Every minute matters when an individual needs to know whether he or she has contracted COVID-19. Beyond social distancing and masks, COVID-19 testing solutions have an important role in preventing virus spread. By offering some certainty about the presence or absence of infection, diagnostic testing helps public health efforts to control the virus.
But at what levels will tests be needed? How can the medical device industry scale up test manufacturing capacity and ensure a stable supply to the U.S. market?
With their rapid diagnostic capabilities, lateral flow immunoassay (LFI) antigen tests are among the technologies that healthcare providers and public health organizations are adding to their testing inventories. Following is a discussion of these LFI diagnostic devices and the manufacturing operations needed to produce them in large volumes. But first, a look at the broader picture.
COVID-19 Testing Overview
As of July 2020, the COVID-19 diagnostic testing capacity in the United States was estimated at between 520,000 and 823,000 tests daily. One U.S. government initiative aims to expand testing capacity so that by December 2020, approximately 2 percent of the U.S. population, or 6 million individuals, can be tested daily.1 How will the country close this gap?
Multiple COVID-19 test types will contribute to the increased capacity. As of this writing, the U.S. Food and Drug Administration (FDA) had issued Emergency Use Authorizations (EUA) for well over 100 molecular tests, two antigen tests, and almost 40 antibody tests. Below is a brief explanation of the test types.
Diagnostic Tests. Within this test category, there are two primary types of tests, including:
Molecular tests. The most common molecular test is the reverse transcription-polymerase chain reaction (RT-PCR) test, which detects the COVID-19 virus’ genetic material. The sample is a nasal or throat swab. This test requires processing in a specialized laboratory, and it usually takes a few hours to one week to obtain results, although some testing locations can offer same-day turnaround. 2
Antigen tests. This type of test is designed to recognize proteins on the surface of the virus.2 The sample is a nasal or throat swab. Antigen tests can be administered and read close to the point of care (POC), which is why they are also called rapid diagnostic tests. Results are available within 15–30 minutes.
Antibody Tests. Also known as serology tests, these tests identify antibodies that the body’s immune system has generated in response to COVID-19 infection. A sample of the patient’s blood is typically taken through a finger stick or blood draw. Results can be provided same-day or within one to three days. These tests show whether a person has been infected in the past but cannot diagnose an active COVID-19 infection. It takes the body several days to weeks to build up antibodies. 2
Paths to Scale Production
Regardless of the test type, many of the same scalability considerations will apply as the U.S. medical device industry expands its domestic manufacturing infrastructure. There are several paths to secure the needed additional production capacity. A device original equipment manufacturer (OEM) might choose to expand its operations or build a new manufacturing facility. Some may expand through acquisition. Others will look to partner with contract manufacturing organizations (CMOs) to accelerate test production, especially for the U.S. market.
By working with contract manufacturing partners, OEMs can avoid time-intensive and costly expenditures required to build their own manufacturing operations. Starting up a greenfield diagnostic test manufacturing facility would take at least one year, especially when hiring and training are factored into the timetable. By comparison, a CMO with market experience often can get a new product into production within a matter of months. Even if a CMO needs to bring a new production line up, this can usually be accomplished in six to nine months or sooner if the necessary equipment is readily available.
Inside a COVID-19 Antigen Test Kit
While there can be different configurations, a COVID-19 antigen test kit typically includes these items and functions as follows:
The LFI test strip, usually housed in a plastic cartridge (see Figure 1).
Sample collection swab.
A tube filled with an extraction reagent fluid.
A dropper (if one is not integrated into test tube).
The healthcare provider inserts the sample into the tube to mix it with the reagent solution. Then fluid from the tube is dispensed via a dropper into a designated well on the test device. The fluid then flows across the device’s sample pad, which has been treated with conjugate and reagent chemistries. This prompts a chemical response to the test specimen. The test is then inserted into a small, portable test-reading device to obtain the results.
The following step-by-step overview of the LFI test manufacturing process is an example of the process flow when a CMO engages with an OEM or other device developer to take a COVID-19 test to commercial-scale production volumes.
Pre-Process Activities and Process Development. First, the CMO and OEM embark on their technology transfer process.3 The CMO will perform supplier assessments, confirming that the right materials are available in the right format to run optimally on high-speed automated manufacturing lines. The CMO will develop standard operating procedures for how to mass produce the test. Materials will be procured and inspected, and manufacturing process trials and testing will begin.
Biochemistry Lab. In an on-site laboratory, the CMO takes the device developer’s proprietary test recipe — the conjugate and reagent chemistries — and prepares them in the quantities needed for large manufacturing batches. The reagent is one of the substances on the test strip that causes a chemical reaction when it comes in contact with the test specimen. In some LFI tests, the specimen might be blood or urine. For COVID-19 tests, the specimen is usually extracted from nose or throat mucous.
Reagent Deposition. At this stage, the reagent is striped, or coated, onto the test strip materials. The deposition may involve precision spraying or dip coating of blocking agents, conjugates and other sample pad treatments. Automated reel-to-reel (R2R) equipment enables efficient processing, in-line inspection, and reject marking. Reagent deposition is performed in an environment with controlled temperature and humidity.
Lamination. Next, the treated materials must be laminated together and slit into individual test strips. Here again, R2R automation allows for computerized vision inspection at high speeds while the materials are laminated and slit. This step must be performed in a low-humidity environment.
Assembly and Packaging. Finally, the test strips are placed into cassettes, or housings. For optimal manufacturing speed, efficiency, and consistency, this step ideally should be performed on robotic lines with automated reject management. The manufacturing configuration can include automatic pouching so that tests are ready for shipment as they come off the assembly line.
Process Verification and Validation. Throughout COVID-19 antigen test production, it’s crucial to verify quality, performance, and consistency at regular intervals. As it scales up manufacturing, the CMO will validate that the test is still performing properly lot-to-lot, device-to-device. This ensures diagnostic accuracy and reliability, regardless of whether it’s the five-thousandth test to be produced or the five-millionth.
Testing is crucial in the fight to control COVID-19 and keep people safe as this pandemic runs its course. With the right supply chain alliances and automation, COVID-19 antigen tests can be manufactured in the large quantities required by the United States. LFI antigen tests provide results rapidly, at or near the point-of-care. These test results help individuals, businesses, and governments make important decisions that affect not only personal health and employment but also the well-being of entire communities, companies, and the national economy.
- Tromberg BJ, Schwetz TA, Pérez-Stable EJ et al., “Rapid Scaling Up of Covid-19 Diagnostic Testing in the United States — The NIH RADx Initiative,” N Engl J Med, Special Report, July 2020. Accessed July 28 , 2020.
- Coronavirus Testing Basics. FDA. Updated July 16, 2020. Accessed August 12, 2020.
- C. Hanna , M. Conary , “Demystifying Technology Transfer in Medical Device Contact Manufacturing,” Medical Design Briefs, Vol. 9, No. 3, March 2019.