First, how did this situation - that India could manufacture drugs at prices far below those in the global north - come to be? India's first Prime Minister Jawaharlal Nehru’s commitment to a scientifically planned nation-state brought forth a pharmaceutical industry that had been dormant during colonialism. One of the chief outcomes of Nehruvian science policies was in the arena of intellectual patents. During colonialism, the captive Indian market had been dominated by Euro-American firms, with little indigenous manufacturing capability. The inventions and patent landscape in the country too was dominated by Europe and the United States. Further, the products issuing from such patents were not marketed in India. They served only to block competition from Indian manufacturing. To remedy this asymmetry, Nehru’s tasked a high court Judge, Justice Ayyangar to overhaul the colonial patent system.
The most crucial innovation that issued from this overhaul was the process patent regime. In brief, process patent protects the process of manufacturing, and not the final product. In other words, competitors are allowed to innovate a different process to manufacture and sell a previously patented drug. This was a crucial innovation for Indian science and technology. Recently decolonized, indigenous capital could not compete with global long-established Euro-American pharma. However, India did have a large labor force and a new crop of expert scientists at it disposal. In just 30 years, Indian pharma grew from about 2,200 manufacturing units to 20,000 manufacturing units across the country. Not only did this new industry satisfy domestic consumption, but it also became a major exporter of drugs to the global south. For example, 80% of the HIV-AIDS medicines dispensed by Doctors Without Borders across Africa are made by the Indian generic industry. For this, MSF famously refers to the industry as the “pharmacy of the global poor”.
However, the years of postcolonial protections would come to an end in 1995. Under the sign of a finance capital crisis (even though the industrial and agricultural sectors were robust) India took a loan from the IMF and joined the WTO. The WTO came packaged with new IP laws, commonly known as TRIPS. TRIPS demanded the reversal of Ayyangar’s process patent regime, and a re-implementation of colonial-era product patents. In effect, this meant that India could no longer produce generic versions of any drug discovered after 1995, for a period of 20 years after the original patent.
Famously, the first big test for TRIPS came from Swiss owned Novartis, and its most profitable drug: Gleevec. As one of the first anticancer therapies to target particular cells, Gleevec was a paradigmatic advance from earlier chemotherapies. For this, Gleevec immediately made it to the cover of Time.
In 2007, Novartis sought to deploy the new TRIPS regime, to block Indian companies who were manufacturing the drug for a fraction of its branded cost. Even though Gleevec had been discovered before WTO came into place, Novartis argued that it had since tinkered with the drug to increase its bioavailability. It then went on to argue that this increase in bioavailability was sufficiently innovative to deserve new, post-WTO copyright protections. Novartis was confident of this strategy because it had already re-patented the drug in 40 other countries.
While this case made its way through several Indian courts, in 2012, the Indian Patent Controller – P.H. Kurien (or Bullet Kurien, as he is affectionately known) revisited the Ayyangar Report. He did so to issue the first compulsory drug license in Indian history. It was a move that would garner him global praise; I’d wager that he is one of the few patent controllers to have fan art dedicated to him.
What made this never-before used clause from the Nehruvian era so controversial in the 21st century? Compulsory licenses are an involuntary contract between a willing buyer and an unwilling seller, imposed and enforced by the state. In effect, Kurien’s compulsory license forced Bayer to allow an Indian drug maker to copy and domestically sell its highly profitable liver and kidney cancer drug – Nexavar. Cannily, Kurien realized that the WTO agreement had not voided this particular provision within Ayyangar’s legislation. If you recall the opening of this talk, this is precisely the ruling that earned Bayer CEO Marjin Dekkers’ ire. Thus, if the Gleevec judgment had blocked the extension of an older patent, the Nexavar order was more radical. It made possible the voiding of exclusive rights in India for a drug well within its patent lifespan.
Fascinatingly, in response, Bayer and Novartis mounted a remarkably similar attack on the legitimacy of Indian scientific and regulatory actors.
- First, Novartis contended that the Indian court’s loose definition of what constituted scientific inventiveness was not compliant with global laws and norms. As such, it was a contravention of the spirit of the WTO, and was in violation of India’s international trade obligations. And if Novartis attacked the criteria of scientific inventiveness, Bayer condemned the compulsory license as inimical to incentives for scientific innovation.
- Second, Novartis argued that the Indian Controller General of Patents was not competent to understand the criteria of inventiveness and creativity in drug development. In language reminiscent of the colonial period, the corporation painted him in the trope of the Oriental Despot. I quote: “Such misunderstandings of scientific innovation allow the Controller General of Patents uncontrollable discretion, thus leaving companies to the mercy of his whims and fancies, and the arbitrary exercise of his power.”
- Third, and finally, both corporations made the following claim: that such legal and scientific inadequacies discriminated against their corporate personhood, violating their fundamental rights under the Indian constitution. This was an invocation of Article 14 of the constitution that defends against racial, caste-based and sexual inequality.
However, In the end, while Bayer and Novartis shared strategies, they also shared defeats. Both cases would make their long and winding way up to the Supreme Court. Novartis’ case would be denied in 2013, while Bayer’s fell through in 2014.
Remember Dekker's concern about drug copyright infringements? Dekker’s was not concerned with the loss of Nexavar revenue in India; as he had candidly revealed, Indians were not the primary market the company had in mind in the first place. However, as we see next, what is significant about the Nexavar ruling is that it reanimated a specter of global south alliances during the HIV-AIDS epidemic that had rattled Big Pharma to the core.
Lessons from the HIV-AIDS crisis
During the AIDS epidemic, the Nelson Mandela government had formed an alliance with India and Brazil, to export and import generic AIDS therapies across their national borders. Specifically, the South African government issued a compulsory license that declared AIDS to be a national emergency, and thus exempt from WTO restrictions. This compulsory license had the powerful support of HIV-AIDS action groups across the world, at a scale unprecedented for health activism.
For Big Pharma at the time, such a compulsory license was not just the loss of a single market. An alliance such as this brought a global patient pool into play, and with it, fears of global mobilizations leaking into Big Pharma’s primary Western markets. Thus, a large Big Pharma coalition including Bayer and Roche, sued Nelson Mandela personally for contravening WTO patent laws. In this, they were backed by the Clinton Administration, who threatened to raise tariffs and restrict trade between the two countries. Undeterred, South Africa began importing the drug from India, and fortunately, with presidential elections in the horizon, several key US politicians made a dramatic volte-face on the issue. Within weeks, the price for HIV-AIDS therapies fell to a fraction of the original cost. Soon after, Brazil approached Big Pharma with a threat of similar compulsory licenses. However, they did not have to carry out their threat; this time, global corporations pre-emptively agreed to drastic price cuts. To return to India, this is precisely why the Nexavar ruling is so significant. By issuing the first compulsory drug license in Indian history, Bullet Kurien had precisely invoked this techno-political tool of global south sovereignty.
If only they had known to look, these challengers to Big Pharma IP could have found an ally in the most unlikely of places: Brian Druker. Significantly, Druker, who never made money from the drug, attributes its discovery not to a single moment of inventive epiphany, but to years of research, that had no particular end goal in mind.
Specifically, his discovery narrative goes all the way back to the 19th century, and begins with a description of a CML by Rudolph Virchow. He further claims multiple lineages of research for the inventive process leading to Gleevec. For example, one of many parallel beginnings is research on the rous sarcoma virus in the early 20th century, that clarified the mechanisms of CML. And further, Druker had to fight against all odds to convince pharmaceutical corporations to develop the drug and take it to trials. Druker’s imagination of the scientific process tends towards, but not quite approaches, old notions of an inventive commons. There is some irony worth nothing here. Lawyers, corporations and the US government pushing for stricter global patent regimes describe their work as a public good - in protecting the rights of scientists and researchers and the American culture of innovation. With Druker, we find that often scientists and researchers themselves do not share the view that smaller profits jepoardize research and innovation, and that other motives such as improving health equity might be equally important in stimulating science.
At this point of the story however, we see a dramatic turnaround. While patient advocates readied themselves for another protracted legal battle, Roche surprised its watchers by letting its Indian patent on Herceptin lapse.
This change of heart has both confused and elated intellectual property watchers, some proclaiming the same victories for cancer patients that had been hard fought for and won for HIV-AIDS patients two decades ago. But before we celebrate any possible mea culpas on the part of Roche, let me offer my explanation, which is much less optimistic, more cynical, but also perhaps, more convincing. As I mentioned earlier, the drugs that I have discussed in this paper comprise a new cohort of targeted therapies for cancer. They draw upon advances in genetics and proteomics to interfere with the mechanism of cell reproduction at the molecular level. In sum, they are called biologics or biopharmaceuticals. However, in this world of targeted biologic therapies, Herceptin occupies even more hallowed ground. In other words, even though Gleevec and Nexavar are targeted biologic therapies, they are still part of an older paradigm of small molecules: organic compounds synthesized through classic biochemical reactions. Herceptin, on the other hand, is a large molecule drug made through recombinant DNA technologies across animals and humans.
Thus, Herceptin is part of the newest of the new class of drugs - large molecule biologics - that are at the frontier of contemporary life sciences. Large molecule biologics are characteristically much more sensitive to changes in the manufacturing process. Since no two cell lines are the same, since the science of protein-engineering takes thousands of steps, and since generic manufacturers do not have access to the original cell lines to begin with, they cannot produce exactly the same product. In sum, if small molecule drugs revealed how they came to be manufactured, biologics are unstable and shifty organisms, and do not disaggregate to stable and universally available components or processes. See for an example an Amgen graphic that explains biosimilars through the metaphor of snowflakes: no two are exactly the same.
Biologics shift the controversy away from intellectual property rights, and towards the politics of globally tiered scientific capability. Rather than fight battles over intellectual property, battles Big Pharma has often lost, they have begun to fight generic companies on the question of manufacturing quality and technical expertise.
Over the last two years, the challenge that this reformulation from patents to quality poses has become starkly clear. For example, when Roche let its patent on Herceptin in India lapse, Biocon and Mylan – two Indian manufacturers – began selling biosimilars of the drug for a fraction of Roche’s price. However, in 2016, Roche launched a lawsuit to deny the biosimilarity of Biocon’s product, raising questions about quality control, safety and efficacy. Importantly, Roche was not contesting whether Biocon and Mylan had infringed their patent. Rather, they were putting into doubt the very fact that the copy had any relation to the original at all, and whether the generic companies had the right to market their versions as similar to Herceptin. Unlike generics – for which the regulatory guidelines are fairly clear – there is no clarity in most parts of the world about what constitutes a viable biosimilar.
It is this space of uncertainty that Euro-American pharma is trying to define to their own advantage. Yet, this space of uncertainty resists easy clarification. The Delhi High Court responded first by agreeing with Roche and discredited the biosimilars, barring Indian manufacturers from calling their products as biosimilar to Herceptin. A year later – in mid-2017 – a division bench of the court over-ruled the individual judge’s verdict, allowing the generic manufacturers to not only claim biosimilar status, but also claim the drugs usefulness for two additional types of cancer. It also lifted the original order’s mandate to generic manufacturers that they conduct their own safety and efficacy trials, and not use those already conducted by the original corporation.
Duplicating safety and efficacy trials are not only difficult for smaller manufacturers, they also put hundreds of new cancer patients through trials for drugs that have already been tested elsewhere. Cori Hayden’s work on the generic industry in Mexico already demonstrates how making finer and finer distinctions about quality has become a key global pharma strategy for discrediting generics. The innovation of biosimilars gives this technical-political tool an entirely new power and meaning. If Indian biotech firms are able to successfully develop biosimilars, they will face a new set of challenges on this reformulated terrain of quality and expertise. In turn, the medical community’s response has been ambivalent; some have celebrated biosimilars, while others warn of their potential danger.
What does all this have to do with the Covid-19 vaccine?
The Pfizer and Moderna vaccines are part of this controversy. They are part of the same new class of drugs - biologics - that have been made possible through new genetic recombinant technologies. What this means is exactly like the drugs discussed here, big pharma in the global north will claim that they, and only they, can make the vaccine safe, effective and of sufficiently high quality. This means an oligopolic concentration of intellectual property, high prices, and bad news for global access to life-saving drugs.
If the history of drugs tells us anything, then, it is this: that the battle over vaccine access will not be about patents. Instead, it will be about quality, with a few global north corporations claiming that only they can make these vaccines safe and effective. The battle over these vaccines will not be about patents (as they were with HIV-AIDS drugs). They will be about who we trust to manufacture them. Would you take a biologic highly-complex vaccine produced more cheaply by an 'Indian' corporation, or will you only trust the quality of those produced in the United States? The answer to this question tends to play to the advantage of Big Euro-American pharma.
In fact, both Pfizer and Moderna seemed to have learned the lesson from the 1990s well: that price gouging in the middle of pandemic is bad PR. Moderna has gone as far as to promise to not enforce their patents during the Covid-19 pandemic. But, to be clear, this step alone does little to expand vaccine access. This only means they will license out their patent temporarily to other manufacturers for the duration of the pandemic. Licensing fees by themselves could ensure the drugs are beyond the reach of the global poor.
In fact, when the issue of patents really come down to the ground, Euro-America has stood firm in its resistance to relax any global patent regimes.
Further, temporary no-enforcement has to be weighed in relation to how the global north is going to disproportionately benefit from the vaccine.
The equitable distribution of vaccines depends largely on the availability of vaccines in sufficient quantities. The past few months have seen frenzied attempts at vaccine stockpiling by higher-income countries through numerous bilateral pre-purchase agreements. According to Global Justice Now, 82% of the Pfizer’s 1.35 billion vaccine stocks to be made available till the end of 2021 have been pre-booked by the UK (40 million), US (100 + 500 million), EU (200 million), Japan, and Canada, which represent only 14% of world population. Moderna is not far behind, with 78% of its vaccines sold to (largely the same) countries representing 12% of the people. AstraZeneca too has committed 100 million doses to the UK. This aggressive buyout strategy triggered by ‘vaccine nationalism’ is propelling the world towards exactly the kind of medicine trade war that experts feared when US bought up nearly all of the world’s Remdesivir supply earlier this year (discussed here). High efficacy rates and no-patent enforcement pledges would be of no benefit to countries in the Global South if they are forced to scramble over leftover supplies after rich countries have hoarded up their buffer stocks.
There is a second question at play. Covid-19 could not have come at a better time for big drug manufacturers. They have been developing the radically new mRNA based technology behind the new vaccines for since 1975. However, as will all new kinds of drugs, they have not had the opportunity to build mass public confidence in this new technology.
From an execution standpoint, success of the mRNA COVID vaccines could pave the way for future therapies in the infectious disease space and potentially other mRNA therapies, including the therapeutic candidates that Moderna has steadily developed since 2010. With its current pipeline and patent portfolios, Moderna appears to be very well positioned to capitalize on such downstream markets.
These are then the lessons from past battles worth paying attention to now:
1. Watch out for debates and racialized claims about which corporations and which countries can make the vaccine safely and effectively. While the question of whether biosimilars are equivalent to generics is tricky, it is not insurmountable. The right legal and public health regulations about how these drugs are marketed would go a long way in leveling the playing field, breaking the current oligopolic control over Covid-19 vaccines.
2. Remember that the promise by big Euro-American Pharma to not implement patent rights does not mean they will not hugely profit by licensing it out to others. It also leaves the global poor to the board-room decisions of individual pharma corporations. In fact, it goes against the global policy changes that countries like South Africa and India are fighting for and being denied. These are emergency, temporary amendments during the pandemic that would put the matter in the hands of global south governments and not Euro-American corporations.
3. Most importantly, remember that this pandemic has offered big Euro-American pharma to establish a whole new patent regime based on a new class of drugs whose future profitability looks very promising. The pandemic has afforded them the opportunity to establish patent claims that will have long-term negative repercussions on drug access for all but the richest few.
"Prior to the development of their vaccines, [mRNA] was a completely untested, unchartered mechanism of action for a vaccine, so it seems like Moderna and Pfizer are on track to get a bunch of pretty broad patents covering mRNA vaccines generally," said University of Illinois College of Law professor Jacob S. Sherkow. "Some of the intellectual property foundations that are being laid now are going to play an increasingly important role with respect to the development of vaccines in the future."