Introduction and Background of the Project

Introduction

Tuberculosis (TB) is the number one infectious disease killer in the world. It kills more people than HIV, and is the most common cause of death for people living with HIV. In 2016, 374,000 HIV-positive people died from TB. But TB is curable, and most deaths from TB can be prevented with early diagnosis and treatment. Most commonly, TB diagnosis is made based on sputum analysis. However, data show that 20–60% of HIV-positive patients presenting for TB diagnosis are unable to produce a sputum sample. Lack of sputum and a true point-of-care test means that many patients cannot be diagnosed in time which results in high morbidity and the high mortality.

A urine sample is more easily accessible. The novel TB test co-developed by FIND (Geneva, Switzerland) and Fujifilm (Tokyo, Japan) is a rapid diagnostic test that detects low concentrations of LAM-antigen in the urine of people with TB/HIV co-infection. Preliminary data generated in hospitalized patients with HIV found the novel test to be >70% sensitive and >95% specific. – meaning TB can be correctly detected in 70% infected people within 1 hour.

Project objective

The ultimate goal of the project is to launch Fujifilm SILVAMP TB LAM as an IVD product and achieve WHO recommendation to use the test for TB diagnosis in HIV+ patients in LMICs.

Project design

Fujifilm’s and FIND’s project aims to (a) transfer Fujifilm SILVAMP TB LAM to volume manufacturing, (b) register the test as CE-IVD marked product, and (c) perform the analytical, clinical and operational studies to generate the required evidence for WHO policy development.

How can your partnership (project) address global health challenges?

The diagnostic gaps in TB, particularly in HIV-coinfected patients, remain greater than for any other infectious disease of poverty. The rapid, affordable, sensitive and urine-based Fujifilm test intends to fill this gap. Modelling shows that the test will have a high impact when combined with instantaneous, same-day treatment of TB patients with HIV co-infection, which is a patient group with very high mortality in the absence of a rapid intervention.

What sort of innovation are you bringing in your project?

The only commercially available tuberculosis point-of-care lateral flow test has suboptimal sensitivity which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM test was designed to achieve superior diagnostic accuracy. The novel assay combines high affinity monoclonal antibodies and Fujifilm’s innovative silver-amplification that increases the visibility of test and control lines. This enables the detection of approximately 30-fold lower concentrations of urinary LAM compared to conventional lateral flow immunoassays which results in significantly higher clinical sensitivity.

Role and Responsibility of Each Partner

Fujifilm will be responsible for regulatory approval of the product and to scale-up manufacturing to ensure the availability of sufficient numbers of kits for the clinical studies and the product launch. Fujifilm will further lead the refinement and implementation of the launch strategy in close collaboration with FIND.

FIND will be the overall coordinator of the project, responsible for establishing project goals and project management, monitoring and reporting on progress and performing the clinical studies using its well-established clinical trial platform with study sites in low and middle income countries. FIND will then present the body of evidence to the WHO for policy development.

Final Report

1. Project objective

Fujifilm and FIND have been working together since 2015 to develop a sensitive POC test to diagnose TB from urine. The targeted test should enable early treatment initiation, decrease mortality, and cut transmission.

The first award (G2015-201), delivered the initial LAM prototypes (FUJI-SAI Rapid TB™); the current award aimed to optimize its design and generate evidence of its performance.

The second award supported product validation, establishing a manufacturing site that meets ISO 13285 and production at scale, and performing evaluation studies in the settings of intended use to generate evidence for WHO policy development.

2. Project design

The project was structured around the following objectives:

1. Finish the product validation, transfer the product to manufacturing and set-up production at the appropriate scale
2. Prepare and submit the dossier for regulatory approval for registration as CE-marked IVD and ensure compliance with Japanese export regulations.
3. Generate clinical, operational and impact data for WHO policy development (use of the FUJI-SAI Rapid TB™ product to diagnose TB in all HIV+ patients), secure product implementation.
4. Refining the commercialization strategy, including distribution channels, technical support, development of appropriate training materials and work on an in-country QA strategy

3. Results, lessons learned

Clinical evidence generation: Overall FujiLAM sensitivity (n=1624) was 54·8% and overall specificity was 85·1% against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% to 83·3%, and 75.0% to 96·5% (Rita Székely, 2022). However, in a post-hoc analysis the test accuracy significant varied between Fujifilm lots, and this issue was rectified by Fujifilm by optimizing the manufacturing process, thus this project was extended for a year. FIND and Fujifilm proposed to conduct a standalone clinical evaluation of this updated product “FUJIFILM SILVAMP TB LAM Ⅱ”.

Manufacturing: Lot-to-lot variation delayed the process to scale up manufacturing, and in Dec 2021 production line was launched in Vietnam. Updated design lock product “FUJIFILM SILVAMP TB LAM Ⅱ” production will start in April 2023 and undergo further verification and validation before approval for clinical use.

Commercialization strategy: Fujifilm prepared and submitted the dossier for regulatory approval for registration of the product as an IVDR device under CE-Mark and ensured compliance with Japanese export regulations. Fujifilm conducted market research with a contracted consultant and identified key persons in public and private sector in priority countries. Fujifilm has also been communicating with a potential distributor, which has a strong channel with HIV related hospitals. Fujifilm will develop a concrete strategy for market penetration once distribution agreement is made.