A dose of their own medicine — should SA force big drugmakers to let others make insulin pens too?

15 Aug 2024

Novo Nordisk’s deal with local manufacturer Aspen to produce insulin in vials aims to supply the diabetes treatment for Africa, but critics say it doesn’t deal with the real issue: South Africans have a right to use insulin pens, but these are running out in public hospitals because of Novo Nordisk’s decision to not tender to sell it to the Health Department anymore.

In 2023, Danish pharmaceutical company Novo Nordisk announced a deal with local drug manufacturer Aspen to produce human insulin in vials on their behalf for Africa.

But, says human rights lawyer and founder of the Health Justice Initiative Fatima Hassan, “they’re trying to frame this licence as progressive, but Novo Nordisk’s restrictions are taking us to the Dark Ages”.

Insulin is a hormone produced by the pancreas and controls blood sugar levels by helping cells absorb glucose for energy. If someone’s pancreas doesn’t make (enough) insulin they have a condition called diabetes and may have to inject themselves with a lab-made hormone called human insulin to mimic the body’s natural sugar control system.

Novo Nordisk says it aims to make enough insulin for just more than one million people in Africa (about 16 million vials) by 2026 – at roughly R45 ($3) a pop.

About 24 million people in Africa have diabetes, set to at least double in the next 20 years, but only about 1% of what the world pays towards diabetes care is spent in Africa.

The snag, though, is that the medicine will be made available in vials, not injection pens. These pens, which are plastic tubes filled with insulin, have a disposable needle on one end and a dial on the other. Turning the dial makes a clicking sound as it passes numbers in the dosing window, which helps a user set the exact amount of medicine for injection. This makes it especially convenient for users such as the elderly, who may have arthritis in their hands, or people who can’t see well.

But since May these pens have been running low in South African public hospitals and clinics after Novo Nordisk decided to stop supplying the Health Department because of “capacity limitations”.

This means many of the country’s diabetes patients have no choice but to switch to syringes and vials, which take many steps to prepare for injection, as public hospitals ration the remaining pen supply to people who can’t safely switch from pens to vials.

Putting patients in this position is “unconscionable, unconstitutional and a clear abuse of intellectual property rights”, says Hassan.

What is South Africa going to do about it?

Aspen’s contract with Novo Nordisk is to complete the fill-and-finish stage of insulin production, which means the local pharma company will fill the vials with medicine and finish packaging it.

Aspen will get the insulin in powder form from Novo Nordisk’s Denmark facilities, dissolve it in a watery solution that has a chemical make-up that’s similar to that of blood, pour it into vials, do quality checks and finally label and pack the bottles in boxes. Novo Nordisk will then collect the boxes and distribute them, explains Aspen CEO Stavros Nicolaou.

Following the announcement of the deal, the Department of Trade, Industry and Competition said it was an “excellent first step” towards manufacturing refills for reusable insulin pens, which are in short supply in the public sector. For South African manufacturers to do that they may need permission from the company that holds the patent to make and supply them, called a voluntary licence.

In response to Bhekisisa’s questions about the further licensing for insulin pens, Nicolaou says he can’t predict whether Aspen will be able to make pens in the future. The vice-president and general manager of Novo Nordisk South Africa, Sara Norcross, says the focus of their new partnership with Aspen is to increase the supply of affordable insulin in Africa.

Novo Nordisk has a strong stance on intellectual property rights, according to the company’s website. It says that because making new drugs is expensive, recouping the investment is important so that they can continue to make more lifesaving medication. For this reason, and because they already “sell human insulin at low prices through large government tenders” in many low-income countries, the company is against voluntary licensing.

This is where the Patents Act may come in.

If companies abuse their patent rights by not meeting the country’s demand for a specific product – such as insulin pens – or refusing to grant a licence on reasonable grounds, the commissioner of patents can issue a compulsory licence to other manufacturers via a court process, which allows them to make the product without the inventor’s permission.

These laws are based on an international contract called the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (Trips Agreement), which gives governments tools to tackle intellectual property issues.

Hassan says South Africa needs to use them.

“This deal is insufficient to meet South African needs [for insulin pens]. Both Aspen and Novo Nordisk are remiss in their obligations to the people of this country. The real question now is: what’s the government going to do about it?”

A recipe for success

Compulsory licences, however, aren’t a silver bullet, says senior lecturer in pharmacology at the University of KwaZulu-Natal, Andy Gray. These licences have never been issued in South Africa, though, partly because it’s a long, complex court process and the high cost that comes with it blocks people from filing applications for them.

But even with such forced permissions, local manufacturers would still need a supplier for the insulin.

In 2019, more than 90% of South Africa’s insulin supply came from three multinational companies – Novo Nordisk, Eli Lilly and Sanofi – none of which have manufacturing sites in southern Africa. “There is no production facility for insulin in South Africa, so we mostly import the product,” Gray says.

Insulin used as medicine is a biologic drug, which is different from a chemical one because it’s made by a living cell rather than through a series of chemical reactions. The sugar-control drug is produced by putting the gene for insulin into a ring of bacterial DNA, inserting the altered DNA into a specific type of microbe (such as bacteria) and then using them as tiny insulin-producing machines. This gives rise to a product called recombinant insulin, which is difficult to copy because of the way it’s put together.

But with the 2021 launch of the mRNA Vaccine Technology Hub in Cape Town, which makes biologic vaccines by using short lab-made gene sequences to instruct your body to make proteins to fight a particular virus, Gray says insulin production could someday be on the cards for South Africa.

However, big pharma companies that make insulin keep their recipes for the process secret.

The general method for making insulin – in other words, the hormone itself – is well known, but it is tricky to mix it into a final drug form that can be used as medication. That means any small changes in the steps or materials used in this process can affect how well the medicine will work.

The method followed in this process belongs to the original pharmaceutical company and is protected by trade secret laws, which, unlike patents, never expire, Gray says. A trade secret is confidential information like a lipstick formula or a manufacturing process that gives a company a competitive edge – and they can’t be forced to share it. It also means that their process can’t be copied by another manufacturer unless those researchers figure out the steps on their own.

For example, during the Covid-19 pandemic, the pharmaceutical company Moderna made all the information about the building blocks of their vaccine public, but local scientists still had to use their expertise to figure out how to put it all together to make a copy of the vaccine. To save them the trouble, a technology transfer process, where the original developer shares its trade secrets and expertise, would have helped.

Producing insulin in injection pen format adds another layer of complexity, as many international drug companies, like insulin pen producer Sanofi have patents on the injection device itself, meaning that local drugmakers must either design their own injection pen or get a licence to make it.

Don’t bite the hand

Some countries have used compulsory licensing not only to sidestep the excessive pricing of lifesaving drugs, but also to negotiate voluntary licences for a reasonable fee.

In 2007, for instance, Brazil prepared two compulsory licences so that generic manufacturers could make antiretrovirals (ARVs) to treat HIV and sell the drugs to the government cheaply in order for them to be given for free to people through a national HIV treatment programme. One of these licences resulted in generic versions of efavirenz being made available at about R1,200 ($170) to treat one person for a year instead of the R5,400 ($760) deal offered by the pharmaceutical company Merck.

But the Brazilian government decided to hold off on issuing a compulsory licence for the other ARV, lopinavir. The threat of a compulsory licence alone was enough to get the manufacturer, Abbott Laboratories, to offer a 57% discount on the price – down from about R23,300 ($3,241) per person per year to just under R10,000 ($1,380).

It may be difficult for other countries to get the same results, though, because Brazil is a fairly rich middle-income country with bargaining power thanks to its pharmaceutical manufacturing facilities and knowledge about reverse engineering drugs and so produce copies of them.

Some countries may also shy away from compulsory licensing from pharmaceutical companies because it could lead to a backlash from rich countries.

“Pharmaceutical companies have a lot of power in terms of wealth and influence,” explains Phumudzo Munyai, head of the mercantile law department at the University of Pretoria.

“A patent is a form of property and if a government is going to force companies in the Global North to give up their property without asking their permission, it could cause damage to our trade relationships and the economy in general.”

For example, in 1997 South Africa passed new laws that would allow the government to use compulsory licences and import more affordable generics of ARVs from other countries to fight the Aids epidemic.

This led to an application by the Pharmaceutical Manufacturers Association and 41 drug companies at the Pretoria High Court in 1998 to oppose these new measures, arguing that it violated the constitutional right to not be deprived of property.

The US Trade Representative, an American government agency responsible for trade policy, then placed South Africa on a “watch list” for countries that needed to change their intellectual property rules that could result in their trade relationship ending.

Eventually public pressure from international media and civil society, most notably the Treatment Action Campaign, forced the US and the pharmaceutical companies to back off.

By August 2001 the price of original branded products, which at the time cost more than R80,000 ($10,439) for one year’s treatment per person, dropped to about R6,000 ($712) after competitors were allowed to make low-cost versions.

“The threat of compulsory licensing marked the beginning of reasonably priced ARVs. It was basically a gun to their head,” explains adjunct professor at the Wits School of Governance, Alex van den Heever.

“This is what the Department of Health should be doing to provide access to insulin pens. In times like these, the government can’t afford to just sit on its hands,” he says. DM

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.

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What is South Africa going to do about it?

A recipe for success

Don’t bite the hand