Process analytical technology (PAT) for biopharmaceutical products

Abstract

The "Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century--A Risk Based Approach" initiative announced by the FDA in August 2002 to improve and modernize pharmaceutical manufacturing facilitated adoption of process analytical technology (PAT) by the pharmaceutical industry. The potential for improved operational control and compliance resulting from continuous real-time quality assurance was highlighted as a likely benefit that would result from PAT implementation. A considerable amount of work has been done on this topic by academic and industrial contributors in the last decade. In this paper, we will start with a brief overview of evolution of PAT concepts and a review of their application in the wider pharmaceutical industry. The rest of the paper focuses on PAT applications for biotech processes with emphasis on developments in the last five years. It is our observation that while significant advances have been accomplished with regard to our ability to analyze/monitor key process and quality attributes in the biotech industry, much more needs to be done with regard to utilizing the collected data for subsequent control of the process, to achieve optimum yield and product quality. The latter is necessary to achieve the benefits that will result from PAT implementation.

Process analytical technology (PAT) for biopharmaceuticals

“…Jarka Glassey 1 , Krist V. Gernaey 2 , Christoph Clemens 3 , Torsten W. Schulz 3 , Rui Oliveira 4,5 , Gerald Striedner 6 , Carl-Fredrik Mandenius 7 goals [4,5]. In QbD the acceptable ranges of the CQAs and the CPPs are defined for the manufacturing process (Fig.…”

“…Identification of deviations from nominal batch behaviour either in the seed or production cultivations (e.g. [9]), early detection of contamination or detection of faulty sensors are all critical process decisions that have been improved using MVDA techniques [2]. However, most importantly, the PAT methodology, as defined by the FDA [1], requires effective control of CPPs affecting the CQAs.…”

“…The FDA uses the expression "to build in quality into the pharmaceutical manufacturing process", thereby implying that high product quality should ideally be created already at the design stage of the manufacturing process [1][2][3], contrary to traditional processes that are often the result of empirical or rule-of-thumb design. In addition, they also emphasize the need for improved on-line monitoring and control methods to maintain high product quality during manufacturing operations.…”

Quality by design (QbD) and process analytical technology (PAT) applications in pharmaceutical industry

“…Guidelines such as ICH Q8, ICH Q9, ICH Q10, ICH Q11 and ICH Q12 published by the International Harmonization Commission (ICH) detail the scientific and innovative design and quality perception required to ensuring consistent product quality [3]. When the literature is examined, while there are a large number of studies [4][5][6][7][8][9][10][11][12] in which QbD and Process Analytical Technology (PAT) applications are analyzed, it is obvious that conducting more research in this area is necessary as the benefits of the field are taken into consideration. The approach of designing pharmaceutical products with quality rather than testing the final product during the pharmaceutical product development process, which is difficult and costly, is a topic that attracts growing interest.…”

Multi-angle light scattering as a process analytical technology measuring real-time molecular weight for downstream process control

“…The Food and Drug Administration has encouraged the use of PAT to build quality into pharmaceutical manufacturing processes to ensure a consistent final product. 9,10 In this study, we coupled a HIC purification system with light scattering (LS) as a PAT to monitor and control effluent aggregation levels in real time. Light scattering is a common technique for the physical characterization of proteins.…”