The principles of green chemistry are becoming increasingly important to companies who make all forms of chemicals. This, of course, includes the active pharmaceutical ingredients we make here at Dapin. It’s part of the wider sustainability picture, and companies should all be aiming to reduce their environmental footprint. An important aspect of this is taking a very careful look at our chemical processes, and working out how they could be made more sustainable.
There are many things we can do – and are doing already. Fermentation processes can be ‘greener’ than traditional chemical reactions, for example. A carefully designed continuous manufacturing process using flow reactors can reduce both energy usage and waste. Digitalisation can help us optimise process conditions to make them more sustainable. And, of course, collaborations with academic groups in universities are important in developing and understanding new principles of green chemistry.
All of these provide important pointers about what we can do to improve our sustainability in the coming years. However, the fact that we work in such a highly regulated market adds to the challenge. Manufacturing processes have to be approved, and we cannot simply implement a new, greener process for an existing product without gaining further approvals from the regulators. There would have to be very good cost or legal reasons to make that change feasible.
The story is very different for new products, though. If green principles can be built in at the outset for a new process before approval, it is much easier than having to go back to the regulators for permission to make changes. If we look ahead 10 or 20 years, I believe we will start to see far more market penetration for greener processes that were implemented at the outset of a product’s journey to market.
One thing that can be improved under any circumstances, of course, is the amount of waste the process generates, and how it is dealt with. There are many ways waste can be addressed without making material changes to an approved process. Solvents are a good example. We could find ways to use less solvent in a process that would not be deemed a significant change, immediately reducing the amount of waste we generate. And, of course, the waste solvent could be recycled instead of incinerated. Even if a client were concerned that using recycled solvent might pose a purity risk, it could be used in less critical processes, or even sold.
Using enzymatic catalysts is another way to make processes greener. A good example is for a chiral synthesis – enzymes are naturally chiral, and will make only one of a chiral molecule’s two mirror-image forms. Compared to a process that makes both, the yield will automatically be higher, and there will be no need for a slow, costly and, often, solvent-heavy process to separate the two.
Another barrier to implementing green practices is the cost when traditional methods are cheaper. This is something that will require a changed mindset throughout the value chain. If the pharma/biotech company client implements sustainable practices from the outset, it will make it far easier for us as a CDMO to implement once the project advances through the pipeline and reaches us. Green chemistry can be implemented at the start.
There will always be a need to use processes requiring reagents that are less environmentally friendly. But even here, sustainability improvements can be implemented. Reaction conditions can be optimised, for example, so that less of the reagents are needed. This will also have a positive impact on the amount of waste generated, and the cost of the purification. For a catalytic reaction, a better catalyst could be found. It might be better because it makes the reaction more efficient, for example, or because it is easier to purify – it is notoriously difficult to remove all traces of palladium catalysts, for example.
The onus is on us as a CDMO to implement sustainable practices in API manufacture. However, it is also important for the regulatory agencies to recognise the growing importance, too, and support sustainability initiatives. If we develop a new, greener synthesis for an existing product that requires re-approval, we need there to be support and acceptance at an agency level. A lot of R&D functions are involved in the process, and alignment between every link in the chain – including the regulators – will be vital if we are to meet sustainability goals.
