Primary Packaging Selection: The Pathway to Successfully Developing Drug Products for Homecare or Self-Administration

Key Factors in Primary Packaging Selection for Biologics

In general, selecting the right primary packaging involves a comprehensive evaluation of multiple factors, including formulation type, route of administration, required dose, dosing frequency, and drug characteristics. Each consideration impacts the overall performance and usability of the final drug product. The basis for every drug product development is the unique target product profile (TPP) of the biologic drug, which contains the key factors that need to be considered and defines the development roadmap that will be followed.

Biologic Drug Formulation Types

The type of drug formulation—liquid, lyophilized, or frozen—dictates packaging requirements.

For lyophilized formulations, the container must first support sublimation during the freeze-drying process, afterward provide appropriate protection of the dried product from moisture, and finally allow for easy reconstitution.

For frozen formulations, the primary container must withstand (ultra-)low temperatures without cracking, breaking, or compromising container closure integrity, necessitating robust materials like reinforced glass or polymer materials.

Route of Administration

The route of administration also plays a critical role in primary packaging selection.

Biologics are primarily administered through intravenous (IV) infusion or subcutaneous (SC) injection. The choice between these routes is often influenced by the drug indication, its required dose and dosing scheme, the nature of the drug, and patient convenience.

IV infusion is primarily performed in a clinical setting, e.g. for very severe and active diseases and when a high direct bioavailability is needed. IV drugs typically use vials as primary packaging and are then diluted into an appropriate dilution medium in infusion bags to reach the required dose for the patient.

Administration of a drug by intravenous infusion can take several hours. This dosing approach greatly inconveniences the patient, especially for chronic diseases, where regular and continuous treatment is needed. In such cases, SC injection is generally preferred for home care application or self-administration. SC injections require smaller volumes, which leads to dedicated smaller packaging formats, such as pre-filled syringes or cartridges. The selected packaging must maintain drug stability and ensure safety, as well as correct and easy usage. To that end, the primary packaging is typically combined with a device, like an auto-injector, pen, or on-body device, ensuring the drug can be seamlessly administered at home.

The Shift Toward Self-administration

For many of today’s biologic drugs, such as monoclonal antibodies, the route of administration will commonly be subcutaneous injection, either as a development goal from the start, as a late-stage, or even lifecycle management change. This trend reflects the growing emphasis on patient convenience, which helps to improve patient compliance and reduces healthcare system costs. However, it presents unique challenges in drug development.

Moving therapies to a home setting and subcutaneous administration demands much smaller volumes, necessitating higher concentrated formulations to deliver the same dose as an IV infusion. Subcutaneous injection also necessitates innovations in primary packaging materials and device design to accommodate higher viscosities, ensure stability, and allow for seamless integration of the primary packaging into a delivery device.

Characteristics of Biologic Drugs

The inherent characteristics of biologic drugs—such as their viscosity, stability, and formulation—can also significantly impact the primary packaging selection process. Biologics are often large, complex molecules, and their physical properties can present unique drug delivery and packaging compatibility challenges.

Next to aggregation and (sub)visible particle formation, viscosity is one of the most critical factors to consider in high-concentration formulations. The viscosity typically rises as the concentration of a biologic increases, especially in antibody formulations. Viscosity increase can lead to a drug being harder to expel from syringes or cartridges, resulting in higher required injection forces. Skillful formulation development, as is performed at Coriolis Pharma, can reduce the viscosities of highly concentrated drug products, but careful primary packaging selection is paramount to managing highly viscous products. For example, using dedicated needles with a higher inner diameter can increase product flow in one solution. Furthermore, it’s essential to ensure the device can handle the required injection forces without compromising the drug’s integrity or the device’s usability.

The Role of Analytical Services in Primary Package Selection

Selecting the right primary packaging goes beyond choosing materials and container sizes—it also requires comprehensive analytical testing to ensure that the packaging maintains the drug’s stability and functionality throughout its lifecycle. Coriolis Pharma’s expertise and portfolio of biopharmaceutical analytical services enable clients to make data-driven decisions by thoroughly testing packaging materials for a range of factors.

One key area of analytical testing is material compatibility testing. By evaluating the impact of the primary packaging on the critical quality attributes, this testing can derisk the whole development process and help guide the primary packaging selection.

Compatibility between the biologic drug and its primary packaging materials is paramount. The drug must not react with the packaging materials, which could cause degradation or aggregation of the active ingredient. Common packaging materials, such as glass and rubber components, plus their corresponding coatings, need to be carefully evaluated for their interaction with the biologic, and residuals from the manufacturing or leachables need to be considered.

For instance, in most syringes and cartridges, a thin layer of silicone oil is applied to the inside of the glass barrel to reduce friction and improve functionality. However, silicone oil can affect protein stability and lead to particulate formation. Tungsten contamination, often found in staked needle syringes due to the needle-affixing process, can also lead to protein aggregation, which can impact the drug’s effectiveness and cause adverse immune reactions.

Syringe and cartridge manufacturers are increasingly addressing these concerns, and many advancements are being made, including innovative silicon coating technologies and improved manufacturing processes for staked needle syringes, which reduce tungsten and other leachables within the final container.

Functionality testing is equally important. This testing evaluates the forces needed to expel the drug from the packaging, measuring parameters such as break-loose, gliding force, and expulsion time. Those parameters give insight into the ease of use and compatibility with devices. Ensuring the functionality of primary packaging is essential for maintaining drug stability and ensuring patient compliance and comfort during self-administration.

Another important topic is container-closure integrity testing, which tests whether the packaging provides an airtight seal and protects the drug from external contaminants. This guarantees that no gas, moisture, or microorganisms can enter the container, thus maintaining the drug’s sterility and efficacy.

Finally, dedicated biopharmaceutical analytical services are crucial in conducting root cause analyses when unexpected issues arise. Whether identifying causes of aggregation, assessing degradation, or revealing the identity of particulate matter, these services provide the critical insights needed to solve complex problems.

At Coriolis Pharma, the multitude of variables affecting primary packaging selection covered above are considered and assessed not only at the project start but also along the intended shelf-life of the drug by combining the testing with stability studies.

Future Trends Influencing Primary Packaging Selection

The future of primary packaging is shaped by innovations that address the evolving needs of biologics and patient-centric care:

• High-volume devices: New types of auto-injectors and on-body injection devices enable the SC delivery of larger volumes above the traditional 2 ml.
• High viscosity: New specialty needles with thinner walls and devices able to handle higher injection forces enable SC delivery of viscous solutions above the standard viscosity cutoff of 15-20 cP.
• Advanced materials: Innovations like cross-linked silicon oil coatings and ultra-low tungsten syringes enhance material compatibility and reduce stability risks.
• Customizable solutions: Tailored packaging designs are improving usability and adherence, particularly for chronic conditions requiring frequent administration.

As an independent contract research and development organization, Coriolis Pharma can help clients facilitate discussions with the multiple parties involved in developing a successful drug product, from the syringe or cartridge supplier to the contract manufacturing organization (CMO) to the device manufacturer, and guide the development based on our deep knowledge routed in formulation development.

Conclusion

Primary packaging, especially for self-administration, is more than just a container; it is a critical component of the drug product that impacts every aspect of its safety, efficacy, and patient experience. Hence, primary packaging selection and evaluation are integral parts of the drug product development process. The challenges of meeting the demand for increasing self-administration delivery systems require a meticulous approach to primary packaging selection, supported by expert analysis and innovative solutions.

Coriolis Pharma stands out as a trusted partner for clients and primary packaging and device manufacturers navigating the complexities of primary packaging selection. Our team offers:

• Formulation development expertise: Designing formulations for biologic drugs to fit specific packaging requirements, balancing stability, viscosity, and delivery needs.
• Problem-solving capabilities: Conducting root cause analyses to address unexpected challenges in drug-packaging interactions.
• End-to-end support: Assisting clients from early development through phase III clinical trials to ensure a seamless transition to commercialization.

Our science-forward approach ensures that every decision is backed by robust data and technical insights, enabling innovators to deliver safe and effective therapies to patients.