Key to fighting the coronavirus pandemic is a country’s ability to create strong supply chains of crucial materials like testing kits and safety gear. This report is part of series that takes a closer look at how India has fared on this front so far.

On Thursday, April 16, officials at the Indian government’s daily press briefing had good news to share: the first consignment of 5 lakh rapid antibody testing kits had finally arrived from China.

The order had been placed by the Indian Council of Medical Research on March 30 and was expected to arrive on April 5. But it had been caught in a string of delays, as China tightened its export policy after widespread complaints about malfunctioning Chinese testing kits in Europe.

While the consignment’s arrival was greeted with relief across the country, a sobering fact remained: 5 lakh kits amounted to just 10% of the total number of antibody kits ordered by the ICMR. In addition to the orders placed by the ICMR, an organisation that works under the Central government, many state governments had separately ordered lakhs of kits from China and Europe. Not only have these orders not materialised so far, the prospects of delivery look weak in the face of global shortages.

Naturally, India would do well by ramping up indigenous production of these kits, which can help map the spread of the novel coronavirus within the country, helping the authorities discern patterns of the disease and formulate better strategies to combat it.

Nine Indian companies, in fact, have assembled kits which have been tested and approved by the National Institute of Virology in Pune, the sole government lab in India which is evaluating these kits.

But domestic production has been delayed, among other reasons, because of regulatory complexity.

Take the example of HLL Life Care, a central government-owned company. The NIV cleared HLL’s rapid testing kits on April 4, said an official of the company who did not want to be identified. But the company could not start production right away – it had to apply for a manufacturing licence from the Drug Controller General of India who heads the Central Drug Standards and Control Organisation, which gives licenses for import and manufacture of all drugs and diagnostics in India.

“We applied to DCGI the very next day,” said the HLL official. But the licence came only a week later, on April 13.

Other companies have also complained about being held up by the DCGI despite being given a go-ahead by NIV, Pune. The Drug Controller General of India VG Somani did not respond to queries about these alleged delays.

The regulatory hurdles are only exacerbating an already slow process that scientists say is crucial to unravelling the mysteries of India’s coronavirus outbreak.

The importance of antibody tests

To identify active cases of the novel coronavirus disease or Covid-19, India collects nasal or throat swabs of suspected patients and puts them through the RT-PCR or reverse transcriptase polymerase chain reaction test. This test looks for the presence of the virus in the DNA of the patient. A complex test, it takes between 12-24 hours to yield results.

In comparison, the antibody tests, also known as serological tests, are easier to administer: blood samples, drawn from patients often using just a fingerprick, are scanned for disease-fighting antibodies. Results are available within 45 minutes to two hours. This is why antibody tests are also called rapid tests.

But the antibody test is less reliable than an RT-PCR test. Since antibodies show up only after 7-10 days of being infected by the virus, the blood test could throw up a false negative – an infected person may appear normal. One advantage, however, is that unlike the RT-PCR test which can detect the virus only within a limited window of a few days, the antibody test can detect older cases of infection since the antibodies remain in the bloodstream for months. This can help map the spread of the disease even among asymptomatic cases.

While placing the first order for antibody testing kits, the ICMR scientists told that these would be used precisely for such a study – to map the spread of the disease within India.

Blood samples are prepared for coronavirus testing at a lab in Germany, March 26, 2020. Photo: Reuters

But days later, Kerala and Karnataka announced they would use antibody tests for large-scale screening of patients with mild symptoms of the disease who did not have travel and contact history. Such patients were outside the purview of the RT-PCR testing regime at that time, which was limited to patients with travel and contact history, or those who were hospitalised with severe acute respiratory infections – or severe symptoms of Covid-19.

Close on the heels of the announcements by the states, the ICMR issued an advisory on April 4, which recommended antibody tests on people with mild symptoms of Covid-19 – called influenza-like illnesses – in hotspot areas or clusters reporting a high number of cases.

On April 9, the ICMR further refined its advisory. It expanded the RT-PCR testing regime to include residents of hotspot areas with influenza-like-illnesses or mild symptoms of Covid-19 – fever, cough, sore throat and runny nose. But such patients needed to be put through RT-PCR tests within a week of the manifestation of the illness. Once this window had passed, antibody tests were recommended, presumably because the virus would no longer be detectable in their DNA, only in their bloodstream.

“Gold standard frontline test for COVID-19 diagnosis” is the RT-PCR test, ICMR chief Balram Bhargava wrote to all state health departments on April 17. The antibody test is “a supplementary tool” to assess the prevalence of the disease, he said.

With the number of coronavirus hotspots in India rising to 170 as of April 17, it is clear that antibody tests are crucial to identifying infected people who would otherwise go under the radar.

State orders

The first Indian state to place orders for the antibody kits was Karnataka. It placed orders for 1 lakh kits on March 29 itself, even before the ICMR did.

Many other states followed up in the first week of April. Rajasthan ordered 1.25 lakh kits from a Chinese manufacturer, said Pritam B Yashvant, managing director of the state’s Medical Services Corporation Limited.

Kerala placed orders for 2 lakh kits from two separate manufacturers, according to Navjot Khosa, managing director of Kerala Medical Services Corporation.

On April 6, Jharkhand ordered 1 lakh kits, said Shailesh Kumar Chaurasia, who heads the state’s national health mission.

But like the ICMR, states have also been kept waiting by the companies they placed orders with. Several delivery deadlines have been missed, said officials.

Karnataka’s kits were yet to arrive till late evening of April 17 despite the state being one of the first to order, said CN Manjunath, a member of the state’s Covid-19 task force.

Among the states that received the kits is Rajasthan – a tranche of 10,000 kits, or 10% of its order, landed in Delhi on April 16 evening and were dispatched to Jaipur by road.

Gujarat received 24,000 testing kits on April 17.

Problems in China

The reason for the delays in kit deliveries is a logjam in China.

Most Indian importers have tie-ups with Chinese manufacturers, who are now having to get an added clearance from their government before they can export kits.

On March 31, Chinese government said that kit exporters would need the registration certificate from the country’s drug watchdog National Medical Product National Medical Products Administration to be cleared by China’s customs. This requirement came in the wake of widespread complaints about Chinese testing kits in Europe where countries have alleged that the accuracy of the kits was much less than promised.

India’s regulatory regime

But the problems extend beyond regulatory problems in China.

India has a dual system for clearances for antibody testing kits, which is creating much confusion.

Indian importers and manufacturers must get every batch of kits individually tested for efficacy at the National Institute of Virology in Pune, unless they have the Conformitè Europëenne certification, the European Union’s quality benchmark also known as European CE. The ICMR has waived off the requirement of NIV validation for kits with European CE.

But technical approval from NIV or European CE certification is not enough. Companies also need a marketing licence by the Drug Controller General of India to sell the kits commercially in India.

This has led to a situation where some companies have technical approvals but are still waiting for marketing licences from DCGI.

As of April 16, the NIV had validated 23 batches of rapid kits submitted for evaluation by 14 companies. Some companies had submitted more than one batch. Nine of the 14 companies were Indian. But five of them were yet to be given marketing licenses by the Drug Controller General of India.

Till April 16, the DCGI had issued marketing licenses to 49 companies for 66 rapid testing kits. Some companies had applied for licences for more than one kit.

Among these 49 Indian companies, only four produce their own kits. Minus these four indigenous kits, the remaining 62 licensed kits will have to be imported. As many as 47 of these kits are Chinese. All of them are European CE certification.

On April 3, the Chinese National Medical Products Administration released a list of eight companies with rapid kits that it had approved for export. Indian companies with DCGI licenses have tie-ups with only four of these eight Chinese companies. Between the four companies, they have a product portfolio of 21 kits.

This means only 21 of the 47 Chinese kits approved by the DGCI can be currently imported.

On April 16, the DCGA released a list of 66 approved antibody kits. This is the first page of the document.

Import-Export mismatch

As a result, some Indian importers have marketing licences to sell in India, but their Chinese collaborators do not have approval to export.

Take for instance, the Delhi-based company, Sowar Private Limited. The company has a collaboration with a Chinese company called Getein Biotech Inc based in Nanjing. Getein is yet to get a clearance from China’s National Medical Products Administration.

“We are in touch with our principal company every day – but they are still to get clearance from their government,” said Vijender Jaiswal, the person in charge of the import of the kits at the company. “Till then, we cannot import the materials.”

But it is not just Chinese companies which are struggling to honour their collaborations with their Indian counterparts. The Chennai-based CPC Diagnostics Limited has DCGI approval to sell kits manufactured by its German collaborator company, Euroimmune AG. However, even Euroimmune AG has not been able to export any kits.

“Euroimmune is unable to supply us because the demand is so huge,” said R Kailasnath, managing director, CPC Diagnostics. “They sent us a mail saying they were not even being able to meet the demand in their own country. The moment they feel confident about meeting demands, they will let us know.”

Indigenous kits

Given the intensifying global shortages, many are now asking if India missed the bus in imports because of ICMR’s late decision to clear the decks for antibody testing. It was only on April 4 that the ICMR issued an advisory regarding their use, following which most states started placing orders.

Malini Aisola, co-convener of the All India Drug Action Network, a watchdog organisation, said the fact that ICMR took too long to decide on the modalities of rapid testing was beyond doubt. “Testing protocol could have been cleared earlier. It came out very late,” said Aisola. contacted the ICMR for a response to this criticism but no response has been received so far.

The lack of availability of foreign kits means India’s rapid testing kit supply has to be now largely fulfilled by indigenous manufacturers. As of April 16, there are four of them who have technical as well as marketing clearances: the central government-owned HLL Lifecare, Vanguard Diagnostics, Voxtur Bio Ltd and SD Bio Sensor Healthcare Pvt Ltd.

But how ready are they and how much can they really pool in?

An official at HLL said the company was “in the process of manufacturing”. “We should be able to supply ICMR by next week,” he said. “We can supply a maximum of 20 lakh kits over a period of one month.”

The official said the company had received “instructions” to sell only to ICMR for the time being. Which means if it does indeed manage to start supplies to ICMR next week, there will be a considerable delay by the time states actually have possession of these kits.

Voxtur Bio Ltd was given a licence by DCGI on April 13. The NIV validated a batch of its kits on April 16. The managing director of the company, Khushroo Pastakia, said it was currently “procuring raw materials”, some of which had to be imported from outside the country. “That whole cycle takes around 10-12 days,” he said. After 12-15 days, the company would be able to produce 1 crore kits a month, claimed Pastakia.

Vanguard, the third company which has technical approval as well as a marketing licence, said it could start production in a couple of weeks. It refused to divulge details about its manufacturing capabilities. SD Bio Sensor Healthcare, which got both approvals on April 16, could not be reached for comment.

Peculiar problems

Meanwhile, Indian importers are making sure they do not run into unexpected problems. Even though ICMR has waived off the requirement for NIV validation for kits that have European CE certification, several companies with CE approvals seem to be voluntarily getting validated by NIV.

“We will do it because it is easier to sell products that have the government’s stamp on it,” said Vijender Jaiswal of the Delhi-based company, Sowar Private Limited, which has a collaboration with Getein Biotech Inc whose kits are CE approved. “It is no bother to send a couple of hundred kits to NIV since we are already going to import lakhs of them,” said Jaiswal. “And we will get an additional certification in three-four days.”

The managing director of another importer company said the NIV accreditation was important to do business in India. “The guidelines say that it is not necessary, but practically it does not work like that,” said the managing director, who did not want to be identified.