How to Avoid Losing Time in Development when Bridging from First-in-Human Dosage Form to Robust and Scalable Phase II Drug Products
As a new molecule progresses through the development process, the way it is formulated as the “drug product” or “dosage form” will change in order for it to successfully achieve key clinical milestones. In early development, the first-in-human (FIH) clinical trial is often a single-center study and typically involves dosing a small number of healthy subjects over a short duration of days or weeks. In this study, the drug is administered in increasing doses and as such, a “fit-for-phase” drug product with high dose flexibility, like a simple solution, suspension or powder-in-capsule, is often used. This type of drug product can sometimes be prepared on-site, at a small scale and with limited stability studies and analytical release testing. Simple pharmacy preparations may be sufficient for FIH clinical studies, but when moving beyond Phase I into later stages of clinical development like Phase II, such products are likely to be unsuitable for patient convenience and compliance and the simple manufacturing processes not scalable to meet the larger batch sizes required for Phase II trials.
The subsequent Phase II & III patient trials will involve a much larger number of patients, take place at multiple clinical sites, often in different countries and will extend over a longer period of time. To support these trials it is likely that the development team will need to bridge to an optimized drug product, such as a solid oral dosage form like a tablet, to ensure improved patient compliance and better suitability for shipping globally. Another thing to keep in mind is that the product batch sizes manufactured to support Phase II & III trials will need to increase in order to support the increased number of patients. If the molecule is then successful in pivotal clinical studies, the batch sizes will be further increased to cover the demand for a commercially approved product.
The requirement for different product formats at each stage of development can often result in costly delays and budget overruns when it comes to product optimization and scaling up. Sometimes such CMC delays can be prevented by carefully planning and integrating development activities and technology considerations in the formulation design process. However, in order to improve R&D productivity and bring new molecules to market as quickly as possible, drug companies are actively seeking new ways of streamlining drug development using alternative outsourcing models. One such approach is to focus on smarter R&D by adopting a highly integrated model, like Quotient Sciences’ Translational Pharmaceutics® platform, in which a single outsourcing partner coordinates and adapts the drug product manufacturing requirements (“make”) with the specific needs of the clinical development plan (“test”), creating significant time efficiencies and cost savings.
In a recent webinar, Druggability Technologies presented a case study which utilized Quotient’s integrated approach to advance the development of DRGT-46, a novel, fast-acting formulation of celecoxib. The case study gives examples of how clinical data can be used to drive formulation selection in “real-time” and efficiently bridging from a Phase I drug product to a dosage form suitable for patients in late stage clinical trials. The program demonstrated how Quotient’s tight integration of formulation and manufacturing activities across a global site network has enabled DRGT to execute an efficient development plan with a single outsourcing partner and, most importantly, reduce the time from early development by having a commercial ready product.
When you are looking for a partner who can help formulate and develop your drug product from first-in-human through to proof-of-concept and beyond, rely on Quotient Sciences. With a proven track record that spans more than 30 years and a global drug development and manufacturing footprint, we will support you in accelerating a successful outcome for your program.
Read the DRGT-46 case study detailing the project using our integrated approach, Translational Pharmaceutics®.