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Clinical Diagnostics: Development, Trouble-shooting & Validation

In the midst of the COVID-19 pandemic, there has been a lot of discussion in the media and among the scientific community about diagnostic testing aimed at the SARS-CoV-2 virus. Tackling a pandemic like we are currently experiencing takes an ‘all hands on deck’ approach to developing and validating new tests. Accurate diagnosis of COVID-19 patients obviously leads to proper care, but it also avoids the negative impact felt by ‘false positives’ in an already stressful situation. FDA issued “Policy for Diagnostic Tests…” on March 16, 2020 to guide clinical labs (CLIA labs), developers, and manufacturers in their efforts to quickly roll out accurate and specific clinical diagnostic tools.

Categorization of Clinical Diagnostic Tools: Principle Technology

FDA breaks new tests into three groups based on the “Principle Technology”:

  1. Molecular Diagnostics (tests for COVID-19 nucleic acid)
  2. Antigens (tests for viral particles)
  3. Serological (tests for antibodies, i.e. IgM and IgG)

New tests are should be evaluated to ensure analytical and clinical validity around the following:

  • Accuracy
  • Specificity
  • Sensitivity

For more information on FDA’s guidance for industry, check out FDA’s Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests.

How Avomeen Supports the Development, Trouble-shooting & Validation of Clinical Diagnostics

Avomeen is an independent cGMP/cGLP contract research and development organization supporting manufacturers engaged in the development, trouble-shooting, and validation of diagnostic tools for COVID-19 and other diseases. Some of the more common issues that we help our clients address include:

Clinical Accuracy

Tests need to be evaluated and validated using samples that have been verified to be COVID-19 positive by an orthogonal method. COVID-19 samples have been difficult to source, but Avomeen has found reliable sources to obtain samples for validation.

Cross-Reactivity

Cross-reactivity due to previous infections are highly common and should be assessed during a diagnostic method development and validation.

Interfering Substance

The sample must be evaluated for potential interference by common substances that can be found in nasal samples or serum samples, such as nasal sprays, anti-viral drugs, or the patient’s blood.

Specificity & Sensitivity

To determine specificity and sensitivity, the prospective diagnostic tests need to be screened with samples of known positive SARS-CoV-2 to make sure that non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, or 229E are not providing false positives or false negatives.

Identifying/Trouble-shooting

Sometimes impurities from diagnostic test itself (manufacturing process), or from the patient (matrix) can confound test results. Avomeen employs sensitive qualitative and quantitative biochemical and chemistry methods to identify interferences and guide further development efforts. In addition, specimen collection tubes can be subject instability which over time can affect a test’s validity. Avomeen can develop stability indicating methods and perform stability studies to ensure the test kit’s performance over time.

Commonly Used Tools & Techniques

Avomeen’s scientists frequently use:

  • Liquid Chromatography coupled with DAD, UV, ELSD, or MS Detection (purity of raw materials, constituents)
  • Liquid Chromatography coupled with an analytical fraction collector
  • Mass Spectrometry (QToF, or MS/MS) (identification of contaminants and low level constituents)
  • Capillary Electrophoresis (purity and characterization of biomolecules)
  • Immunoassays
  • SDS-PAGE
  • Cell culture
  • UV and Fluorescence Plate Reader (high throughput assessment of biochemical assays)

Our team is standing by to help you bring your diagnostic test to the clinic. Get in touch with us for a quick response and turnaround.

 

Our expert blogger is Dr. Khanh Ngo Courtney, Avomeen’s Project Director of Biologics. She provides clients with unparalleled expertise and tactical knowledge of protein biochemistry and molecular biology. Her experience extends from R&D to analytical method development, validation, implementation, method transfer, and optimization of test methods for the cGMP setting per USP and ICH guidelines. This understanding of the entire process helps guide successful and productive collaborations across different laboratories, sites, and functions.

Learn more about Khanh’s expertise and experience.