COVID-19 Nasal Swabs | NIH 3D Print Exchange

Background

Many stakeholders have expressed interest in the manufacturing and use of non-traditional swabs (e.g. 3D printed swabs) for collecting specimens (e.g. nasopharyngeal) for COVID-19 diagnosis to meet the increasing demands for swabs. Additionally, questions regarding the safety and effectiveness of non-traditional swabs have been raised by manufacturing, clinical, and regulatory communities in many countries.

One concern is that 3D printed swabs may be prone to breaking; this concern has arisen from reports of brittle 3D printed swabs that have broken through shipping or handling, causing unintended sharp edges on these products. It is hypothesized that steam sterilization may contribute to this problem, and thus is it essential to evaluate the physical properties of these products after sterilization . A second concern addresses the effectiveness of 3D printed swabs in capturing sufficient sample from the appropriate anatomic site and the compatibility of these swabs in downstream diagnostic assays. Many of the 3D printed swabs use non-traditional capture geometries. Some studies assessing non-traditional swabs have provided useful but limited data on the effectiveness of nasopharyngeal swabs for COVID-19 diagnosis in clinical settings.

Through multiple discussions across the Federal Government, with key stakeholders, and experts in the community who have evaluated 3D printed swabs, it appears that non-traditional swabs pose unique technical aspects not present in other types of swabs currently on the market; these technical aspects should be considered when evaluating safety and effectiveness.

A combination of the following considerations may be valuable to provide consistency in developing and validating 3D printed swabs for clinical use. Relevant performance standards are provided below.

Development and Manufacturing Community

The development of a 3D printable swab may follow the considerations laid out in the FDA Guidance “Technical Considerations for Additive Manufactured Medical Devices,” specifically: material controls, post processing and overall process validation. Taken together, all these items could be evaluated as a part of the quality system requirements and to account for the process variability that is unique to 3D printing. All Quality Management System requirements should be in place prior to manufacturing a final product that will be sold to the end user for patient specimen collection. The swab could be manufactured from materials with a history of safe use; the material could be verified to be non-cytotoxic, non-irritating, and non-sensitizing, as well as compatible with testing assays.

Analytical Studies

Several key elements could be considered in analytical studies. The analytical study descriptions are aimed at demonstrating the ability of 3D printed swabs to sufficiently collect, retain and elute clinical specimens and be compatible with (and not negatively affect) representative downstream in vitro diagnostic tests (e.g., polymerase chain reaction (PCR), or antigen). Analytical studies could provide data (using SARS CoV-2 or similar viruses) that demonstrates the swab can collect and elute viral sample (spiked into a control sample), and not interfere with downstream assays (e.g. molecular (PCR) or antigen testing).

Material testing may include the following, but not be limited to:

Testing to be performed on product post-sterilization to ensure the testing is representative of the material in the final finished device.

Biocompatibility testing for cytotoxicity, Irritation and sensitization (per ISO 10993-1). Biocompatibility studies would demonstrate the swab to be safe for limited contact.

These studies could demonstrate that the 3D swab performs equivalently (mechanical properties, flexibility, durability after sterilization) to traditionally manufactured swabs that are currently on the market and previously determined to be safe and effective. While there are no current test standards for swabs, existing test standards such as ASTM D638 (tensile testing), ASTM D1043 (torsional testing), and ASTM D6272/D790 (flexural testing) could be used as inspiration to assess the swab’s mechanical properties compared to traditionally manufactured swabs.

Testing could demonstrate equivalent performance of the subject non-traditional swab to traditionally manufactured swabs that are currently on the market for collection from the same specific target (e.g. nasal, nasopharyngeal, oropharyngeal) site. Such testing could demonstrate 95% positive and negative agreements of assay results (e.g. PCR).

The manufacturer may conduct any additional analytical testing that they determine to be valuable by providing scientific data in support of the non-traditional swab. Testing can demonstrate collection efficiency and the swab’s ability to function as intended in sampling from the specific anatomical site the manufacturer claims.

Clinical Testing

Clinical testing could demonstrate that the non-traditional swab can adequately collect clinical specimens without damaging tissue to an extent comparable to traditionally manufactured swabs used on the same anatomic site. It is common practice that appropriate clinical testing would aim to include a minimum of 30 positive samples and a minimum of 30 negative samples. The testing could be conducted in a parallel study design to compare the non-traditional swab to a swab that is currently on the market for collection from the target sample site (e.g. nasal, nasopharynx) and comparative testing using a downstream assay (e.g. molecular (PCR) or antigen detection). The subject non-traditional swab may optimally have equivalent performance to the comparator swab and should meet a minimum performance of 95% Positive percent agreement and a Negative percent agreement of 95%. Given the small sample size, it is expected that the 95% CI may be low.

Sterilization and Packaging

At this point, it is believed that sterile swabs are critical to avoid microbial infections in patients and maintain integrity of upper respiratory clinical specimens for subsequent in vitro diagnostic testing. Sterilization would be conducted and/or the sterilization process would be validated by the manufacturer prior to distribution. This may include an adequate number of swabs and different lots sampled, maximum parameters to ensure adequate sterilization, and bioburden testing of final product. Packaging of the sterile sleeve would address seal strength and packaging integrity in the context of shipping.

Labeling

Swabs would be labeled appropriately for their intended use, including what the swab is designed for and the site it is intended to sample [e.g. nasal (NS) or nasopharyngeal (NPS) specimens]. Labeling would include:

Specify the swab is provided as an absorbent tipped applicator, sterile, individually packed for single-use only and for use during the COVID-19 public health emergency. It would provide a description of the material and its characteristics.

Make clear recommendations to sufficiently reduce any potential risks for use. Examples include, but are not limited to, a caution against use of non-sterile product and recommendations for healthcare providers to visually inspect products for physical integrity prior to use.

Include a clear description of the available validation data for the device.

COVID-19 Supply Chain Response: 3D-Printed Nasal Swabs