate HCV testing in other health services such as TB programmes, STI care, etc., and thereby expand access, enable demand aggregation and price reductions. Expected proposal content is described in Appendix III. Proposals in English are to be sent by to the project team (see contact details below). The deadline for full proposal reception is fixed as FRIDAY, MARCH 018 by CET. Selection process Proposals will be assessed and partners selected through a systematic process as described on the FIND website. The process is designed to be objective, independent, and transparent to ensure that the most suitable technologies are supported and potential conflicts of interest are avoided. Selection of partners for feasibility studies will be based on submitted data on analytical sensitivity and scoring of platform, assay and iv

6 organization-specific parameters with ranking as described in Appendix I and Appendix II. The project team will conduct site visits and/or phone discussions with shortlisted candidates. Evaluation of proposals will be conducted from 6 March until 17 April. If additional information or discussions are needed with any candidate during this window, the candidate(s) will be notified. FIND intends to select up to two candidate technologies for feasibility evaluation. This decision will be made no later than April 018. In parallel with the feasibility evaluation, in-depth due-diligence assessments of the partners will be conducted to inform down selection to one partner to take forward for full development. The assessment results along with feasibility data will be presented to the FIND SAC for final partner selection. This decision is expected to be completed before end of October 018. Contact FIND is available to further discuss this opportunity in a telephone conference and to answer questions via . Elena Ivanova, Elena.Ivanova@finddx.org, Senior Scientific Officer, HCV Programme Ranga Sampath, Ranga.Sampath@finddx.org, Chief Scientific Officer v

7 APPENDIX I: Key product requirements Each attribute will be scored as follows: Attributes with Optimal and Minimal Requirements 0: not met 1: minimal requirement met : promising: current version can be improved to meet optimal requirement : optimal requirement met Attributes with a single Requirement 0: not met : promising: current version can be improved to meet the requirement : met Attribute Optimal requirement Minimal requirement Rank 1 = desirable = important = crucial A. Platform requirements Target operator Community workers with minimal training Healthcare workers or laboratory technicians with limited training (i.e. able to operate an integrated test with minimal additional steps) Lowest setting for implementation Community centers (Level 0) Health clinics (Level I) Specimen type Blood, sputum, urine, stool Blood 6

8 Sample preparation Fully integrated sample-to-answer Integrated specimen preparation; not more than manual steps required (no precision volume control and precision time steps) Multiplexing Ability to measure -10 analytes (plus controls) and more. Ability to detect DNA and RNA in the same sample. Ability to measure at least analytes (plus controls). Types of analytes DNA, RNA, proteins DNA, RNA 1 Throughput Portability Multiple at a time (without batching). Random access/parallel processing Small, portable or hand-held, device, 5 kg One at a time 1 Small table-top device Power supply/battery Battery-operated with recharging solution (e.g. solar) and circuit protector lasting up to days of constant use; and able to run off standard electricity (i.e. Local AC mains power) Rechargeable battery or solar power lasting at least 8 hours; and able to run off standard electricity (i.e. Local AC mains power) 7

9 Storage and operating environmental stability Between +5 to +40 o C at 90% humidity and at an altitude of 000 meters; Able to function in direct sunlight and low light; able to withstand dusty conditions Between +10 o to +5 o C at 70% humidity and at an altitude of 000 meters; Able to function in direct sunlight and low light; able to withstand dusty conditions Shipping and operating mechanical stability Durability System shall be designed to withstand typical handling during use, both before and after sample loading, including short delays. System shall be designed to pass shock and vibration tests as defined ISTA-A, ISTA-A and 6-FedEx. Instrument shall have a useful life of years or 0,000 tests in the field, be reliable (<10% failure rate) in all conditions of normal use throughout its life, and withstand regular cleaning with sterilization reagents. Maintenance Preventative maintenance should not be needed until after 1 year or > samples; only simple tools and minimal expertise should be required; an alert should be included to indicate when maintenance is needed. Quality control Proactive identification of error conditions and alert to the user in case of error. Compatible with some External Quality Assurance program or a developersupplied system for evaluating instrument and operator function. Internally controlled and/or calibrated. Data analysis Integrated data analysis (no requirement for PC) Data Storage Storage of all relevant operational and clinical data for every test; up to one month s test data. 8

10 Data export Export of all device and test data over integrated hardware. Export of data via GSMA SMS Data export encryption. Data export in HTTPs, XML, JSON, HL7. Configurable destination IP and DNS address. User initiated data export. Scheduled/automatic data export. Export of all device and test data over integrated hardware. Data export encryption. Data export in.csv file format. Configurable destination IP and DNS address. User initiated data export. Connectivity Integrated Local Area Network (LAN) port. Multi-band GSM chipset G, G, LTE. Integrated Bluetooth 5.0. Integrated WI-FI 80.11ac. USB.0. Internally designable static IP address. Support for DHCP issued IP addresses. Bi-Directional communication ability to update connectivity software stack Integrated Local Area Network (LAN) port. Integrated WI-FI 80.11b/g/n. USB.0 Internally static IP address. Support for DHCP issued IP addresses. Support for HTTPs and SFTP protocols. Ability to update connectivity software stack via USB.0 or LAN Instrument COGS* <500 USD >15,000 USD Manufacturing ISO 1485:016 compliant Regulatory Designed to comply with Common Specifications (as they will be defined in upcoming months, stemming from regulation EU 017/746) B. HCV ASSAY REQUIREMENTS Intended use 1. Diagnose HCV infection. Confirm active HCV infection after positive HCV serology test. To confirm cure upon treatment completion 9

11 Sample type Capillary whole blood Venous whole blood, plasma, serum Time to result 0 min <90 min Analytical sensitivity Clinical sensitivity <00 IU/mL <1000 IU/mL >99% >95% Analytical specificity (exclusivity) No cross-reactivity with endogenous substances and exogenous factors (e.g. HIV, HBV, HSV, EBV etc) Clinical specificity >98% Precision Coefficient of Variation (CV) < 10% at <00 IU/mL CV < 15% at 1,000 IU/mL Genotype inclusivity Ability to quantitate Sensitivity and specificity requirements met for genotypes 1 through 6 Quantitative Qualitative Disposable and reagents shelf-life No cold chain required. Stability at least 1 month at +5 to +40 C No cold chain required. Stability at least 1 months at +10 to +0 C Assay COGS* <7 USD <15 USD (*) COGS: cost of goods sold, ex-works (not including shipping and distribution margins) 10

12 APPENDIX II: Organization assessment criteria Criterion Description Scoring Rank 1 = desirable = important = crucial Strength of the team Based upon experience of the management team as well as key positions within R&D, manufacturing, product realization, quality 0: team has no experience and no track record 1: adequately experienced, complementary team but limited track record for this specific company : highly experienced, complementary team with track record in IVD development NA: not applicable UK: Unknown Product development capabilities Current capacity for IVD development (e.g. under ISO1485, in-house expertise of experts in relevant fields and track-record 0: no capacity or capabilities 1: capacity and experience in all relevant development fields, ISO1485 in place, including written operating procedures and phase-gate milestone review process : highly experienced product development in all relevant fields that resulted in marketable IVD products, written operating procedures and phase gate milestone review process NA: not applicable UK: Unknown Distribution capacity Based upon current system for distribution and the extent of current capabilities 0: no capacity or capabilities 1: distribution channels exist, but only in the western world or in few LMICs : distribution channels exist in many LIMIC countries of interest (LMIC s in Africa, Asia, South America) NA: not applicable UK: Unknown xi

13 Manufacturing expertise/ capacity Current capacity of manufacturing lines, infrastructure for expansion; how close is the proposed solution to current commercialized products 0: no capacity or capabilities 1: capacity and experience but would have to expand production capabilities to meet projections beyond the study phase : capacity to meet needs for volume production (>1 M p.a.) for the product target NA: not applicable UK: Unknown Quality system and regulatory strength Certifications, extent of quality systems and experience in regulatory requirements 1: no quality system or regulatory experience : quality system (e.g. ISO1485) in place with documented evidence of utilization (CE marking) :full FDA, Koseisho, or CE compliant Quality System Regulation (QSR) with audit experience and experience in product registration worldwide (e.g. BRICS) NA: not applicable UK: Unknown Technology maturity and time to market Technology maturity and length of time it takes until the platform is available 1: low: (low) time to market >5 years, platform is in early concept phase : middle: time to market - 5 years (proof-of-concept done and test validated, initial clinical studies for similar analytes) : high: time to market for the target product < years (clinical studies with the target product for similar analytes) NA: not applicable UK: Unknown 1 xii

14 Co-funding Availability of internal/alternative external resources to complete platform development, commitment to take the product to the market 0: product is likely low priority for the organization 1: company is interested but have no internal resources to invest in the platform/assay development : high: strong interest in global health market, company showed its commitment, has resources and is interested to invest. NA: not applicable UK: Unknown Company business model Is the company s business model compatible with global health 1: low: mostly not : middle: neutral : high: mostly positive aspects NA: not applicable UK: Unknown xiii

15 APPENDIX III: Expected Proposal Content Recommended length: pages. Supplementary information can be included as appendices. Executive Summary (1/ page) Organization (1- pages) Brief history of the company and key achievements in the context of the project Total number of employees. Leadership team Total number of employees Annual financial turnover Technology (- pages) Principles of operation Stage of development of the POC platform. Current timeline to commercialization. Brief description of target assay that will be commercialized. Availability of funding to complete the development of the platform Freedom-to-operate (IP and IP licenses related to the project) Platform characteristics (- pages) Detailed status of the platform with regards to combining sample preparation and detection modules into an automated, fully integrated platform. Detailed status of the platform with regards to analytical sensitivity and dynamic range (please mention type of analytes and sample types tested to date, and include supporting data). Target operator and intended setting for implementation Type and volume of patient samples currently validated on the platform Portability Power supply requirements Multiplexing capabilities Data analysis and data storage capabilities Instrument and assay COGS Any supporting information on potential to meet the Key Product requirements listed in Appendix I (can be included as a supplement) Business & Operations (1- pages) Geographic presence Current capacity for IVD development, locations of facilities and subsidiaries relevant to the project Outsourced activities relevant to the project A high-level description of the commercialization strategy for the diagnostic test, covering in particular manufacturing and distribution aspects for low- and middleincome countries, as well as cost estimates of the platform and assay xiv

16 Any supporting information that would facilitate scoring of the Organization Assessment Criteria listed in Appendix II. Feasibility study (- pages) Workplan and timeline Budget (including self-funding/ in-kind contributions from the POC platform provider, if any) Material, reagent, and sample requirements List of key personnel expected to be involved in the project and a summary of their relevant expertise (please, include a summary in the main text of the proposal and a bio sketch in the appendices) Project risks xv