Analysis: Centre should make public the validation protocols for rapid test kits

A mere four days after supplying finger prick blood test kits for the novel coronavirus (Covid-19) to states, the Centre asked them to discontinue using these kits for fear they may not be of satisfactory quality.

Worldover, rapid antibody kits have come under the scanner over quality control issues. Even as the UK has now put its massive plan of rolling out these kits on the field on the backburner, India has distributed five lakh kits to states. These kits were bought at an estimated cost of nearly ₹26 crore from Chinese companies Guangzhou Wondfo Biotech and Zhuhai Livzon Diagnostics. The Spanish have returned their test kits and Germany is now trying to indigenously develop its own kits.

Up to five lakh kits arrived in India on April 16, and by April 17 these were distributed to the states. Chhattisgarh, for instance, received 4,000 kits made by Livzon, while Gujarat received 24,000 kits of Wondfo make.

R Gangakhedkar, Head, Infectious Diseases, ICMR, while distributing kits to the states had said that the Chinese companies ‘claim’ a certain specificity (84 per cent) and sensitivity (81 per cent) which will have to be checked as the kits are rolled out on the field. On April 21, however ICMR said states had reported a variation of between 6 per cent and 71 per cent in detection results which is a matter of concern.

While validating these kits, ICMR had earlier only apparently tested a stipulated number of samples kits, and had not conducted batch-wise quality control checks on kits that have been deployed on the field.

Of the 23 antibody kits ICMR had validated at its National Institute of Virology lab in Pune, on April 16, it put out a list of 14, which included kits made by Wondfo and Livzon. However, ICMR has not made public the methodology by which these kits were validated. In layman’s terms, the apex research body has not revealed how it came to the conclusion that these kits work accurately on the field.

In a disclaimer in the list, ICMR said, “(The) above listed kits are validated with the mentioned batch number only. Responsibility for batch to batch consistency lies with the manufacturer.”

But after various states started making noises about quality control, ICMR put the testing plans on hold, and sent its officials out on the field to conduct batch-wise quality checks.

Even as ICMR embarks on the arduous process of validating the kits batch-wise, it has not made public its earlier lab validation protocol that it employed to give a go-ahead for these kits in the first place. ICMR had also stated that any kit approved by the European regulator CE-IVD will also be considered reliable. Now that many kits are failing the scanner in Europe and the UK, health experts are demanding that protocols for validation of diagnostic kits be made public.

“Protocols for validation of diagnostic kits should be made public. Given the uncertain performance of the imported kits, ICMR must put in place guidelines for more thorough scrutiny and quality checks of imported test kits,” states Malini Aisola, co-convenor of All India Drug Action Network.

ICMR had earlier recommended rapid antibody tests for any person in a hotspot after seven days of their showing flu-like symptoms. A person who tests positive is quarantined for the next seven days and referred to a hospital if the symptoms appear or worsen. One who tests negative is still advised to be quarantined for a week. If a clinician deems fit, they can run the lab based RT-PCR tests on the suspect cases, too, the advisory stated. People are also needed to follow precautions of social distancing, wear masks, avoiding unnecessary travel and washing hands frequently.

Based on this protocol, Chattisgarh used 200 of the antibody kits in a hotspot, Kathgora, on April 20, and found that a 24-year-old suspect male (because of his travel history) was the only one who tested positive of the pool. “Earlier RT-PCR tests on his throat and nasal swab had been negative. This means that the patient could have been positive earlier, but RT-PCR tests were run late on him, in the beginning of April. He may have shed the virus, but developed antibodies for which he tested positive. The patient is in quarantine and doing well. The accuracy levels of these kits have now emerged as a concern, even as they helped us in best guess scenarios like these,” said a senior official from the State Health Department. Rajasthan, on the other hand, after testing 168 patients who had already been RT-PCR positive to compare the tests, stated that most kits that they used were not throwing up results and it was discontinuing testing.

The chances of false positives or false negatives in these kits are very high, Government Advisor on Life Sciences for the UK government Sir John Bell has warned in his commentary , published by the University of Oxford. A false positive means the test shows the person undergoing the test had the virus, when actually he/she didn’t. And a false negative would mean the person being tested had the virus, but the kit shows otherwise. Hence, the person would be falsely reassured he/she was fine despite being infected. This means self-testing is not advisable.

Bell states: “There are many challenges to creating accurate tests; hence these tests need to be validated carefully. Other countries such as Spain have already sent tests back because they don’t work. There are 100 or more such tests kits from different suppliers available for identifying Covid-19 antibodies, and it is important that each of these is checked for accuracy before making them available to the public.”

Bell explains the tools required to validate the kits. He says, “To validate these tests you need to obtain a range of tools. You need a gold standard test so you know the correct answer and you need sera from patients who have recovered from the virus infection they had approximately 28 days before. You also need blood from people who donated before the epidemic so you know whether you falsely see positive tests when there is no Covid-19 in the sample. For example, there are a number of other coronaviruses circulating that might stimulate antibodies that cross react to Covid-19 proteins.”

As the Centre now puts all testing plans on hold to revalidate the kits, it is also pushing Indian companies to develop indigenous kits. But any such production will take at least a month or more from now, industry experts have indicated. Until such time, for transparency sake, ICMR could do well to put its quality control protocols in the public domain.

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