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Anurag S. Rathore - One of the best experts on this subject based on the ideXlab platform.

  • Process Analytical Technology implementation for protein refolding: GCSF as a case study.
    Biotechnology and bioengineering, 2019
    Co-Authors: Vishwanath Hebbi, Garima Thakur, Anurag S. Rathore
    Abstract:

    Process Analytical Technology is gaining interest in the biopharmaceutical industry as a means to enable consistency in Processing and thereby in product quality via Process control. Protein refolding is known to be significantly impacted by critical Process parameters and feed material attributes including composition and pH of the solubilisation and refolding buffers. Hence, to achieve robust Process control and product quality, these attributes and parameters need to be monitored. This paper presents an approach towards statistical Process control and monitoring of protein refolding, from buffer preparation to refold quenching, during manufacturing of therapeutic proteins from Escherichia coli based systems. The proposed approach utilises measurements of online redox potential, temperature, and pH for development of a statistical model. The model has then been integrated with LabView to permit real-time monitoring of the refolding Process. The proposed system has been demonstrated to successfully identify Process deviations and thereby enable Process control for manufacturing product of consistent quality.

  • Use of HPLC as an Enabler of Process Analytical Technology in Process Chromatography.
    Analytical chemistry, 2018
    Co-Authors: Anamika Tiwari, Nikhil Kateja, Shubham Chanana, Anurag S. Rathore
    Abstract:

    Online monitoring of product quality attributes using high resolution Analytical tools is a prerequisite for implementation of Process Analytical Technology (PAT) and thereby ensuring product quality and consistency. Online high-performance liquid chromatography (HPLC) has been established for real time monitoring of product quality attributes. However, requirement of liquid handling system capable of online sampling and fractionation and interfacing it with preparative scale chromatography appends to the cost and complexity of the design module of commercially available online HPLC. This paper proposes a cost-effective approach for using a traditional offline HPLC for online analysis using a 2 way/6 port valve to facilitate simultaneous automated sampling of product stream eluting from a Process column and fractionation. No sample dilution is required in the proposed approach. The versatility of the proposed online configuration has been verified by demonstrating its use for two of the most common separa...

  • Encyclopedia of Industrial BioTechnology - Process Analytical Technology: Strategies for Biopharmaceuticals
    Encyclopedia of Industrial Biotechnology, 2013
    Co-Authors: Anurag S. Rathore, Gautam Kapoor
    Abstract:

    In recent times, there is a growing need in the biopharmaceutical industry for improved Process understanding to enhance productivity and product quality. Process Analytical Technology (PAT) is a system for designing, analyzing and controlling manufacturing Processes based on an understanding of the engineering and scientific principles involved and identification of variables that affect product quality. It is based on the US FDA's belief that: “quality cannot be tested into products; it should be built-in or should be by design.” This article provides the reader with an overview of the evolution of this Technology, its key benefits and the challenges faced in its implementation. It then explains how PAT can be applied to a typical biopharmaceutical manufacturing Process involving upstream and downstream Processing, drug product manufacturing and chemometrics. Keywords: Process Analytical Technology (PAT); biopharmaceutical; quality by design (QbD); bioProcessing

  • Process Analytical Technology (PAT) for biopharmaceutical products: Part I. concepts and applications.
    Biotechnology and bioengineering, 2010
    Co-Authors: Erik K. Read, Kurt Brorson, J.t. Park, Rakhi B. Shah, B.s. Riley, Anurag S. Rathore
    Abstract:

    Process Analytical Technology (PAT) has been gaining momentum in the biotech community due to the potential for continuous real-time quality assurance resulting in improved operational control and compliance. In this two part series, we address PAT as it applies to Processes that produce biotech therapeutic products. In the first part, we address evolution of the underlying concepts and applications in biopharmaceutical manufacturing. We also present a literature review of applications in the areas of upstream and downstream Processing to illustrate how implementation of PAT can help realize advanced approaches to ensuring product quality in real time. In the second part, we will explore similar applications in the areas of drug product manufacturing, rapid microbiology, and chemometrics as well as evolution of PAT in biotech Processing.

Ayush Singh Rathore - One of the best experts on this subject based on the ideXlab platform.

  • Application of Process Analytical Technology for downstream purification of biotherapeutics
    Journal of Chemical Technology and Biotechnology, 2015
    Co-Authors: Ayush Singh Rathore, Gautam Kapoor
    Abstract:

    The concept of Process Analytical Technology (PAT) introduced by the US FDA has received a lot of attention lately. The use of such a scheme ensures robust Process performance over the entire life cycle of the product and consistent product quality at the end of the manufacturing Process. Successful implementation of PAT requires use of high resolution, orthogonal Analytical tools that are able to measure the critical quality attributes (CQA) of the raw materials and in-Process materials with the aim of ensuring final product quality. This article presents a review of PAT applications for monitoring commonly used downstream biotech unit operations. Focus of the review will be on recent advancements (last 5 years). Analytical tools that have been used in these approaches have also been discussed with reference to their speed of analysis, robustness and sensitivity. Also discussed is their potential to replace the traditional high performance liquid chromatography (HPLC) which continues to be the gold standard for analysis of biotech therapeutics. © 2014 Society of Chemical Industry.

  • Integrating systems analysis and control for implementing Process Analytical Technology in bioProcess development
    Journal of Chemical Technology and Biotechnology, 2015
    Co-Authors: James Gomes, Viki R. Chopda, Ayush Singh Rathore
    Abstract:

    This paper provides a perspective on the increasingly critical role that systems analysis and Process control play in bioProcess development today. This is of particular importance to the manufacturers of biotech therapeutics since the product quality is critical and depends on the Process and its control. Because a large number of Process variables and raw materials can influence the overall outcome of a bioProcess, the correct determination of the Process trajectory is often an intensive exercise. A follow-up involving design of a suitable Process control strategy for implementation of Process conditions would be logical. However, such an exercise can no longer consider each unit operation one at a time but rather requires holistic inclusion of all upstream and downstream unit operations for successfully meeting the global standards laid down by various regulatory agencies by exploring the potential of Process Analytical Technology (PAT) to achieve bigger objectives. In this perspective, the focus is on the core issues associated with Process integration and how these may influence future Process development. © 2014 Society of Chemical Industry.

  • Process Analytical Technology (PAT) for biopharmaceutical products
    Analytical and Bioanalytical Chemistry, 2010
    Co-Authors: Ayush Singh Rathore, Rahul Bhambure, V. Ghare
    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. Figure Ease of PAT implementation for some of the commonly used unit operations in biotech Processes

  • Process Analytical Technology (PAT) for biopharmaceutical products
    Analytical and Bioanalytical Chemistry, 2010
    Co-Authors: Ayush Singh Rathore, Rahul Bhambure, V. Ghare
    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.

  • Applying Process Analytical Technology to biotech unit operations
    BioPharm International, 2006
    Co-Authors: Ayush Singh Rathore, Ashutosh Sharma, David Chilin
    Abstract:

    Case studies were run to test Process Analytical Technology applications for protein refolding, diafiltration, and cation exchange chromatography. It is shown that it is feasible to design control schemes that rely on measurement of product quality attributes and thereby enable real-time decisions. Implementation of these schemes should result in consistent product quality and high operational efficiency. However, these advantages are balanced by requirements of a higher level of Process understanding for designing these schemes, and increased operational complexity during implementation. Increased consistency in product quality is likely to increase variability in step recovery, a parameter that is commonly considered an indicator of Process consistency.

Tim Kramer - One of the best experts on this subject based on the ideXlab platform.

  • tablet compression force as a Process Analytical Technology pat 100 inspection and control of tablet weight uniformity
    Journal of Pharmaceutical Sciences, 2019
    Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim Kramer
    Abstract:

    The modern rotary pharmaceutical tablet press is capable of accepting or rejecting individual tablets based on the measured compression force of the tablet. Because during steady operation, each tablet is compressed to the same thickness, a larger compression force implies a heavier tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured compression force thus becomes an important input to the overall control strategy, and variability in the compression force from one tablet to the next corresponds directly with the uniformity of dosage units. This provides an extraordinary opportunity to use the instantaneous compression force signal as a Process Analytical Technology to make product collection decisions on every individual tablet. Only 1 question requires investigation: how to set the main compression force limits to achieve the desired tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.

  • Tablet Compression Force as a Process Analytical Technology (PAT): 100% Inspection and Control of Tablet Weight Uniformity
    Journal of Pharmaceutical Sciences, 2018
    Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim Kramer
    Abstract:

    Abstract The modern rotary pharmaceutical tablet press is capable of accepting or rejecting individual tablets based on the measured compression force of the tablet. Since during steady operation, each tablet is compressed to the same thickness, a larger compression force implies a heavier tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured compression force thus becomes an important input to the overall control strategy, and variability in the compression force from one tablet to the next corresponds directly with the uniformity of dosage units (UDU). This provides an extraordinary opportunity to use the instantaneous compression force signal as a Process Analytical Technology (PAT) to make product collection decisions on every individual tablet. Only one question requires investigation: how to set the main compression force limits to achieve the desired tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.

Peter Merkel - One of the best experts on this subject based on the ideXlab platform.

  • Flow Water Proton NMR: In-Line Process Analytical Technology for Continuous Biomanufacturing
    Analytical chemistry, 2019
    Co-Authors: Marc B. Taraban, Katharine T. Briggs, Peter Merkel
    Abstract:

    Continuous manufacturing of biologics is one of the priorities of the biopharmaceutical industry. However, its widespread implementation is hampered by a lack of noninvasive/nondestructive Process Analytical Technology (PAT) systems capable of real-time in-line monitoring of product flow parameters, such as concentration and/or aggregate content. We have previously demonstrated that, under nonflow conditions, the water proton transverse relaxation rate, R2(1H2O), is sensitive to protein concentration and aggregate content in biopharmaceutical formulations. In the present work, we explored the potential of water proton NMR under flow conditions (flow-wNMR) to use R2(1H2O) as a quantitative indicator of protein concentration variations and aggregate levels in the Process flow. We show that, under flow conditions, R2(1H2O) is sensitive to rather small changes in protein concentration (

  • flow water proton nmr in line Process Analytical Technology for continuous biomanufacturing
    Analytical Chemistry, 2019
    Co-Authors: Marc B. Taraban, Katharine T. Briggs, Peter Merkel
    Abstract:

    Continuous manufacturing of biologics is one of the priorities of the biopharmaceutical industry. However, its widespread implementation is hampered by a lack of noninvasive/nondestructive Process Analytical Technology (PAT) systems capable of real-time in-line monitoring of product flow parameters, such as concentration and/or aggregate content. We have previously demonstrated that, under nonflow conditions, the water proton transverse relaxation rate, R2(1H2O), is sensitive to protein concentration and aggregate content in biopharmaceutical formulations. In the present work, we explored the potential of water proton NMR under flow conditions (flow-wNMR) to use R2(1H2O) as a quantitative indicator of protein concentration variations and aggregate levels in the Process flow. We show that, under flow conditions, R2(1H2O) is sensitive to rather small changes in protein concentration (<1 mg/mL) and is capable to detect variations in the aggregate content of <1%. Our findings suggest that flow-wNMR could be advantageously used as a real-time in-line noninvasive PAT for continuous biomanufacturing.

Leo Manley - One of the best experts on this subject based on the ideXlab platform.

  • tablet compression force as a Process Analytical Technology pat 100 inspection and control of tablet weight uniformity
    Journal of Pharmaceutical Sciences, 2019
    Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim Kramer
    Abstract:

    The modern rotary pharmaceutical tablet press is capable of accepting or rejecting individual tablets based on the measured compression force of the tablet. Because during steady operation, each tablet is compressed to the same thickness, a larger compression force implies a heavier tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured compression force thus becomes an important input to the overall control strategy, and variability in the compression force from one tablet to the next corresponds directly with the uniformity of dosage units. This provides an extraordinary opportunity to use the instantaneous compression force signal as a Process Analytical Technology to make product collection decisions on every individual tablet. Only 1 question requires investigation: how to set the main compression force limits to achieve the desired tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.

  • Tablet Compression Force as a Process Analytical Technology (PAT): 100% Inspection and Control of Tablet Weight Uniformity
    Journal of Pharmaceutical Sciences, 2018
    Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim Kramer
    Abstract:

    Abstract The modern rotary pharmaceutical tablet press is capable of accepting or rejecting individual tablets based on the measured compression force of the tablet. Since during steady operation, each tablet is compressed to the same thickness, a larger compression force implies a heavier tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured compression force thus becomes an important input to the overall control strategy, and variability in the compression force from one tablet to the next corresponds directly with the uniformity of dosage units (UDU). This provides an extraordinary opportunity to use the instantaneous compression force signal as a Process Analytical Technology (PAT) to make product collection decisions on every individual tablet. Only one question requires investigation: how to set the main compression force limits to achieve the desired tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.