Formulation Development

Studies designed to identify suitable formulation corridors and compositions (pH, ionic strength, protein concentration, excipients, etc.) identify degradation products and develop and select stability-indicating methods. Additionally, using high-throughput formulation approaches based on the design of experiments reduces the required material and time.

Liquid, frozen or freeze-dried formulations are commonly developed for toxicological studies and can be produced under aseptic conditions.

We can transfer your formulation to our process development team or to your chosen contract manufacturing organization (CMO). This flexibility reduces costs and helps to minimize risks.

Our biologics formulation experts will help you quickly reach the clinic. We can address formulations in different primary packaging materials such as vials, prefilled syringes, or cartridges, and tackle challenging tasks like high-concentration formulations.

We will ensure your formulation is scalable and can meet the demands of late-phase development and commercial production.

Drug product formulation development is significantly impacted by the need to lyophilize the drug, as it requires a strategic approach to ensure product integrity and process efficiency. Key considerations include:

• Stability Enhancement: Removing water improves chemical and physical stability, but the formulation must also protect the drug during the freezing and drying phases. This often involves stabilizers and cryoprotectants to prevent degradation or aggregation.
• Excipients Selection: Choosing the right excipients is essential as they stabilize the active product ingredients and help maintain the structure of the lyophilized cake, ensuring consistent reconstitution and optimal drug efficacy.
• Process Compatibility: The formulation must align with the lyophilization cycle conditions —freezing, primary, and secondary drying. Adjustments to pH, buffer systems, and solute concentrations may be necessary to handle thermal and mechanical stresses during processing.
• Reconstitution Efficiency: A well-designed formulation ensures that the final product reconstitutes quickly and uniformly, preserving bioactivity and facilitating ease of administration.
• Scalability: It’s crucial that the formulation performs consistently from laboratory-scale development to full-scale production. This means the lyophilization process must be fine-tuned to meet critical quality attributes throughout scale-up.

A biopharmaceutical formulation is pivotal to its stability, as it directly influences both its chemical integrity and physical structure. Key factors include:

• Excipients and Stabilizers: Excipients help protect sensitive biomolecules by preventing aggregation and degradation, particularly for proteins and peptides.
• pH and Buffer Systems: The formulation’s pH and buffer composition are optimized to reduce the risk of denaturation and chemical degradation, ensuring that the biopharmaceutical remains active over its shelf life.
• Moisture and Lyophilization: Controlling moisture is critical for many biopharmaceuticals. Techniques like lyophilization remove water, enhancing stability by limiting hydrolytic reactions and improving long-term storage.
• Temperature Sensitivity: The formulation is designed to maintain stability across its intended temperature range, minimizing the risk of thermal degradation during storage and transport.

A biopharmaceutical’s formulation is critical in controlling degradation and aggregation to avoid compromising drug safety, efficacy, and shelf life. Some of the factors of effective biopharmaceutical formulation include:

• Excipient Selection: Stabilizers can protect proteins from degradation by stabilizing their native structure and reducing surface adsorption, which can lead to aggregation.
• pH and Buffer Composition: The formulation’s pH affects the ionization state of the protein and can influence both chemical degradation (e.g., deamidation, oxidation) and aggregation pathways. Buffers are carefully selected to minimize pH shifts during storage.
• Ionic Strength and Solvent Environment: High ionic strength can promote aggregation, while certain solvents or co-solvents may accelerate degradation. The formulation must balance these factors to preserve stability.
• Temperature and Freeze-Thaw Protection: Proper formulation includes components that protect biopharmaceuticals during temperature fluctuations and freeze-thaw cycles, common triggers for aggregation and structural degradation.
• Lyophilization Compatibility: For lyophilized drugs, the formulation must include cryo- and lyoprotectants to protect the molecule during freezing and drying, preventing stress-induced aggregation or unfolding.