At first glance it would seem that generic forms of insulin (versions created when patents expire) should be making a significant impact on global insulin prices and therefore the ability of people to access insulin. On closer inspection it is clear that they have not yet made a noticeable effect.
This is puzzling. After all, insulin was first in used in humans in 1922, so how could it be so expensive today? Surely the pharmaceutical market must be churning out generics by the barrel. Unfortunately, this isn’t the case. Producing insulin is much more complicated than say, making paracetamol. Rather than a simple chemical molecule, insulin is a hormone (a type of biologic medical product) and has to be extracted from a living source. This is one of the main reasons why insulin remains so expensive. Before we look at the details of modern insulin production and the issues with biosimilars (like generics, but a term specific to biologic medical products) lets look at how insulin production has evolved.
The first insulin used on humans by Banting and Best in 1922 was extracted from cows. The product from this type of process is called animal insulin. Over the years the process was refined and a method was discovered to produce it on a larger scale (usually using pigs). It was the only type of insulin available until the 1980s. For various reasons this process is expensive and difficult to scale. Another problem with this type of insulin is that it has a peak activity time up to 3 to 4 hours after injection. This can make timing meals very difficult as you need to plan well in advance to avoid big swings in blood sugars.
Human insulin was first developed in the 1960s and 70s but only came onto the market in the early 1980s. It is produced by inserting human genes into bacteria in a lab to create an insulin that mimics that which is naturally produced by the human body. The technique allows for production at a large scale. The insulin also acts significantly quicker than animal insulin which makes it easier to fit into everyday life.
Analogue insulin is a modern subset of human insulin and is created in a similar way; in a lab with genetically modified bacteria. The difference is that the analogue process goes further and changes the order of amino acids to allow the insulin to be used by the body either more rapidly or more slowly by the body than with regular human insulin. Examples of these kinds of insulin include the widely used Lantus and Novorapid/Novolog products.
Now we know the basics of what kinds of insulin are available we can look at why it is very difficult for a pharmaceutical company to copy another company’s insulin, even when it is no longer under patent.
Biosimilar insulins are basically a copy of an existing type of insulin. For example, a copy of Lantus has recently been approved for use in the European Union. Companies making a biosimilar are able to replicate the active molecules that make up the insulin that they are trying to copy. However, because making an insulin in the lab is very complicated, they are unable to replicate the original company’s process. The situation is a bit like trying to recreate a friend’s sponge cake without having their recipe. After a lot of work and time you will probably be able to make a very similar cake, but the method you use will almost inevitably be different from that of your friend.
It is worth noting that this is different to average drugs, such as metformin, which are much more straightforward to copy when their patent protection runs out. Because they are easy to copy, a company making a generic version of a simple drug doesn’t have to go through lots of human trials before they get approval from the drug regulator. On the other hand, biosimilars are complicated to produce so regulations stipulate that they need to be tested almost as thoroughly as a completely new product. This creates prohibitive costs to new companies trying to enter the market because they have to spend almost the same amount of money to produce a biosimilar as they would a novel drug. However, producing novel drugs is profitable because companies are rewarded with patents which allow them to set high prices. A biosimilar does not have this benefit.
Although there are existing regulations for getting biosimilars approved and onto the market, they vary from country to country, with even the definition of biosimilar being contested between countries. Regulations have also received various criticisms, including vagueness about how much evidence is needed to prove that a new product is similar enough to an existing one. This shows the real need to align and harmonize biosimilar regulations worldwide.
Despite these issues biosimilar insulins can be produced and do exist in a number of countries. However, the dominance of a small number of large companies persists. This is partly due to their innovations and new brands, all of which come with protecting patents and price increases. The inclination to use the latest versions of insulin is not always necessary. Simple human or animal – and presumably cheaper – insulins will nearly always suffice, especially when the alternative is no insulin at all.
The few global producers who dominate the market have been in no hurry to sell their older versions of insulin. It is interesting that Novo Nordiskwere reported to be looking to increase their sale of older insulin to the developing world at cost price. Perhaps this is a glimmer of hope that the big pharmaceuticals are realising their moral duties? The vast profits of pharmaceutical companies have recently come to the attention of the BBC, who note that as patent expiry dates approach, pharmaceutical companies may be forced to change their strategies as other players enter the market. It is too early to tell how this might affect a person’s ability to afford insulin, but we must keep the pressure on these companies because insulin remains out of reach for many across the globe.
We need to come together with one voice to demand that companies stop profiteering and increase production of older, and still very effective, forms of insulin. Perhaps even more importantly we need clearer regulation to help guide more biosimilars onto the market to provide genuine competition for the big players.