(203m) Continuous Manufacturing of Oral Disintegrating Films: A Quality By Design Approach

Cruz, C. N., U.S. Food and Drug Administration
Mazumder, S., Office of Testing and Research, U.S. Food and Drug Administration
Pavurala, N., Office of Testing and Research, U.S. Food and Drug Administration
Xu, X., Office of Testing and Research, U.S. Food and Drug Administration
O'Connor, T., U.S. Food and Drug Administration
Muhammad, A., U.S. Food and Drug Administration
Yazdanpanah, N., U.S. Food and Drug Administration
Taylor, C., U.S. Food and Drug Administration
The ICH guidelines and FDA guidances have encouraged pharmaceutical industries to implement risk based (ICH Q9), systematic and science–based approaches (ICH Q8 (R2) and ICH Q11), a robust pharmaceutical quality system (ICH Q10) and introduce Quality by Design (QbD) concepts, emphasizing science and risk-based approaches to assure product quality. Innovative continuous manufacturing (CM) technologies have a great potential to improve control over quality, reduce costs, enhance process safety, and significantly reduce the timelines currently involved across the medicines’ supply chain. When compared to traditional batch manufacturing, continuous manufacturing also has enhanced ability to control the process and product quality through knowledge of residence times and the implementation of process analytical technology (PAT) tools. The objective of this work is to understand the relationships between product and process variables and critical quality attributes (CQAs) of ondansetron (a model drug compound) to support development and review of control strategies for continuous manufacturing of ODFs. This can aid in the understanding of common failure modes that provide the foundation for systematic risk assessment of continuous film processing.

The ODFs of ondansetron were prepared in-house using the solvent casting method in a continuous tape caster. These films were characterized in-line, at-line or off-line for drug assay, content uniformity, disintegration, dissolution, morphology, surface roughness, wettability, thickness, % moisture uptake, % moisture content, mechanical properties.

Principles of QbD along with appropriate design of experiments (DoE) were used to obtain a comprehensive understanding about the effect of critical material attributes (CMA’s) such as % w/w of plasticizer, surfactant and critical process parameters (CPP’s) such as mixing speed, coat thickness, air flowrate and drying temperature on the quality and performance of ondansetron ODF. Suitable Design of Experiments (DoE) was used to screen and optimize critical parameters that impact the product quality of ODFs. Data analysis using ANOVA and multifactor analysis was performed in elucidating interactions between different variables, rank order the various CMA’s and CPP’s, and help provide a predictive model for the process. A design space was established and verified by performing a failure mode analysis.