Q&A: Our biggest struggle to apply to win the Longitude Prize
Dr. Radha Rangarajan and her team at Vitas Pharma won Discovery Award seed funding last November to help propel their research, and inevitably their future application for the Longitude Prize. Creating a truly point-of-care (POC) test, however, has proven difficult. In this Q&A Radha explains why.
Can you tell us a bit about your background and story? How did you become involved in diagnostics?
Dr. Rajinder Kumar and I co-founded the drug discovery and development company, Vitas Pharma, in Hyderabad, India in 2011 with a focus on identifying novel antibacterials to treat highly drug resistant infections. About two years ago, we realised that the compounds we take to the market will have greater clinical benefit if patients’ needs can be identified using a reliable and sensitive laboratory test. So we decided to develop companion diagnostics for our compounds. That was really the genesis of the diagnostics work at Vitas.
Why did you apply for a Discovery Award?
We have adopted a molecular technology that allows us to identify whether certain bacteria are present or not in a sample, with a simple test that does not require special training or equipment. Our technology is an “amplification technology,” meaning that the test amplifies specific regions of DNA, and if they are visible then the sample is considered positive.
We are working on a prototype test and needed funds for validation. If laboratory validation met our criteria for further development, our plan was then to undertake the steps needed for registration with the appropriate regulatory agencies. The Discovery Award we received is helping fund the laboratory validation efforts.
What progress have you made since you won the Discovery Award?
Our test has gone through some design changes! We are now working on a panel of tests instead of a single test. Validation of the tests against clinical isolates is ongoing. We are also evaluating how low cost automation could be introduced into the test design.
What are the biggest challenges you face in meeting the criteria to apply for the Longitude Prize?
The biggest technical challenge for us is to make our test POC. Our test requires a clinical microbiology laboratory with some basic laboratory equipment. Our aim would be to automate the different steps in performing the test, including reading the endpoint and reporting the data, which would potentially make it POC.
What type of bacteria will your test identify and what will it diagnose?
When we started the project, we wanted a “pan bacteria test”. This is a test which would say if bacteria are present or not in a sample, in general. But we have learnt from consultations with clinical microbiologists and clinicians that the test must also identify the bacterial species and provide as much information as possible about drug resistance. Thus, we have now moved towards a panel of tests, rather than one test.
The range of bacterial species that show up in a clinical practice is quite large; to have a test which recognises every single one of them would be virtually impossible. So, we have picked the 8 most clinically relevant species for our panel of tests. We have also selected a set of resistance mechanisms that are critical to identify early.
“The bottom line is you can get high sensitivity, high specificity and speed, but it comes at a cost. A test that is sensitive, specific, rapid and affordable: I believe that is what we need.“
Are there any tests already being used along the lines of what you are developing? How is yours different?
The kind of tests routinely used across the world are phenotypic tests. This means you grow the organism, do a Gram stain, then use manual or automated systems to determine the sensitivity of the organism. All this can take 24-72 hours. There are also molecular tests performed in some laboratories. Depending on resources available to the hospital or clinic, these can be PCR-based (molecular tests that amplify specific DNA, but generally take more time than the tests we are developing). While these assays have higher sensitivity and specificity, the time taken to complete the assay is still not clinically meaningful, that is to say, it is not quick enough to affect the initial treatment that is given.
More recently, fully automated phenotypic tests which identify species and resistance mechanisms within 24 hours (depending on how fast the organism grows) were approved by the FDA in the USA. However, one must invest in a completely new instrument and software, and these costs would be too high for a poorly-resourced laboratory.
The bottom line is that you can get high sensitivity, high specificity and speed, but it comes at a cost. Low-cost tests are slow, so a gap remains. A test that is sensitive, specific, rapid and affordable: I believe that is what we need.
What is the significance of bridging that gap? What can be achieved and what is the impact?
The gap must be bridged as healthcare budgets across the world are stretched. The cost of the diagnostic must not be a barrier for adoption in the clinic. At the same time, the test must be meaningful from a clinical perspective. The physician needs many pieces of information to decide whether or not to prescribe an antibiotic, such as species, mechanism of resistance, bacterial count etc. The impact of a test that can actually put all of the pieces together in an affordable manner will be significant.
We have decided to think about our diagnostic test in a modular manner, creating a panel of tests that can give the physician a few critical pieces of information. We will continue building additional modules to enhance the capabilities of the test.
“We want to develop our test for global markets, with a particular focus on India. Our challenge is to optimise the test, so that it is both point-of-care and affordable.”
In what settings is your test expected to be used / in what clinical context? What might a patient present with and what could be applied?
The easiest clinical setting we can imagine right now is a hospital with a clinical microbiology laboratory. A patient might come in to the ICU and the physician wants a quick test to confirm or deny the presence of an infection, with an identification of the organism and its resistance to specific antibiotics. That is what our test is designed to do.
What is the turn-around time for your test currently?
Our test requires 1-2 hours depending on the sample type. We are trying to improve the sample handling procedure to reduce the time.
One criteria of the Longitude Prize is that your test must be affordable and available wherever needed. Where do you envisage your test in the world and what will the target market be?
We want to develop our test for global markets, with a particular focus on India.
Our challenge is to optimise the test, so that it is both POC and affordable. We are seeking a design that will be simple to manufacture and not increase the burden on the end user.
You have had other funding from BIRAC?
We have BIRAC grants for the discovery of novel antibacterials for Gram negative infections.
Our Q&As are edited in partnership with the interviewee for brevity and clarity.