India’s reliance on bedaquiline donations limits access to the key anti-TB drug

India is home to the most number of TB patients in the world. In 2017, 10 million new cases of TB were reported, of which 2.8 million patients resided in India. The country also has the highest number of patients with DR-TB, an advanced version of the airborne disease. The most powerful antibiotics do not work on such patients. When two of the most powerful antibiotics used to treat TB do not work on a patient, it is known as multi-drug resistant tuberculosis, or MDR-TB. If four main antibiotics do not work, it is known as extremely-drug resistant tuberculosis, or XDR-TB. By the Indian health ministry’s conservative estimates, India has 1,47,000 DR-TB patients.

In 2012, bedaquiline became the first drug approved by the United States Food and Drug administration to treat DR-TB. Making it available to Indian patients was critical to containing the global pandemic. Nadda’s announcement was keenly followed within the global public-health community, which had been waiting for India to start using the most effective medicine for DR-TB.

India is accessing this drug solely through the Bedaquiline Donation Program, a collaboration between the United States Agency for International Development and the American pharmaceutical giant Johnson & Johnson, or J&J, which currently holds the patent for the drug. In December 2014, J&J announced that its subsidiary, Janssen Pharmaceuticals, would donate $30 million worth of bedaquiline to low-and middle-income countries over a four-year-long period. Until March 2019, when the donation program was phased out, India had received 10,000 doses. In April 2019, the company donated an additional 10,000 doses to India.

Three years after the glitzy launch of bedaquiline, responses obtained under the Right to Information Act reveal that the Indian health ministry does not have a clearly defined framework guiding its procurement of the drug, nor a spelled-out donation policy. In response to multiple right-to-information queries I filed in June 2019, the health ministry said that it had not signed a memorandum of understanding with USAID and J&J, nor laid down terms of references while signing on to the donation program. The ministry’s RTI responses and publicly available documents, such as the health ministry’s guidelines on the use of bedaquiline, show that the only paperwork done to bring bedaquiline to India was an import license granted to Janssen in January 2015.

In one of its RTI responses, the health ministry said that “there is no MOU or agreement carried out for the drug courses provided under USAID Bedaquiline donation program.” In another RTI query asking for specific terms of agreements for the additional 10,000 doses of bedaquiline that J&J donated in April 2019, the health ministry once again replied that “there are no terms of agreements carried out between USAID and RNTCP for additional 10,000 Bedaquiline courses under USAID donation programme in 2019.” The Revised National Tuberculosis Control Programme, or RNTCP, is the government’s division to address the TB epidemic in India.

Health activists, lawyers, and TB survivors told me that they were concerned at the lack of transparency with which the Indian government has procured the drug, and the government’s reliance on a temporary donation program, where patients must depend on the generosity of a pharmaceutical company. So far, the Indian government has depended entirely on donations from this program to procure bedaquiline. Further, there is little clarity on how the donations are being used, and how doctors determine which patients qualify to access the drug.

Currently, India has access to only 20,000 doses, when at least 1,47,000 patients qualify for it under the World Health Organisation’s treatment guidelines, which recommend that DR-TB patients be treated with bedaquiline. While the Indian health ministry on paper, allows bedaquiline for all patients with drug resistance, media reports estimate that only 2.2 percent of eligible patients are currently receiving the drug. The medicine is being given out through select authorised government hospitals.

According to email responses from the health ministry’s TB division, a mere 4,227 bedaquiline doses were administered via government hospitals in the years 2018 and 2019. Patients have had to compete with each other to get access to bedaquiline because of the manner in which the health ministry has chosen to bring this new medicine to India. The scramble for this medicine was exemplified when a teenage girl from Patna, Bihar, successfully sued the health ministry to access bedaquiline. The teenager was diagnosed with XDR-TB, but had to wait five years and move court before she got access to it.

Within the global public-health community, it is widely accepted that drug donations are not sustainable for ensuring access to treatment for patients. Experts maintain that accepting donations undermines long-term efforts to incentivise pharmaceutical companies to develop products at affordable prices. “Drug donations are not a long-term solution to meeting the needs of patients; donations are time-limited stopgap fixes that come with restrictions on where, how and who can access the medicine,” Dr Jennifer Cohn, the medical director at Médecins Sans Frontières, an international humanitarian-aid agency, said. “The best way to get as many people on treatment as possible is for Janssen to simply offer the drug at a more affordable price for everyone in low and middle-income countries.”

Critics add that India has not followed the global best global practices in drug procurement, as recommended by the WHO. In 2010, WHO updated its guidelines stating that “there are many examples of medicine donations that have caused problems instead of bringing relief.” The report specifically pointed out that long-term donations are unsustainable. “As a general rule, medicine donations are neither a long‐term solution to underfunded health systems nor a solution to the lack of access to medicines in poor countries—especially for diseases that require lifelong treatment or large numbers of treatments. However, donations can be temporary solutions to defined problems,” it said.

Patient-survivors, such as Mumbai-based Nandita Venkatesan, who lost her hearing due to toxic injections used before bedaquiline was available, have been criticising the government on the lack of a clear sustainable policy. “The policy around procuring bedaquiline has been ad-hoc, opaque, and no one has any idea about what has transpired between the parties,” Venkatesan told me. “Key stakeholders, including patients, should be consulted when framing such a policy. The reality is that not all those who are eligible are receiving the drug, and those who are, are receiving it too late. We are depending on a single manufacturer for piecemeal donations. The WHO has clear and well laid-out guidelines for donations, which state that the donation may eliminate or greatly delay the import of cheaper alternatives, which will be necessary once the donation programme has ended.”

The USAID-Janssen donation program officially ended in March 2019. Any further procurements of bedaquiline are likely to be priced at $900 for a six-month course. Patients with DR-TB typically need a course of 18 months, which means a cost of about $2,700 or over Rs 1,90,000. The Indian health ministry is yet to clarify what the government’s strategy is to make this medicine available to the lakhs of patients in need. An estimated 2.79 million TB patients get infected with TB annually, according to the Indian health ministry’s latest National Anti-Tuberculosis Drug Resistance Survey. Email queries sent to the health secretary Preeti Sudan on 8 August remain unanswered. Janssen holds the patents for producing bedaquiline until 2023.

There are two other ways that the government can bring bedaquiline, or any other patented drug, to India—by issuing a compulsory license or a voluntary license. A compulsory license, or CL, can be issued when a government declares a national health emergency. In such a situation,

the government can allow another local company to manufacture a patented product, with the innovator company getting paid a royalty. This legal provision is one of the options available to signatories of the Trade-Related Aspects of Intellectual Property Rights Agreement, or TRIPS—an international legal agreement between all the member nations of the World Trade Organisation.

India has issued a CL only once. In March 2012, the controller of the Indian Patent Office ruled against the German pharmaceutical company Bayer Corporation. The license granted the Indian generic drug manufacturer Natco Pharma Limited the permission to manufacture and sell Bayer’s patented drug, Nexavar, in India. The drug is used to treat advanced stages of kidney and liver cancer.

Compulsory licenses are drastic measures, and governments usually resort to them after they have failed to negotiate a voluntary license. A VL is one where the patent owner voluntarily grants the permission to a generic drug maker to manufacture and sell the drug, upon mutually agreed terms and conditions. The drug-making company pays the patent-owning company fees and royalty on sales.

In response to one of my RTI queries, the health ministry confirmed that it had called a meeting between J&J, the innovator company, and Indian domestic drug manufacturers such as Hetero, Lupin, and McLeod’s, in the hope of negotiating a VL. In the RTI reply, the health ministry said, “A special meeting [was] carried out by CDSCO”—the Central Drugs Standard Control Organisation—“to discuss [the] feasibility to manufacturing Bedaquiline through voluntary license with leading Indian manufacturers. They (Lupin, McLeods, Hetero, and J&J) have stated that they have capacity and technology for manufacturing the drug.”

However, in response to my email queries sent in July, J&J confirmed that it had refused to sign a VL. “Rather than pursue voluntary licensing, J&J is working diligently with RNTCP on its national TB program to increase patient access to bedaquiline, in a manner that is responsible, affordable and sustainable,” a company spokesperson said.

“India is getting sweetheart donation deals because multinational corporations do not want competition from its generic manufacturers who have the capacity make and supply quality low cost versions of bedaquiline,” Leena Menghaney, the South Asia head for MSF’s Access Campaign, told me. Andrew Hill, a professor of molecular and clinical pharmacology at the University of Liverpool, has estimated that a generic version of bedaquiline could be sold at a price between $48 and $102 for a six-month course.

Patients and survivors have been questioning why India agreed to a donation model despite knowing that domestic drug manufacturers could produce the drug. “We don’t have a proper roadmap and framework for the way ahead on how to make this drug available to everyone who needs it,” Venkatesan said. “It’s appalling, to say the least, and shows a very casual approach to a critical problem.”

Experts on intellectual-property law have argued for a legal remedy. “Whether the donation is the correct way to go about procurement drugs is a debatable issue,” Anand Grover, a trustee of the Lawyers Collective, a legal non-profit, said. “Ideally, this is a situation for a compulsory license to be issued. The government can issue a license to generic manufacturer and the drug can be made at a fraction of the cost, right here in India. If that is not an option, a voluntary license should be negotiated. If J&J is not agreeable to VL, the government should resort to a compulsory license, because the epidemic is snowballing. This is also in consonance with Indian law, to prioritise public health. In the current case, neither is happening and we are relying on donations. But donations have to be regulated by clearly framed policy guidelines. That is absent here.”

There is a third way of procuring bedaquiline. The drug is available to nations via Stop TB Partnership’s Global Drug Facility, or GDF, which has negotiated a discounted price of $400 for a six-month treatment. Stop TB Partnership is a global consortium of non-governmental organisations, governments, and public health organisations. The GDF, a division within Stop TB Partnership, is dedicated to procuring TB drugs. The discounted price was the result of hard bargaining by South Africa, another country with a high TB population. South Africa accounts for more than sixty-six percent of global bedaquiline use. Instead of relying on donations, the government purchases the drug from GDF, making it available to patients in South Africa for free. If it wanted, India could also purchase bedaquiline from GDF at the discounted price.

As things stand, the Indian government has failed to convince J&J to sign a VL, and has so far not considered the option of issuing a compulsory license, despite having domestic drug manufacturers with the capacity to make this drug.

“The donation process has to be strictly regulated,” a health activist said on condition of anonymity. “We have just chosen the least transparent option. What were the terms? What happens after it is phased out?” The activist said that leaving this space unregulated gives a lot of bureaucratic discretion to officials on a crucial public health issue. “Even when the government procures a single needle, it follows a strict procurement guideline. What is the system being followed here?”

Source: The Caravan