In Vitro Diagnostics (IVD) Development in Times of the Corona-Crisis
by Maximilian Strunz
More than ever, in vitro diagnostic (IVD) tools are needed to expand our options in detecting and diagnosing viral-mediated diseases. With the spread of SARS-CoV-2 it became indispensable to track and predict the hotspots of the outbreak, and to monitor the virus and the mutants thereof. It is THE time for IVDs to demonstrate their benefits in diagnostic testing by providing essential information on the scale, location, and trajectory of the disease.
It is paramount to be able to evaluate the infection status of whole populations, including symptomatic patients and asymptomatic carriers, and to assess potential immunity of individuals who were at risk or exposed to the virus. While IVD advantages include quick results, simultaneous multiple testing, ease of data recording, or scalability, the main reason for superiority is the test reliability and repeatability .
Accurate testing is a prerequisite for coping with COVID-19, however, the development of IVDs against viruses is not a trivial endeavor. Since no diagnostic test can be a fit-to-all solution, the IVD test complexity of components and reagents, as well as the test tradeoffs should be attentively considered before its development [2,3]:
Speed – time frame from sample collection to final test result
Intended purpose – IVD target product profile
Instructions for use – reliable testing at scale
Accuracy – disease diagnosis without false-positive/false-negative results
(sensitivity and specificity assessment to avoid continuous spreading)
Input sample – sample source (oral/nasal swab, blood, sputum)
Costs/pricing – total test price, automation options, etc.
Up to date, the development of COVID-19 tests has ramped up massively. The rapidness of disease spreading and the urge to carry out large-scale testing, has led to the commitment of the diagnostic industry to concentrate its production and development capacities on one common goal. Despite the pace and urgent need, it remains critical to ensure a test’s reliability. Therefore, despite the high number of tests required to be readily available, developers need to ensure an in-depth quality control and quality assurance infrastructure to maintain accuracy and comparability [2,3].
To respond effectively to the outbreak, several test formats are currently available or in development: (a) molecular diagnostic tests useful for the detection of the virus, disease diagnosis and monitoring , (b) IgG- or IgM-based tests to assess potential immunity, or (c) tests to assess the viral load . Such tests would enable rapid, point-of-care testing, however, largely depend on validated specific antibodies, which extends their development time.
The reliability of all these test options is anchored in the reliability of their single components. Upon failure of one, virus-shedding carriers may be erroneously identified as virus-free. Therefore, both the IVD analytical and clinical performance needs to be defined through an appropriate validation strategy, batch release controls, and verification measures to ensure the reliability of the tests.
In April 2020, the European Commission (EC) has published guidance on conformity assessments and standards pertaining to IVD development during the COVID-19 pandemic. These guidelines are in line with the In Vitro Diagnostic Devices Directive 98/79/EC and the IVD Regulation 2017/746, and inform about harmonized standards and derogation procedures, including the development of test performance criteria and a strategic use of these test across the European Union .
In a press release, the EC has concluded that some entities developing IVDs had failed to meet expected standards . The report continues to state a “mismatch between the existing quality and what could be expected to ensure good performance of the tests” .
Although the EC concedes the need for a faster evolution of test options, it wants developers to be up to the speed while retaining state-of-the-art regardless.
Despite the advancements in this fast-moving field, it is critical to ensure the development of high-quality IVD tests. Best-in-class performance can only be achieved by well-advised strategic development plans and clearly pre-defined clinical and regulatory plans to result in successful approval.
At Biopharma Excellence, our specialists can help creating targeted development strategies and navigating performance validation for your products – from idea to regulatory approval. Contact us to speak with our experts!
Afzal, A. (2020). Molecular diagnostic technologies for COVID-19: Limitations and challenges. Journal of advanced research.