How Lonza leverages new technology to optimise efficiency and patient focus

Right now, the contract development and manufacturing organization (CDMO) industry is under considerable pressure. This is a result of the continued growth of small molecules in the clinical pipeline, and because most of the companies driving that pipeline now work to timelines which would have been quite fanciful just a decade ago. Yet the growing demand means CDMO lead times are getting longer. Assets are filling up, but customers need material to be supplied faster than ever before, to keep complex clinical processes on track.

This is the drive behind one of our key goals at 龙沙 : to find new ways to implement emerging technologies that will accelerate the manufacturing process. Can we use continuous manufacturing in the early phase, for example, to help pull material through more quickly?

In the years since I started my career in the industry, there has been a steep-change in the use of digitalisation and automation. Back then, laboratory pumps were calibrated using a stopwatch and a measuring cylinder to make sure they were flowing at the right pace. Nowadays, this can all be done in real time while the process is running.

Tools such as process analytical technology (PAT) offer the potential to improve manufacturing quality by maintaining a very narrow corridor of parameters that ensure the product will be within specification. The result will be much more efficient use of raw materials, as well as allowing products to be released more quickly.

At some of our newer-build plants, we have incorporated fairly advanced levels of process technology. As an example, there was a very high degree of automation within a custom plant we built for Clovis Oncology . This was possible because, as a dedicated plant, it was clear what would be made in it, and we designed the plant to fit a process, rather than the reverse. In the end, it was almost a pilot project for small molecules, taking us down the pathway towards real-time release testing.

For another customer, we recently digitalised the plant to give them direct access to our systems, offering a much greater degree of transparency in the manufacturing process.

Continuous manufacturing is not always the answer, of course. But in some cases it makes a lot of sense, either for safety or for quality control. With a hazardous chemical reaction, continuous manufacturing not only gives a high degree of efficiency, but there is also much better control over the material, and it removes the potential for a “runaway” reaction.

Another key trend driving the need for new technology is the sheer complexity of the molecules entering the pipeline. There are no new aspirins waiting to be developed any more. Instead, over the past 20 years, the average number of synthetic steps for a new chemical entity has risen from eight to 13.4. The molecular weight, which is a good indicator of a molecule’s complexity, has also increased by 35%. As a result, there is considerable scope for artificial intelligence to improve the efficiency of designing chemical processes to make them.

Many of these molecules also have fundamental problems in terms of low solubility. It is not unusual for a drug to come to market where the patient has to take multiple tablets or capsules a day, fordoses required to overcome solubility issues and achieve desired efficacy. At Lonza, we are developing tools to take a poorly soluble material and make it much more bioavailable. We have developed enhanced technology which allows amorphous dispersions to be created efficiently for extremely insoluble drug molecules. This has major benefits from a patient perspective, as the improved solubility of these dispersions will reduce the multiple tablets a patient has to take.

We have used this technology in partnership with a number of companies who had an inefficient dosage to market in order to get the drug to patients more quickly, before refining the delivery mechanism to make it easier for them to take. This is important in terms of driving better compliance: people are going to be far more likely to continue their medication if it is less complicated for them to take.

There is also potential in administering medicines through inhalation. Biologics are typically administered via injection or infusion, as the permeability of these large molecules is low. Inhalation offers the potential for a lower dose, and therefore a reduced side-effect profile, which could be particularly important for long-term treatments. Right now, we are looking at this approach for a number of products in respiratory tract diseases and inhaled diseases. It is a fairly new and emerging area, but one where I think we can really establish patient benefit.

But this digital pathway, where we are looking to introduce new technologies and blend them with more conventional ways of manufacturing, is a journey. We have taken many steps, and have made good progress in a number of areas. In others, we still have a way to go.

Let me know your thoughts on how we can create a more efficient patient experience.