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This webinar discusses drug substance manufacturing in early development and the very concept of being fast, agile and innovative.

This webinar highlights how a fully integrated development plan can bring together the needs of the drug product team and the clinical development team.

This presentation uses expert insight and case studies to explore formulation and solubility challenges and discuss the best strategies and technologies for advancing poorly soluble molecules, to deliver success.

Risk-Based Site Monitoring (RBSM) has been developed as an effective approach to overseeing clinical trials without compromising ethics, volunteer safety, data integrity, quality, timelines, and regulatory compliance. This approach is based on risk assessment, mitigation and, when possible, the removal of risks allowing the allocation of the resources in the activities where they are needed the most.

Here we describe how the integration of formulation development, compounding and GMP manufacturing activities within the FIH to POC program can streamline development and maximize potential for clinical success.

During high shear wet massing, changes in impellor torque occur as a result of changes in cohesive forces in the wet powder bed, and can be used to assess end points. However, for these formulations the change in torque was not sensitive enough for end point identification. Optimal end point for extrusion-spheronization reached just before the traditional wet granulation end point.

Gamma scintigraphy is a proven imaging technique used to visualize the in vivo performance of pharmaceutical dosage forms. Combined with pharmacokinetic (PK) analysis, the clinical outcomes provide an understanding of the impact of formulation composition, patient factors and human physiology on in vivo drug absorption. For oral solid dosage forms, technetium-99m and indium-111 are the most commonly used radioisotopes for scintigraphy studies. These radioisotopes can be directly incorporated into the formulations during manufacture or spiking into the drug product. For formulations such as multiparticulates, it would be challenging to radiolabel using these conventional methods. Therefore a specifically designed radiolabelled surrogate with similar physical properties to active multiparticulate was required.

The purpose of this investigation was to address the content uniformity challenge faced during the scale up for a low dose tablet formulation of Drug X on an accelerated development program. Experiments were performed to demonstrate optimized processing prior to clinical trial manufacturing (CTM).

To improve the existing formulation composition and manufacturing process of compound X which was designed for early phase development Process optimization activities focused on improving the flow characteristics of the granules, minimizing or eliminating segregation and increasing the manufacturing yield with the aim of achieving a robust process prior to the product registration campaign.

Compound X (Cmp-X) belongs to the class of PDE-5 inhibitors and is a BCS Class II candidate with equilibrium solubility <3 μg/mL, thus exhibiting a dissolution rate limited bioavailability. The purpose of this work is to develop an amorphous solid dispersion (ASD) by spray drying and monitor and improve the physical and chemical stability upon storage for developing a successful solid dosage formulation.

This edition of OBN’s Digital Event series is being organized in collaboration with Quotient Sciences and will highlight how a fully integrated development plan can bring together the needs of the drug product team and the clinical development team.