The medicines of the future must be sustainable!

I work a few days in the middle of July and give myself the opportunity to dive into an area that has repeatedly knocked on my door, but I haven't really had the nerve to open. Maybe it'll be a belly splash, but I'll make sure I get really wet, which means I've gained new perspectives and maybe some knowledge too. Welcome to join me on my swim, if you feel like it.

You don't have to google long to understand that the area is hot, both on a national and international level. LIF, the research research-based pharmaceutical industry in Sweden, recently published a roadmap for a fossil-free pharmaceutical industry. Another example is Health Care Without Harm, a global partner network, which, among other things, has published a roadmap to reduce the carbon footprint of the entire health care sector on a global level. This sounds good, roadmaps mean there is a direction and also goals. You can't set the GPS and calculate how long the trip will take or which way to go if you don't know where you're going. But do we know for sure where the journey begins?

According to figures that  the World Economic Forum refers to, the healthcare sector, including pharmaceuticals, accounted for 4.4 % of the global net emission of greenhouse gases (2019). It is a lot. Especially when you consider that the climate crisis is actually the single biggest threat to our health.

In Sweden  pharmaceuticals account for just over 3% of the health care's climate footprint, a low figure compared to how it looks in many other countries. I think that it could be due, for example, to the fact that many of the global pharmaceutical companies do not have their production located in Sweden. It may also be the case that companies in the early phase move their later development to production facilities abroad. A third suggestion is that the proportion of biological medicines, which might not have as severe climate impact, is proportionally greater in Sweden than in some other countries.

Yet, however it is, we cannot sit down and blow our minds and think "we can take it easy, the problems are not that big in Sweden".

I see that there are two overarching reasons why Sweden should take international responsibility for sustainable pharmaceutical development and production.

1. Sweden is good at pharmaceutical development and since the value chain is global, from the supply chain, development and production to clinical trials, distribution and implementation, all countries and actors involved must contribute to the whole, not just "their" part.
2. Sweden is good at Green transition and bio-based raw materials, which can be applied in many different areas.

Vinnova (i.e. the government) also thinks that Sweden should take a big responsibility for the green transition, as there are several calls for proposals in the area. The new program Impact innovation, for example, calls for health solutions within the planet's boundaries. Another example is European innovative health initiative (IHI) which recently published a preliminary topic for an upcoming call ( IHI call 4 — topic 6 ). Innovations that will contribute to the sustainable development and production of healthcare products, including pharmaceuticals, are requested here. These are really questions that I am passionate about and that we at RISE are working on. But I need to understand a little more. We need to find project partners who are also passionate about these issues.

So, what is sustainable drug development?

It is now that the direction of my swim starts to become diffuse, it feels more like I ended up in a bubble bath. I find many different reasonings and definitions and try to create some kind of consensus. An overarching vision is "health for all, within the planet's boundaries ". Health comes first, the planet comes second, is that how we should look at it? I think it is quite human, if there is an opportunity for treatment, we want to take that opportunity. But the perspective is changing, and the health of the planet is beginning to weigh more heavily. Many have noticed, for example, that medicines containing Diclofenac (which has environmentally hazardous properties) are no longer sold without a prescription at the pharmacy.

But which perspectives are most important to take into account? It is now that I experience the benefit of diving into a new area. I escape the expert's weight belt that pulls me down to the bottom and my naivety and curiosity fills my diving vest with air and keeps me afloat. I also have the advantage of being surrounded by a great many experts whom I can connect to the issue.

My list of the most important perspectives for sustainable pharmaceutical development within the planet's boundaries

• Minimize the use of non-renewable raw materials, such as fossil carbon sources
• Reduce greenhouse gas emissions
• A non-toxic environment and One Health
• Do not affect the planet's ecosystem (e.g. pharmacological or genetic effects and side effects)
• Only develop medicines with sustainable water and energy consumption

Now it's about finding, or choosing, points of attack where we can get better. Some are simple and perhaps obvious, others are more challenging and perhaps very costly. Here we need to share the responsibility; consumers, producers, financiers and decision makers. Laws and regulations can help. Research, innovations, and new ways of working are needed.

What can we do today?

We need to work together towards common goals. It is about optimizing the development process as well as understanding the environmental impact of the entire value chain. A couple of examples where RISE has expertise and projects are in the optimization of manufacturing processes in organic synthetic chemistry and in the analysis of substances in waste water and in various biological samples.

In my summer reading and deep diving into the area, I have realized that there is a lot of literature and knowledge, yet not enough is being done. Below I list some points that I think are self-evident.

• Make sure that your drug molecule only affects the target structure (receptor, cell or other structure) that it is aimed at, to reduce the risk of unwanted effects on the ecosystem.
• Aim for a low treatment dose. So that there is not a large excess of medicine in the body, which is urinated out and spread in the environment and affects other organisms in the ecosystem.
• Do not build in known environmentally harmful groups (eg PFAS) into the design of the medicine or into the production process.
• Let biodegradability or transformation be an important selection criterion when choosing a drug candidate. Persistent, bioaccumulative and toxic (PBT) substances must be avoided.
• Create sustainable production processes by avoiding or replacing environmentally hazardous solvents, creating circular processes and reducing waste. Energy consumption and water consumption should be limited through more efficient processes.

Even on the user and implementation side, there is much that can be done to protect the environment and save the planet's resources. A few examples are:

• Only use drugs that have a chance of working in the patient being treated. It is about tailor-made medicines (precision medicine), but also about the right diagnostics, resistance and development of antibodies that remove the effect of the medicine, so-called ADA (anti- drug antibodies).
• Reduce drug wastage, leftover drugs

Going forward, innovations and new ways of working are needed

We talk a lot about the possibilities of digitization and artificial intelligence (AI). Drug development is indeed an area where AI can be used to accelerate the development of chemical processes and drugs . This area, which is under development, has great potential to contribute to reduced energy consumption, CO₂ emissions and consumption of finite resources.

The origin of the drug substance is of importance

If the drug product is biological, such as a peptide or an mRNA vaccine, then there are probably not excessive risks of it being toxic in the environment, as it falls apart or breaks down. But other biological products, such as the hormone estrogen, have a major impact on the ecosystem. In addition, many biological manufacturing processes require relatively large amounts of water, the most important resource on our planet.

A chemical, low molecular weight medicine has probably been produced from fossil carbon sources, i.e. oil. This is not sustainable in the long run. As I wrote at the beginning, other areas are moving towards green chemistry and are testing, for example, residual streams from the forest industry as a source of activated carbon in various chemical syntheses. Is this also possible for pharmaceutical production? My experts don't say no, they have the knowledge to start unraveling the problem, but it costs money to develop new processes. Is the pharmaceutical industry and ultimately the consumer willing to bear that cost? Can we afford not to?

I jump out of the hot tub and ask myself, was this a wild fantasy dream?

—No, it's not just me swimming around in a thought bubble, the articles I've found and the calls for project proposals that are coming show that the area is now hot. I think the time is ripe for us to jointly develop new medicines where the health of humans and the planet is protected at the same time.