Indian generics, hydroxychloroquine and production capacity in global emergency

Indian generics, hydroxychloroquine and production capacity in global emergency

Indian generics are currently playing an important role in the global supply of hydroxychloroquine (HCQ), an old antimalarial drug that has been highlighted as a potential preventive treatment for COVID-19. In early April, the Indian External Affairs Ministry agreed to provide HCQ, after meeting domestic need, to neighbouring countries.[1] The clinical evidence on the drug’s effectiveness is mixed, with Chinese and French trials reporting mixed success with the drug, and a recent controversial retrospective study (neither peer-reviewed nor published) reported that the drug had no effect on COVID-19.[2] However, according to health interest groups, studies invalidating HCQ had some issues and the drug, when used in combination with Vitamin D, zinc and other supplements according to each patient’s case and underlying conditions, can be effective. At the very least, a sensible public health strategy would try to have HCQ on hand, along with other therapies.[3]

There are several angles of analysis for a global health historian, such as an emerging Indian humanitarian foreign diplomacy through generics. This was a key theme in companies such as Cipla, an Indian generic pharmaceutical company, making antiretroviral treatments available globally in the early 2000s.[4] Another theme I will focus on here is the issue of production capacity during a global emergency, because the Indian generic hydroxychloroquine situation of early April 2020 mirrors the case of Burroughs Wellcome’s azidothymidine (AZT, or trade name Retrovir) during the global AIDS crisis [keeping in mind that antimalarial HCQ is different from AZT, which is based on cancer and antiviral research].

The key issue in making Burroughs Wellcome’s Retrovir available globally in the late 1980s to early 1990s outside of the biggest markets of US, Europe and Japan was production capacity, which ramped up cost. Though the company had no significant competitors and essentially held the market, it was not able to manufacture azidothymidine at scale and thus, costs were high. This was because thymidine, a key chemical compound, was originally sourced naturally as a by-product of salmon and herring sperm with low yield, so that much of what the company was trying to resolve throughout 1985 and 1986 was a). finding reliable and quality synthetic thymidine and b). upping processing capacity in the Greenville, US and Dartford, UK manufacturing plants. This was also in reflection of the significant consumer activism occurring in its biggest market, the United States.[5]

However, when it came to supplying the drug outside of developed countries with earlier AIDS experiences, the dialogues between Burroughs Wellcome and the World Health Organization (the lead international health agency coordinating the global AIDS response) did not go anywhere. According to a former WHO AIDS official, Burroughs Wellcome had made several moves over the years indicating that it was willing to provide any extra stock in the form of donations, particularly in African countries with greater HIV prevalence than the rest of the developing world. Since treatments needed to be taken regularly, WHO concluded taking donations on behalf of the poorest countries would make the situation worse.[6] Instead, WHO received direct offers to synthesize AZT from secondary chemical materials companies in Asia that themselves had supplied raw materials to Wellcome Burroughs for Retrovir. Due to intellectual property and legal issues (WHO traditionally does not overstep pharmaceutical companies, but this is another matter for another post), as well as the problems with consistent quality, WHO shut down this approach, until Indian generics acted in the early 2000s. In hindsight, it is puzzling why Burroughs Wellcome did not use its time holding the market to explore expansion overseas, as commercial strategy not to mention the ethical implications.

Today, Indian generic companies seem to have responded with calm, speed and consistency to global need, just as they had done during the HIV/AIDS pandemic. After an initial hold to determine domestic need, India exported hydroxychloroquine and paracetamol to neighbouring countries on humanitarian (donation) or via government contracts, and then the rest of the world.[7] However, there are some signs that even India may have some trouble meeting this vast demand, as according to a piece in Reuters that interviewed the Deputy Foreign Minister of Malaysia, stock requests may not be able to be fully met because the country was also donating the drug to less developed countries in Africa.[8] Though Indian pharmaceutical industrial federations have promised that production would be ramped up, they are themselves dependent on active pharmaceutical ingredients, especially chloroquine phosphate, from Chinese chemical companies to supply the raw materials.[9]

The situation has yet to be resolved and there are many layers of analytic approach. I do not think it can be easily explained with a moralising argument about generic vs. patented pharma. As a contemporary historian drawing from records of international organisations and pharmaceutical companies, I have read countless grey literature documents, indicating that the situation is much more complicated. However, I will argue here that the case of Indian generics and hydroxychloroquine shows how important a factor production capacity is in global disease emergency, just as much as intellectual property protection and research and development. We need much further research into the supply chains of chemical companies that provide chemical materials to pharmaceutical companies, generic and patented, and a richer understanding of the history of the current global infrastructure of drug manufacturing and chains of commercial availability that allow safe medicines in plentiful amounts being able to reach patients in need across the world.

[1] ‘Donald Trump’s Hydroxychloroquine Retaliation Statement and India’s Response’, India Today: YouTube (7 April 2020). <https://www.youtube.com/watch?v=wiA0fTG6H6A>. [2] Joseph Magagnoli, Siddharth Narendran, Felipe Pereira, et. al., ‘Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19’, 23 April 2020 <https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v2> [3] Dr Eric Berg DC (YouTube Channel), ‘A new study – hydroxychloroquine resulted in more deaths…but was it credible?’, 26 April 2020. <https://www.youtube.com/watch?v=SZEONtCP30g> [4] Katherine Eban, ‘How an Indian tycoon fought Big Pharma to sell AIDS drugs for $1 a day’, Quartz India (15 July 2019) <https://qz.com/india/1666032/how-indian-pharma-giant-cipla-made-aids-drugs-affordable/>. [5] Steven Epstein, Impure Science: AIDS, Activism, and the Politics of Knowledge (University of California Press, 1996). [6] Merson and Inrig, The AIDS Pandemic, 204. [7] ‘India to export hydroxychloroquine only to foreign governments and not to private companies: Sources’, Economic Times India (10 April 2020). <https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/india-to-export-hydroxychloroquine-only-to-foreign-governments-and-not-to-private-companies-sources/articleshow/75078549.cms?from=mdr>. [8] Neha Arora and Krishna N. Das, ‘Exclusive: India agrees to sell hydroxychloroquine to Malaysia to help fight COVID-19’, Reuters (15 April 2020). <https://www.reuters.com/article/us-health-coronavirus-india-malaysia-exc/exclusive-india-agrees-to-sell-hydroxychloroquine-to-malaysia-to-help-fight-covid-19-idUSKCN21X0YQ>. [9] Eric Palmer, ‘Chinese APIs flowing but India ban hinders U.S. approval of hydroxychloroquine’, Fierce Pharma (31 March 2020). <https://www.fiercepharma.com/manufacturing/chinese-apis-flowing-but-indian-ban-hinders-u-s-approval-hydroxychloroquine>.