Process Analytical Technique (PAT): An Integral Part of Pharmaceutical Process Automation

Analytical and Bioanalytical Chemistry, 2010

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. Figure Ease of PAT implementation for some of the commonly used unit operations in biotech processes

International journal of pharmaceutics, 2018

The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial least squares (PLS) regression. The authors understand that this is the first study where the continuous manufacturing (CM) equipment was used as a gravimetric reference method for the calibration model. A principal component analysis (PCA) model was also developed to identify the powder blend, and determine whether it was similar to the calibration blends. An air diagnostic test was developed to assure that powder was present within the interface when the NIR spectra were obtained. The air diagnostic test as well the PCA and PLS calibration model were integrated into an industrial software platform that collects the real time NIR spectra and applies the calibration models. The PCA test succes...

Journal of Chemometrics, 2012

The role of chemometrics in process analytical technology (PAT) solutions development is presented in the review on the basis of publications from 1993 to 2011. Main areas of application, stages of implementation, instruments, and chemometric methods used for the PAT implementations are reviewed. Generally speaking, PAT is considered to be an approach applicable not only in pharmaceutical industry but also in any production area such as food industry and biotechnology. PAT is claimed to be a new flexible manufacturing concept that accounts for variability and adapts the process to fit it.

rjptonline.org

The demand for better healthcare products is ever increasing. The technologies which were the best for producing the quality products few years back is no more so. The advent of new tools and technologies has given an opportunity for all the pharmaceutical producers to improve upon their quality standards. Process Analytical Technology is one among them. The application of Process Analytical Technology in pharmaceutical production checks the quality of the raw material attributes both physically and chemically, that too at-line, in-line or on-line, which was not possible earlier, thereby decreasing the chances of contamination and cross contamination. It also saves a huge amount of time and money required for sampling and analysis of the products. Overall Process Analytical Technology paves a way for producing a quality product thus satisfying the customer needs and creating a good brand image for the organization. In this article, Process Analytical Technology has been introduced briefly and its different tools have been discussed to illustrate how application of this technology ensures quality of the pharmaceutical products.

Archives of Applied Science Research, 2015

The requirement for enhancing healthcare products is eternally increasing. In this regard, the requisite for monitoring all the physical and chemical attributes during the manufacturing of the health care products with a lesser time is truly essential. A new tool, Process analytical technology (PAT) is used to monitor and control critical process parameters in materials and in-process products to maintain the critical quality attributes and build quality into the product. Process Analytical Technology checks the quality of the materials on-line, which saves a huge amount of time and facilitates rapid testing through direct sampling without any destruction of sample. However, to successfully adapt PAT tools into pharmaceutical and biopharmaceutical environment, thorough understanding of the process is needed along with mathematical and statistical tools to analyze large multidimensional spectral data generated by PAT tools. Chemometrics is a chemical discipline which incorporates bot...

Process analytical technology (PAT) involves the use of different technologies and tools to build quality into the products. Effective PAT implementation comprise of science-based understanding of the physical, chemical and mechanical properties of all elements of the proposed drug product. The overall PAT venture is promising for delivering an integrated systems approach for quality design, process analysis, understanding and control, continuous improvement, knowledge and risk-based management. The incorporation of early PAT devices, increase process efficiency and safety by acting on data in real time and by eliminating sampling. PAT applications, increase detailed knowledge of processes, leading to increased robustness and greater processing opportunities. Modern developments in analytical technologies provide chemical and analytical insights for all types of chemical reactions and process monitoring such as drying, distillations, crystallizations, hydrogenations, and others.

International Journal of Applied Pharmaceutics, 2024

FDA initiated the PAT technology framework in the year of 2004 with the guidelines of "A framework of innovative pharmaceutic al development, manufacturing and quality assurance. With that, the International Council for Harmonisation has also initiated continuous process verification to overcome the limitations of traditional methods and improve the understanding of the process and quality of the product throughout the product lifecycle. Since the year of implementation, the advancement of analytical and chemometric tools has evolved to deliver consistent quality products by understanding their process and product performance. However, the pharmaceutical industry was lacking in this technicality and implementation of highly regulated specifications. To this respect, we have stated some of the PAT tools, including NIR, Raman and Terahertz spectroscopy, as they will transfer to the futuristic prospects of analyzing the drug product with non-destructive, improved process understanding, real-time monitoring, and enhanced data integrity. This review article emphasizes the importance of PAT technology with different monitoring processes with their historical background and regulatory framework. Special attention was given to strategies, challenges, o pportunities, and the compatibility of PAT tools with data fusion. Further, this will give a high-priority disciplinary scientific topic to Pharma 4.0.

TrAC Trends in Analytical Chemistry, 2015

Currently, pharmaceutical production is making the switch from batch processing towards continuous processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the advantages of continuous processing, so the critical quality attributes of continuously produced pharmaceuticals need to be monitored in real time. In 2004, the US Food and Drug Administration launched the process analytical technology (PAT) concept to stimulate the pharmaceutical industry to change from off-line to real-time quality testing. This review explores the implementation of PAT tools within continuous pharmaceutical processes (i.e., blending, spray drying, roller compaction, twin-screw granulation and compression), focusing on both opportunities and challenges.

Chemometrics and Intelligent Laboratory Systems, 2004

The production process of an active pharmaceutical ingredient (API) by fermentation in an industrial environment was analysed using process analytical technologies.The Food and Drug Administration's (FDA) process analytical technology (PAT) initiative is intended to be a collaborative effort with industry to promote the integration of new manufacturing technologies into pharmaceutical production [FDA. 2003 bPAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance (Draft Guideline).Q http://www.fda.gov/cder/OPS/ PAT.htm]. Within the PAT framework the aim is to design, develop and operate processes consistently to ensure a predefined quality at the end of the manufacturing process. Several case-studies are discussed in which combining chemometrics methods with NIR spectra from samples in different process stages leads to increased process understanding and process control of an API production process. The ab-initio prediction of the expected final titter of an antibiotic fermentation was obtained with raw materials and inoculum quality quantification. NIR reflectance spectroscopy was applied to monitor at-line different quality variables for process samples taken from the fermentation stage of the whole process. Finally, the at-line use of NIR transmittance spectroscopy in one of the API downstream purification steps is described. In this paper the use of PAT as a tool to operate an important shift in quality control efforts is illustrated, showing that quality should not be tested only on final products but in-process to obtain increased quality assurance of final products. D

2006

Process analytical technologies have been applied to manufacturing processes (pulp and paper, chemical and petroleum) for decades. Recently, the US Food and Drug Administration (FDA) has, however, redefined the phrase and implemented it into an initiative focusing on improving several aspects of the pharmaceutical industry. The European Agency for the Evaluation of Medicinal Products (EMEA), has also been active and formed a PAT team in 2003. The PAT initiative was initially intended for traditional pharmaceutical manufacturers, but the FDA's PAT guidance now clearly states that it applies to all manufacturers of human and veterinary drug products, as well as biologics regulated by the FDA's Center for Drug Evaluation and Research (CDER) and the Center for Veterinary Medicine (CVM). Basically, PAT involves a fundamental shift from testing the quality of the finished drug product, to building quality into products by testing at several intermediate steps. It specifically requires that quantifiable, causal, and predictive relationships be established amongst raw materials, the manufacturing process, and final product quality. It is believed that PAT may not bring dramatic changes overnight, but years from now, it may be seen as an initiative that helped foster a period of innovation, efficiency, and expansion for the biopharmaceutical industry. In this report, the impact and potential effects of PAT on the biotechnological production of pharmaceuticals is assessed. Hence, we define BioPAT as process analytical technologies applied throughout development, scale-up and commercial scale bioprocess-based production of drug substances. In this report, we will focus on what PAT means in practice for the biotechnological manufacture of pharmaceuticals. Besides a regulatory examination, the monitoring methods and technologies available are thoroughly surveyed. These facts are then reflected against the needs for monitoring in bioprocess-based pharmaceutical production.

Engineering in Life Sciences, 2013

The process analytical technology (PAT) initiative is now 10 years old. This has resulted in the development of many tools and software packages dedicated to PAT application on pharmaceutical processes. However, most applications are restricted to small molecule drugs, mainly for the relatively simple process steps like drying or tableting where only a limited number of parameters need to be controlled. A big challenge for PAT still lies in applications for biopharmaceuticals and then especially in the cultivation process step, where the quality of a biopharmaceutical product is largely determined. This review gives an overview of the currently available tools for monitoring and controlling the biopharmaceutical cultivation step and of the main challenges for the most common cell platforms (i.e. Escherichia coli, yeast, and mammalian cells) used in biopharmaceutical manufacturing. The real challenge is to understand how intracellular mechanisms (from synthesis to excretion) influence the quality of biopharmaceuticals and how these mechanisms can be monitored and controlled to yield the desired end product quality. Modern "omics" tools and advanced process analyzers have opened up the way for PAT applications for the biopharmaceutical cultivation process step.

Chemometrics and Intelligent Laboratory Systems, 2006

Checking that a process is doing what it is supposed to is of critical importance in manufacturing, economics, environmental monitoring, patient monitoring, and more. Given sufficient and adequate analytical and process measurements made during the history of the well functioning process, a multivariate model of the process variation around a multivariate dynamic trajectory will, in principle, form a good basis for this checking. Such systems are often labeled process monitoring, real-time quality control (RTQC), PAT level 4, and advanced process control/fault detection and classification (APC/FDC). Here PAT stands for process analytical technology indicating the reliance on adequate and multiple data for this checking. In practice, there are many difficulties in making an RTQC/PAT-4 system work well. Starting from an industrial example, the problems of constructing and implementing a well working checking system are discussed in relation to its different partsanalytical and process data, chemometrical and other methods for their modeling and analysis, and various forms of data management to handle the data flow and synchronization, as well as storage and retrieval. The display and interpretability of diagnostics and results are emphasized.

The pharmaceutical industry is in rapid transition from a supply-driven market to a demand and servicedriven market where manufacturing efficiency and responsiveness will play a critical role in future success. To overcome this there is growing enthusiasm in the industry for the many potential gains offered by Process Analytical Technology, a new FDA initiative that aims to foster improvements in manufacturing efficiency and quality analysis. Pharma Industry is facing growing demands for increased productivity and reduced manufacturing costs and also has to meet the evolving need for higher quality standards and higher drug expectations The regulatory area appears to be rapidly evolving, with PAT initiative to be the first major change in the GMP's in over 25 years that is based on increased scientific understanding and less on an empirical based approach. PAT is important because, if it is successfully introduced, it will pioneer a new concept of regulation of quality in the 21 st century.The PAT Approach is based on steps, strategy, cost, benefits and rules during implementation of pat.

Journal of Pharmaceutical and Biomedical Analysis, 2019

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