Lonza Expands the Boundaries of Sub-Cutaneous Injections
Innovations in formulations and injection devices improve compliance and quality of life for patients using new antibody formats.
The field of biologics is undergoing a significant change as it increases its focus on identifying new diseases to target, novel constructs to treat those diseases and innovative administration devices that include self-administration technologies to improve compliance and patient quality of life.
Patients who have diseases that demand regular administration of these new antibody treatments, on a monthly or bi-monthly basis, will see the significant benefits from these self-administration innovations, as their lives will not be highly impacted from constant travel to the doctor or the hospital. These formulation and device innovations will also have a positive impact on how well patients are able, or willing, to comply with the administration schedule as it becomes less disruptive to their lives.
The goal at Lonza is to support our customers who are breaking new ground in biologics by supporting them in the development and manufacturing of their target drug product profile, ensuring that their patients are receiving the right dose of a stable drug product using an easy-to-use device. To achieve these goals, there are important aspects to consider.
- High-concentration formulations are typically required for these treatments, which come with a range of technical challenges.
- The drug and the formulation must be compatible with special container closure systems.
- The functionality of the drug/device combination product must be ensured so that the dose can be delivered safely and effectively.
As noted earlier, producing high-concentration formulations presents some important technical challenges. These formulations have a tendency towards association and aggregation due to macromolecules crowding, which can result in aggregation and the formation of subvisible and visible particles. So, the stability of the formulation is very important.
In addition, high-concentration formulations tend to have a high viscosity due to reversible self-association leading to the formation of large networks/meshes that resist flow and increase viscosity. As these high-concentration formulations often need to be self-administered, they must have the right viscosity (a viscosity which will allow for reasonable “syringability” and injection time). It’s important to manage this balance during the formulation development, in order to find the sweet spot of concentration, volume and formulation design space that will ensure both adequate viscosity and stability of the formulation.
Our experience in balancing concentration, volume and formulation design has led us to begin recommending to our customers that they consider these important variables early on when selecting molecule candidates. Molecule candidates can not only be screened for their pharmacological activities, but also with regards to their physico-chemical properties or their developability, including the tendency to self-associate that can lead to aggregation and/or increased viscosity.
While developing a safe and effective formulation, it is also important to evaluate the compatibility of the drug product formulation with the container closure system. For self-administration (usually prefilled syringes or cartridges) these devices come with a special material for contact with the drug product. For instance, the inner wall is usually coated with silicone oil to facilitate “syringeability.” Interaction of the protein with silicon oil can produce protein aggregates or rub-off silicone oil from the syringe wall, leading to an unreliable injection. Moreover, there can be traces of heavy metals from the manufacturing process (e.g., Tungsten oxides) that can induce drug product degradation. These risks should be carefully investigated, and mitigated for, during formulation development.
We have done a great deal of research and testing for products that allow for self-administration and home use. In order to have a safe and reliable self-administration package, it’s necessary to develop a device that can reliably deliver the protein solution. For prefilled syringes, Lonza has worked to set up the respective technologies for measuring the integrity of the plunger, the needle tip, and the functionality of the device.
In fact, when it comes to innovation in the injection devices, Lonza has focused on to how to solve for the increased interest in moving to higher and higher overconcentration. One could use viscosity-reducing agents (depending on the molecule properties and molecular weight) to reduce the protein’s self-association and push the concentration up to 180 to 200 mg/mL. We learned that, when the physical limit of packing hard spheres is reached, there are basically two options: use a device that can handle higher viscosities or deliver volumes of up to 5 or 10 mL. To meet the challenge of delivering higher volumes, Lonza collaborates with Ypsomed on the YpsoDose wearable injector that can deliver up to 10 mL, enhancing the volume (and dose) that can be self-administered by patients.
It’s clear that one of the benefits of working with Lonza is our end-to-end approach to developing formulation and injection technologies that allow companies to develop highly-functional devices that work in concert with their drug product formulations. Our team has extensive expertise and they set up the development correctly, proactively anticipate risks and suggest mitigation measures. We have a well-established formulation platform process that helps move these products into clinics quickly, with defined risks and a good investment of resources. This holistic approach – with a focus on each of the elements necessary to create a successful, self-administered, sub-cutaneous injection – make Lonza the right company to work with for those who are looking to continue to innovate and push the boundaries of successful subcutaneous injections.
Head Formulation Development, Lonza Drug Product Services
By leveraging our own technologies, Lonza now offers more accurate Process Analytical Tools (PAT) at a reduced cost for customers
Imagine if instead of seeing glimpses of data in your process, you could see a continuous data stream?
To provide consistent, safe, and high-quality products for customers and the patients they serve, it is critical to monitor and control bioprocesses.
Current bioprocess monitoring and control schemes still rely on infrequent and time-consuming offline sampling methods. This leads to loopholes in data and major gaps in knowledge, as well as an increased cost.
Having a clear picture of the system, instead of relying on discrete snapshots throughout the day, opens the possibility to see what is really happening with the product profile.
Process Analytical Tools -- better known as PAT, a mechanism to design, analyze, and control pharmaceutical manufacturing processes – provide real time data to improve the process robustness and reduce cost.
A New Method
In order to reduce errors and enhance efficiency, while improving the quality of the product, Lonza formulated a new PAT strategy by leveraging existing technologies and R&D set-up, and bringing PAT into the digital age. This new method not only fills the gaps of previous PATs and improves the quality of the data, but also reduces the cost of the system and the initial upfront investment.
To get rid of the variability in the process during production, which may impact the product quality profile, Raman probes are used to monitor changes of critical bioprocess parameters such as cell counts and metabolite concentrations. Continuous analysis of these components enables operators and data scientists to monitor cellular metabolism and growth while providing mechanisms for continuous process adjustments to maintain nutrient levels at desired targets.Adjusting the bioprocess in this way yields a reproducible process yielding product that meets SISQP standards each and every time
Better Results for Our Customers
The key is that the process itself doesn’t change; the way in which information is obtained about the process does. Lonza is unique in that we are one of the few CDMOs incorporating a platform-based PAT strategy that can work independently, without relying on the customer process.
This results in quick wins with more accurate information. Meaning, there is no disruption to the process. Our customers get access to data from the entire process and a better understanding of how the cultures are growing. For example, when monitoring viable cell count (VCC) in real time, abnormal growth profiles can quickly be identified and flagged.
PAT of the Future
Previously, PAT had only individual data points. Now one can see the entire process, even between data points, and get a better understanding of how the cultures are growing. Better process understanding enables more robust process control resulting in fewer lost batches and higher productivity.
By leveraging existing R&D technologies and the method of customer access, we are eager to see the results of our customers’ products, without requiring the typical large upfront investment associated with traditional PAT.
Senior Manager, PS&T PAT & Automation CoE, Lonza
We help customers develop, manufacture, and innovate their small molecule medicines through our commitment to science, technology and delivery. We provide integrated drug substance and drug product services through our global site network with a strong track record of being present throughout the product lifecycle.
We are here to make a Meaningful Difference. It is the foundation of the way we do business. A career at Lonza is more than a job. We do not just work in the life sciences industries, we are transforming them. What we do today is helping to create a healthier, happier world tomorrow.