Preclinical Validation of a Novel Injection-Molded Swab for the Molecular Assay Detection of SARS-CoV-2

Abstract

During the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers have timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including collection swabs, has helped to expand the availability and capability for various diagnostic, therapeutic, and protective medical devices in high demand during the COVID-19 emergency. Here, we report the initial validation of a new injection-molded anterior nasal swab, ClearTip™, that was experimentally validated in a laboratory setting as well as in independent clinical studies in comparison to gold standard flocked swabs. We have also developed an in vitro anterior nasal tissue model which offers a novel, efficient, and clinically relevant validation tool to replicate the clinical swabbing workflow with high fidelity, while being accessible, safe, reproducible, and time- and cost-effective. ClearTip™ displayed greater inactivated virus release in the benchtop model, confirmed by its greater ability to report positive samples in a small clinical study in comparison to flocked swabs. We also quantified the detection of biological materials, as a proxy for viral material, in multi-center pre-clinical and clinical studies which showed a statistically significant difference in one study and a reduction in performance in comparison to flocked swabs. Taken together, these results emphasize the compelling benefits of non-absorbent injection-molded anterior nasal swabs for COVID-19 detection, comparable to standard flocked swabs. Injection-molded swabs, as ClearTip™, could have the potential to support future swab shortages, due to its manufacturing advantages, while offering benefits in comparison to highly absorbent swabs in terms of comfort, limited volume collection, and potential multiple usage.

In Vitro Nasal Tissue Model for the Validation of Nasopharyngeal and Midturbinate Swabs for SARS-CoV-2 Testing

“…This has also been shown in other studies, where injection molded swabs pick up significantly less mucus with a more efficient release than flocked swabs. 4 , 5 …”

“… 3 Compared to a standard flocked, the injection-molded swabs are characterized by a nonabsorbent head and have demonstrated a more efficient release of viral RNA while absorbing less solution. 1 , 4 , 5 As a result, several prototypes of injection-molded swabs have been recently commercialized, including nasopharyngeal and midturbinate swabs like the IM2 and Rhinostic swabs. 3 , 4 These new one-piece specimen collection swabs can be efficiently mass produced without multistep manufacturing methods and postprocessing.…”

“…Therefore, we hypothesize that the initial validation of swab prototypes on a simplified, reliable, and physiologically relevant in vitro nasal tissue model would provide more consistent and reproducible results, allowing investigators to assess swab performance in a time- and cost-efficient manner. 5 , 10 Expanding the preclinical evaluation based on an in vitro tissue model will further support clinical studies to assess swab efficacy, streamlining the overall validation process.…”

“…The rapidly increasing demand for COVID-19 testing since the start of the 2020 pandemic has caused significant bottlenecks in testing capacity due to a global shortage of testing supplies, including specimen collection swabs. , To help overcome the swab shortage, alternative swabs that could be mass produced at a relatively low cost (e.g., via injection-molded processing) have been recently developed and raced to the market . Compared to a standard flocked, the injection-molded swabs are characterized by a nonabsorbent head and have demonstrated a more efficient release of viral RNA while absorbing less solution. ,, As a result, several prototypes of injection-molded swabs have been recently commercialized, including nasopharyngeal and midturbinate swabs like the IM2 and Rhinostic swabs. , These new one-piece specimen collection swabs can be efficiently mass produced without multistep manufacturing methods and postprocessing. Validation for swab prototypes typically requires preclinical testing before transitioning to clinical studies, which can take months to years.…”

“…Bench-top studies are performed by dipping in saline solutions without mimicking any of the physiological aspects of the nasal passage (i.e., architectural, mechanical, and physical structures) or of the actual swabbing procedure. , Other alternative modes of validation for prototype swabs in the preclinical phase include swabbing the cheeks of participants and quantifying bacterial and cellular uptakes in comparison to the standard swabs or through clinical studies. ,, By solely relying on clinical studies, even for preclinical validation, the swabs meet a great deal of variability, thus there is a need to expand participant enrollment, with a significant increase in associated time and costs. Therefore, we hypothesize that the initial validation of swab prototypes on a simplified, reliable, and physiologically relevant in vitro nasal tissue model would provide more consistent and reproducible results, allowing investigators to assess swab performance in a time- and cost-efficient manner. , Expanding the preclinical evaluation based on an in vitro tissue model will further support clinical studies to assess swab efficacy, streamlining the overall validation process.…”