by Ahmed Besheer
Head Formulation Development, Drug Product Services

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.

  1. High-concentration formulations are typically required for these treatments, which come with a range of technical challenges.
  2. The drug and the formulation must be compatible with special container closure systems.
  3. 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.

Additional Information and Disclaimer

Lonza Group Ltd has its headquarters in Basel, Switzerland, and is listed on the SIX Swiss Exchange. It has a secondary listing on the Singapore Exchange Securities Trading Limited (“SGX-ST”). Lonza Group Ltd is not subject to the SGX-ST’s continuing listing requirements but remains subject to Rules 217 and 751 of the SGX-ST Listing Manual.

Certain matters discussed in these articles may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these expectations and estimates will be achieved. Investors are cautioned that all forward-looking statements involve risks and uncertainty and are qualified in their entirety. The actual results may differ materially in the future from the forward-looking statements included in these articles due to various factors. Furthermore, except as otherwise required by law, Lonza Group Ltd disclaims any intention or obligation to update the statements contained in these articles.

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