Testing devices for COVID-19: Test swabs safety and effectiveness guidance

Background

COVID-19 is an infectious disease caused by the SARS-CoV-2 coronavirus. The World Health Organization declared a global pandemic in March 2020. The Minister of Health signed the Interim Order Respecting the Importation and Sale of Medical Devices for Use in Relation to COVID-19 on March 18, 2020. The interim order (IO) allows us to quickly address large-scale public health emergencies, such as through faster authorization of medical devices for COVID-19.

This guidance document presents the criteria for safety and effectiveness that apply to test swabs used for COVID-19 sampling. It also provides guidance on how to meet these criteria in an application under the IO pathway.

Diagnostic testing is a key element in both:

  • identifying cases of infection
  • preventing the spread of the coronavirus

A test swab may be used to collect a sample for either Polymerase Chain Reaction (PCR) laboratory testing or point-of-care testing. Point-of-care testing can be done directly in a hospital or doctor’s office.

Once the sample has been taken, the swab is either placed:

  • in a preserving liquid and sent to a laboratory for testing or
  • placed directly in a testing device (point-of-care)

Swabs may be packaged in a variety of virus transport media (VTM). Specifications for individual VTMs are beyond the scope of this document.

Swabs play a role in the accuracy of COVID-19 diagnostic testing. For example, false negatives can occur in PCR tests if:

  • the swab material inhibits the test reaction or
  • the swab design doesn’t provide enough surface area to obtain a sufficient sample

Test swabs that are not safe and effective may cause or lead to harm. For example:

  • a swab that breaks during sample collection can cause physical injury
  • a non-sterile swab that produces an incorrect test result can lead to harm

Swab manufacturers are encouraged to submit evidence of safety and effectiveness for IO authorization.

We are processing applications as quickly as possible. To avoid delays, please ensure you have completed your application properly. Please see our guidance document for more information on how to prepare applications submitted under this IO.

Medical Devices Regulations (MDR) classification

In the Canadian regulatory framework, Class I devices present the lowest potential risk and Class IV the highest. Swabs are classified according to their labelling and intended use.

For example, if a swab is labelled for nasopharyngeal (NP) or oropharyngeal (OP) use only, it is classified as a Class I medical device. See Classification Rule 2(2) of the MDR.

If a swab is not solely for use in oral or nasal cavities or its use is not explicitly stated, it is classified as a Class II device. See Rule 2(1). These swabs may be used to collect tissue samples (for example, to test for chlamydia or ureaplasma) from other body orifices. This use is associated with greater risk.

Under Rule 2:

  • Subject to subrules (2) to (4), all invasive devices that penetrate the body through a body orifice or that come into contact with the surface of the eye are classified as Class II.
  • A device described in subrule (1) that is intended to be placed in the oral or nasal cavities as far as the pharynx or in the ear canal up to the ear drum is classified as Class I.

Regulatory pathways for COVID-19 devices

Manufacturers of Class I swabs may seek authorization to import and sell their products under either:

  • a Medical Device Establishment Licence (MDEL)
    • MDEL is an establishment oversight framework that is not product-specific and is intended to strengthen post-market safety to mitigate risks
  • an IO authorization
    • product-specific safety and effectiveness information is required as part of pre-market applications

Health Canada is encouraging a sub-group of swab manufacturers to use the IO authorization pathway for Class I swabs, especially if they are:

  • new to the manufacturing of swabs and manufacturing in Canada, such as a company that has re-tooled to manufacture, or
  • using a new manufacturing process or design for swabs, such as 3D printing or a honeycomb design

IO applications for swabs should include the following information.

Device description

The device description should include:

  • a picture and/or engineering drawing
  • identification of all materials used to produce the swab
  • the intended use (for example, NP swabs)

Quality manufacturing

Manufacturers must either:

  • demonstrate compliance with quality manufacturing systems (for example, ISO 13485 certificate) applicable to the swab or
  • describe clearly the planned quality manufacturing systems that are consistent with similar existing manufacturing systems

Design verification

Provide swab design verification (bench testing) data in a summary report. It should show that the essential minimum design characteristics are met. These data should be based on test samples representative of finished swabs that have been sterilized before bench testing.

Dimensions

Swabs should have minimum length specifications and minimum and maximum head diameter specifications in order to be safe and effective:

  • minimum length specification
  • for example, adult NP swabs require ≥14 cm to reach the posterior nasopharynx
  • minimum and maximum head diameter specification
  • for example, adult NP swabs require 1 mm to 4 mm to pass into the mid-inferior portion of the inferior turbinate and maneuver well

Flexibility

Swab flexibility is assessed through:

  • durability
    • for example, tolerate 20 rough repeated insertions into a 4 mm inner diameter clear plastic tube curved back on itself with a curve radius of 3 cm
  • bendability
    • for example, bend tip and neck 90º without breaking
  • ability to maintain initial form
    • for example, restore to initial form following 45º bending

Manufacturers may describe the test performed, the number of samples and provide a summary of the results.

Strength and breakpoint (failure)

To limit the potential for patient harm, the minimum breakpoint distance should be about 8 cm to 9 cm from the nasopharynx. However, no breaks or fractures should occur following reasonable manipulation.

Applicants should submit a rationale for the design of the breakpoint distance from the swab tip. It should demonstrate that the breakpoint length can be accommodated by commercially available swab/media tubes.

Surface properties

The swab surface should be free of:

  • processing aids, such as disinfectants
  • foreign materials
  • degreasers
  • mold release agents

Injection molded swabs should not have any burrs, flashing or sharp edges.

Design validation

Provide swab validation (performance) data in a summary report that demonstrate the swab:

  • can acquire samples comparable to a commercially available swab control and
  • will not inhibit the PCR reaction

These data should be based on test samples representative of finished swabs that have undergone sterilization before testing.

Comparable sample acquisition to a control and PCR compatibility

The test swab cycle threshold (Ct) recovery values (RT-PCR) should be statistically comparable to those from a commercially available swab control using SARS-CoV-2 (or a scientifically justified surrogate).

Pass/fail criteria

Values ≥2Cts should indicate significantly less efficient ribonucleic acid collection and/or elution.

Clinical feasibility and suitability simulation

Manufacturers should submit either:

  • a clinical test report or
  • previous clinical data

Clinical test report

The clinical test report should describe the use of the proposed finished swab (sterilized) in a minimum of 30 patients who have tested positive for SARS-CoV-2 or a scientifically justified surrogate virus. The test should be conducted by trained health care professionals. It should compare the proposed swab against a flocked swab commercially available in Canada with respect to:

  • flexibility
  • fit
  • ability to navigate to the nasopharynx (or other areas specified in the indications)
  • ability to collect a specimen/respiratory epithelial cells
    • for example, using the RNase P housekeeping gene
  • test results agreement
    • for example, ≥90% positive % agreement using a composite control (positive % agreement calculation to include all positive findings from control and test swabs)

Clinical testing considerations

  • A scientifically justified surrogate virus may be used if COVID-positive patients are not available.
  • Positive % agreement should not be determined using high Ct samples. At least 1/2 to 2/3 of COVID-positive samples should have high viral loads (Cts <30).
  • There should be report agreement between control and test swabs in terms of quantitative (Ct) and qualitative (+/- test) values with appropriate descriptive statistics. Include patient symptomatology for samples.
    • for example, days from symptom onset, known vs. suspected COVID status
  • Ensure consistency by using the same media/tubes for each specimen within a clinical evaluation. Using different virus transport media/universal transport media (V/UTM) across COVID-positive samples may contribute to Ct variability.
  • Validate the chosen V/UTM media/tubes to show they will not interfere with the PCR test results.
    • for example, allowing 7 days of swab positive specimen incubation with the chosen media/vial is considered a worst-case transportation scenario to evaluate maximal leaching/interaction potential)
  • Use a single PCR test platform throughout each clinical evaluation. The platform should have been previously authorized by HC or another jurisdiction.
  • Location (for example, left vs. right nostril) and order of sampling (for example, control vs. test swab) can affect specimen quality and results variability. Location and swab sampling order should be randomized.

For more information on collecting, handling and testing COVID-19 specimens, please refer to the Centers for Disease Control and Prevention (CDC) Interim Guidelines for Collecting, Handling and Testing Clinical Specimens for COVID-19.

Previous clinical data

Previously obtained clinical data may be submitted instead of clinical testing. Those data should demonstrate the safe and effective use of a swab of identical design and materials in human subjects. The proposed swab should be compared against a flocked swab commercially available in Canada with respect to:

  • flexibility
  • fit
  • ability to navigate to the nasopharynx (or other areas specified in the indications)
  • ability to collect a specimen/respiratory epithelial cells
    • for example, using the RNase P housekeeping gene
  • test results agreement
    • for example, ≥90% positive % agreement) using a composite control (positive % agreement calculation to include all positive findings from control and test swabs)

Sterility

Provide sterilization validation data in a summary report. It should demonstrate that the chosen sterilization method will achieve a minimum sterility assurance level (SAL) of 10-6 for the proposed swab, using an appropriate biological indicator (BI) organism (see below).

If the swab is sterilized using an ethylene oxide (EtO) method, you should demonstrate that EtO and ethylene chlorohydrin (ECH) residuals meet the tolerable contact limits (TCL) specified in ISO 10993-7. Commonly used swab materials, compatible sterilization methods and appropriate biological indicators are described below.

Sterilization Method
Swab Materials EtO
(for example, ISO 11135)
Gamma Irradiation
(ISO 11137)
Polystyrene handle, polyester bicomponent fiber tip X
(for example, Puritan 25-3316-H/U)
Not applicable
Polystyrene handle, nylon flocked fiber tip X
(for example, Copan 503CS01)
X
(for example, BD 220252)
Footnote *
The CDC provides guidance on the types of swabs that should be used for optimal specimen collection for PCR testing. Swabs made of polyester (for example, Dacron), rayon or nylon-flocked are included. Cotton-tipped or calcium alginate swabs are not acceptable because residues in those materials inhibit the PCR reaction.

Appropriate BI

If ionizing radiation will be used to sterilize the swab:

  • Bacillus pumilus spores are recommended for doses of 25 kGy
  • Bacillus cereus or Bacillus sphaericus spores are recommended for doses of >25 kGy (World Health Organization, The International Pharmacopoeia, 9th Ed., 2019)
Sterilization Process Spore (Indicator Organism)
Steam Geobacillus stearothermophilus
(formerly Bacillus stearothermophilus)
Dry heat Bacillus atrophaeus (formerly Bacillus subtilis var. niger)
Ethlylene oxide Bacillus atrophaeus (formerly Bacillus subtilis var. niger)
Hydrogen peroxide Geobacillus stearothermophilus
(formerly Bacillus stearothermophilus)

Packaging validation

Provide packaging validation data in a summary report. It should demonstrate that the swab packaging system will maintain a sterile environment across the labelled shelf life (for example, ASTM F1980):

  • without leakage (for example, ASTM D3078-02)
  • with adequate seal strength (for example, ASTM F88/EN 868-5)

Test packaging samples should be representative of finished swab packages that have undergone sterilization before testing.

Biocompatibility

Provide biocompatibility data in a summary report. It should demonstrate compliance with biocompatibility tests recommended for devices in limited contact (≤24 hrs) with mucosal membranes (see ISO 10993-1). These include:

  • cytotoxicity
  • sensitization
  • irritation/intracutaneous reactivity

These data should be based on test samples representative of finished swabs that have undergone sterilization before testing.

Labelling

Swabs should be individually packaged and labelled. The application must include the swab label, which must include:

  • the name and model number of the device
  • the term ‘sterile,’ along with the sterilization method (EtO = ethylene oxide; R = gamma irradiation), if the swab is intended to be sold in a sterile condition
  • the name and address of the manufacturer
  • manufacturing and expiry dates

If swabs are not sterile but must be sterilized at the user facility, then the sterilization parameters and method should be clearly described in accompanying instructions for use documentation.

Post-market requirements

Within 10 days of becoming aware of an incident in Canada, all IO authorization holders must:

  • report the incident
  • specify the nature of the incident
  • specify the circumstances surrounding the incident

MDEL holders importing and/or selling swabs in Canada must follow the requirements set out under the MDR. This includes complaint handling, mandatory problem reporting and recall reporting.

While the IO does not have unique requirements related to recalls, any device authorized under thee IOis subject to the mandatory recall provisions under the Food and Drugs Act. Also, while the Minister has the ability to order a mandatory recall, manufacturers should proactively notify Health Canada if they become aware of the need to recall their COVID-19 medical device in Canada. The guide to the recall of medical devices provides guidance on how to conduct a recall in Canada.

Health Canada may engage in activities to assess compliance with the IO authorization and/or MDEL requirements and take immediate action when non-compliance is confirmed. This includes stopping the importation and sale of any products that are found to pose a risk to the health of Canadians.

Via https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/medical-devices/testing/test-swabs.html