For 10 months, private pathology labs and the SA Health Products Regulatory Authority (Sahpra) have been in a standoff about the use of antibody tests to detect if a person has been infected with Covid.
The regulator has not approved multiple laboratory tests for use in the country, despite being in negotiations with private pathology labs since last May — and three private labs producing their own studies of the tests’ effectiveness in June.
Clinical virologist Prof Eftyhia Vardas says SA’s private labs are, as a result, using substandard tests in some cases. And, she says, the process to verify the tests — which have already been approved for emergency use by the US Food & Drug Administration (FDA) and the European Medicines Agency — is unnecessary.
The antibody lab tests at the heart of the conflict were developed by various pharmaceutical manufacturers. These tests are not the polymerase chain reaction (PCR) tests used to diagnose Covid by looking for segments of the virus in a DNA sample. They are laboratory tests that look for Covid antibodies, which develop in response to infection with SARS-CoV-2.
Lancet virologist Dr Allison Glass tells the FM these tests are requested by doctors when a patient has serious symptoms of Covid but has produced a negative PCR test, as well as to determine how widespread the disease has been in a country, or in specific places like old-age homes.
Sahpra wants all the lab antibody tests to be retested to see if they measure what they say they do, but this has taken 10 months and is still not complete.
Making the standoff more unusual is that Sahpra has not previously required that laboratory tests be validated to ensure they are accurate before labs can buy them, says health lawyer Elsabé Klinck.
Evaluating whether tests work has always been left up to the labs themselves, and done in accordance with international guidelines. This remains the case for lab tests for diseases other than Covid, says Klinck.
In Vardas’s view, it is "an unprecedented and unnecessary process for Sahpra to insist on repeating this type of evaluation for Covid antigen and antibody tests. It would be similar to insisting on repeating phase 3 trials for a Covid vaccine in SA for each new Covid vaccine submitted to the regulator."
She says the lengthy process is "a waste of time and money", given the extent and severity of the epidemic.
The antibody tests in question are "high-throughput" tests, meaning they test multiple patient samples concurrently, and are compatible with existing pathology equipment and machinery used in SA’s labs.
It is an unprecedented and unnecessary process for Sahpra to insist on repeating this type of evaluation for Covid-19 antigen and antibody tests
— Eftyhia Vardas
One of the consequences of the lack of access to these tests became clear in January, when the SA National Blood Service (SANBS) conducted a study of blood donor samples to detect what percentage of the SA population had been infected with Covid.
Such prevalence studies are important, as they help scientists understand how widespread the epidemic is. (Not every infected person would have a PCR diagnostic test and be included in the official case count.)
As the high-speed antibody tests were not available in SA at the beginning of the year, the SANBS study was much smaller and isolated to just four provinces, where fewer samples were evaluated, the SANBS tells the FM.
SANBS operation manager Marion Vermeulen says the study only gave results for Covid prevalence in the Eastern Cape, KwaZulu-Natal, the Northern Cape and the Free State, because the lab tests needed to analyse large numbers of blood samples in other provinces were not available, and the ones available for use were inappropriate for the large number of samples.
"The lower-throughput instruments cannot handle the number of samples that we receive on a daily basis in the Joburg lab and the Western Cape lab," she says.
The lack of tests has also affected people travelling to China from SA.
Chinese authorities require travellers to submit not just a negative PCR test result, but also a negative test for a specific antibody, called immunoglobulin M (IgM).
None of the lab-based blood tests for IgM has been approved in SA. Lancet’s Glass says only IgM tests known as point-of-care tests — used by doctors and pharmacies, not labs — can currently be used for travellers to China.
"The results are far from ideal," she says.
The FM has seen a letter to Sahpra from three main local labs — Lancet, Ampath and PathCare — explaining the poor-quality results coming from the IgM tests currently in use.
When it comes to validating the Covid antibody tests, Sahpra has asked a Joburg National Health Laboratory Service (NHLS) lab to run the process, saying it wants one single laboratory to do this.
"The intention of using the national reference laboratory is to ensure a centralised, consistent validation protocol for performance," says Sahpra CEO Dr Boitumelo Semete-Makokotlela.
But because the NHLS lab in Joburg has not done this type of testing before, it did not have the necessary equipment. Sahpra confirms that the lab had to purchase equipment first. And the NHLS tells the FM it was short of blood samples in some instances.
Sahpra defends the NHLS lab doing the testing as a high-quality lab — an "accredited facility [run] by appropriately trained staff that complies with global best practice".
And the health regulator maintains that its course of action is correct: it is being stringent as a regulator and has avoided having to recall tests, as has happened to the FDA in the US.
Semete-Makokotlela said in a webinar last week that the regulator has been correct in taking its time to validate the tests, despite the pressure it has faced, "as they had very varied performance across the world".
"I am very proud to say unlike the FDA [that] has had to recall some test products, in SA we have not had to do that because of the stringency we have applied," she says.
However, the FM understands that the tests recalled by the FDA were point-of-care tests, not laboratory tests, so they are unrelated to the tests awaiting approval.
In any case, as Vardas explains, lab tests always need to be validated by every lab before they are used.
The labs have to check that tests really measure what they say they do — and this is done in accordance with international guidelines.
In Glass’s view, "the private labs are well placed to conduct the verification studies that Sahpra requires because we have existing quality systems in place that dictate this step before we offer any test [and] we have the diagnostic expertise and instrumentation".
In June, clinical pathologists at Lancet, Ampath and PathCare — part of a group of private pathologists called the National Pathology Group — conducted their own studies of the quality and accuracy of the antibody tests.
The labs then shared their study findings with the regulator, and offered to make three sets of raw data available and answer questions around their study methodology.
The labs also shared their results with the Foundation for Innovative New Diagnostics, a global nonprofit that works with the World Health Organisation in providing diagnostic tests for major diseases affecting the world’s poorest populations.
The refusal of the regulatory body to accept antibody tests by private pathology labs is causing frustration and delays
— What it means:
Sahpra does not tell the FM why it rejected the three labs’ validation studies, simply repeating that it wants a single lab — the Joburg NHLS one — to do all testing.
But the NHLS has confirmed that the lab doing the antibody test verification does not have enough samples for the testing. (Subsequent to the FM asking questions about the matter, the NHLS issued a press release asking for volunteers so it could generate 300 blood samples.)
The NHLS also denies it is "overwhelmed and has fallen behind with verifying and validating tests".
It says one of the problems it’s facing is a technical one: very few samples have the right IgM antibodies required for the studies. And it says it has repeatedly asked private labs to share their samples, but has yet to receive any.
In the meantime, tests manufacturers have been trying to register Covid antibody tests for more than 10 months, without success, says Klinck.
The slow verification process will continue to affect anyone travelling to China, and delay prevalence studies that could be useful in predicting the severity of the third wave. It also prevents health-care workers — the only group in SA to receive Covid vaccines so far — from assessing their responses and vaccine effectiveness.
Until the impasse is resolved and SA labs can access the tests they require, all antibody testing in SA vaccine trials will have to be sent overseas.
Ampath, PathCare and the Southern African Laboratory Diagnostic Association did not respond to requests for comment.
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