Evaluation of PAT Methods for Potential Application in Small-Scale, Multipurpose Pharmaceutical Manufacturing Platforms

Abstract

Small-scale (refrigerator-sized, 1.0 (width) × 0.7 (length) × 1.8 m (height)), multipurpose pharmaceutical manufacturing platforms (PMP) necessitate unique high demands on process analytical technologies (PAT), for instance, in in situ, real-time monitoring of liquid formulations (solution and suspension) to determine the strength prior to the release from PMPs that are not comparable to lab-scale or industrial-scale needs. Commercially available plug-and-play PATs were evaluated for their potential application in PMPs regarding versatility, flexibility, reliability, and physical size (including the control box). The results presented here indicate that single-frequency ultrasounds currently surpass commercially available plug-and-play PATs in ways such as focused beam reflectance measurements, conductivity, and turbidity as well as UV–vis, Fourier transform infrared, near-infrared, and Raman spectroscopy for the purpose of in situ, real-time concentration monitoring of aqueous and alcohol-based solutions and suspension-formulated drugs in one single PAT device, as it is preferred in PMPs to maintain a small footprint.

Performance Evaluation of a High-Precision Low-Dose Powder Feeder

“…Common to all continuous manufacturing operations is the need to create continuous powder flows ( 5 – 8 ). While feed rates of kilograms per hour can be attained using standard equipment, low feed rates in the range of grams per hour are difficult to achieve due to the intermittent nature of granular flows from small-scale screw conveyors.…”

PAT Implementation on a Mobile Continuous Pharmaceutical Manufacturing System: Real-Time Process Monitoring with In-Line FTIR and Raman Spectroscopy

“…Therefore, enabling real-time monitoring of the synthesis steps was considered a key component to the overall success of the project. In addition, selection of the analytical instruments on the PoD synthesis unit required considerations of not only the accuracy and robustness of analyzers but also the space constraints of the PoD unit 18 and the ultimate need for portability.…”

“…There has been an ongoing interest in continuous manufacturing (CM) as an alternative to traditional batch manufacturing in the pharmaceutical manufacturing sector. , This motivation lies in the potential for increased process efficiency and safety and reduced process time, waste, space requirements, and operational costs. − CM is also recognized as a promising manufacturing method for alleviating drug shortages and quality issues. , Guidance for process analytical technology (PAT) was introduced in 2004 by the Food and Drug Administration (FDA) with the aim of encouraging the pharmaceutical industry to establish advanced analytical strategies . Enabling real-time process monitoring and control technology with PAT plays a significant role in understanding manufacturing processes and ensuring product quality. − Various examples of successful PAT implementation have been reported in active pharmaceutical ingredient (API) synthesis and purification, drug product manufacturing, and biopharmaceutical manufacturing. − …”

Improved Understanding of Cefixime Trihydrate Reactive Crystallization and Process Scale-up with the Aid of PAT

“…PAT instrument studied for crystallization includes ATR-FTIR, online imaging, ultrasound, and Raman; and the work has been reviewed in some review and research articles. [16][17][18][19][20][21][22][23] In this work, on-line imaging and ATR-FTIR were used to find and define the operational envelopes leading to desired CSDs. The PAT instrument was applied during experiments to qualitatively and quantitatively characterize the crystal growth of azithromycin and polymorph transition and study the effects of several variables including the addition of water as an anti-solvent, temperature, and stirrer speed.…”