India is staring at an extreme shortage of Tocilizumab, a medicine administered to COVID-19 patients in the ICU, across the country. In the last week, shortages of the drug have already been reported from Chandigarh, Chhattisgarh, Maharashtra, Kerala and Delhi.

Cipla, the only company which markets it, has said it does not know when stocks would be available.

Tocilizumab is one of the patented drugs for which the government should issue a compulsory licensing clause, but it hasn’t so far.

Known as a ‘rich man’s drug’, Tocilizumab, which costs between Rs 40,000 – Rs 50,000 for a single dose in India, is manufactured by Switzerland-based pharmaceutical company Roche and is marketed by Cipla in India.

An immune-suppressing drug, Tocilizumab, commonly used for rheumatoid arthritis, has been repurposed to fight severe lung infection in COVID-19 patients as it calms the inflammatory storm in the respiratory system by blocking IL-6 receptors.

“We currently do not have any stock remaining at Cipla. I am not sure exactly when the stock will arrive. There is a shortage of the drug currently,” said a senior management person at Cipla. He did not want to be identified.

Despite being on the clinical protocol, there is a shortage of the drug especially in Chandigarh, Maharashtra, Delhi, Chhattisgarh and Kerala. Chandigarh doctors have been complaining about the shortage for more than two weeks, and health workers in Maharashtra, especially in Pune, Mumbai and Nagpur, have already raised an alarm about its unavailability.

A BMC (Brihanmumbai Municipal Corporation) official said they had only a limited supply of Tocilizumab and that the corporation was finding it difficult to get the drug.

In Kerala, doctors in medical hospitals across the state have been attempting to obtain the drug from rheumatology doctors.

India’s clinical management protocol released by the Ministry of Health and Family Welfare has recommended Tocilizumab for managing severe COVID-19 cases. The protocol states that Tocilizumab Anti IL-6 therapy can be considered in patients with moderate disease with progressively increasing oxygen requirements and in mechanically ventilated patients who are not improving despite use of steroids, even though long-term safety data in COVID-19 remains largely unknown.

“Since Tocilizumab’s approval a decade ago, it has become the go-to drug against inflammatory conditions, including cytokine storms. A small cohort study in China has suggested that Tocilizumab effectively improved clinical symptoms and repressed the deterioration of severe COVID-19 patients,” wrote patent lawyer Chetali Rao and Third World Network’s legal advisor KM Gopakumar for a health policy watch website.

The guidelines warn that patients should be carefully monitored post Tocilizumab for secondary infections and neutropenia (low level of a certain kind of white blood cells which help the body fight infections). Tocilizumab cannot be used in patients with bacterial or fungal infections, tuberculosis, active hepatitis and low platelet count.

All India Institute of Medical Sciences has also recommended Tocilizumab to be used on case-to-case basis within 24 hours of a COVID-19 patient’s progression to severe as a part of the anti-inflammatory or immune-modulatory therapy.

Even Lok Nayak Hospital under the Delhi government had recommended Tocilizumab for moderate to severe cases especially in cases where oxygen levels were not improving.

A study published in The Lancet Respiratory Medicine said that Tocilizumab had increased survival among patients suffering from extreme COVID-19. The study conducted at 11 public and private tertiary-care hospitals in India revealed that a sub-group analysis of severe patients in the trial showed a lower mortality (8/50; 16%) among those who received Tocilizumab compared with those who did not (14/41; 34%) in 28 days.

A total of 180 patients were recruited at the centres, 90 of whom received Tocilizumab (TCZ) and standard care, whereas the other 90 received only standard care.

Compulsory Licensing Clause

“We do not how the percentage of people who are given Tocilizumab because it is an expensive drug. Even the World Health Organisation has stated that Tocilizumab is useful for COVID-19. Tocilizumab is a patented bio-therapeutic drug and in India it is marketed only by Cipla. They are importing it,” said KM Gopakumar, legal advisor for Third World Network (TWN), an international research and advocacy organisation.

Bio-therapeutic medicines are those which are made from living cells of organisms to make or modify protein products to create therapies. They have the ability to target specific molecules within the human body.

Pharmaceutical companies cannot produce the generic version of the drug in India because of two issues: firstly, there is a patent and secondly the regulatory system states that anybody who wants to produce this medicine has to carry out a comparative clinical trial and only then can it be marketed.

“The former can be overcome by a compulsory license. As Tocilizumab is a bio-therapeutic drug, comparative clinical trials are required, but this trial is actually not required. It is simply an entry barrier. A trial would take at least two years and we need the medicine now. Global scientists have written that this trial is not required. WHO had revised the guidelines in December 2020,” added Gopakumar.

The World Health Organisation’s Expert Committee on Biological Standardisation said in December 2020 that in the view of the ongoing pandemic, bio-therapeutics which require clinical trials can be waived off. Safety can be proven through in lab testing (in vitro) instead of human testing.

Compulsory licensing is when a government allows someone else to produce a patented product or process without the consent of the patent owner or plans to use the patent-protected invention itself. Section 84 of the Patent Act states that any person, regardless of whether he is the holder of the license of that patent, can make a request to the Controller for grant of compulsory license if the patented invention is not available to the public at a reasonably affordable price.

There needs to be speedy action, Gopakumar emphasised, first from the patent office to give permission to develop this drug and second, regulatory approvals are required.

“It would take around four months for this medicine to be produced. It must be manufactured in India and the government should have thought of this. If we don’t do it at least now, are we going to suffer when there is a third COVID-19 wave? We don’t know how long this wave will continue either. As long as this virus is around, people will require the drug at an affordable price. Currently, it is extremely expensive,” underscored Gopakumar.