Active pharmaceutical ingredient (API) production involving continuous processes – A process system engineering (PSE)-assisted design framework

Cervera-Padrell, Albert E.; Skovby, Tommy; Kiil, Søren; Gani, Rafiqul; Gernaey, Krist V.

doi:10.1016/j.ejpb.2012.07.001

Cited by 67 publications

(42 citation statements)

References 71 publications

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“…The novel concept of an end-to-end continuous manufacturing platform has been applied to continuous crystallization as an enabling technology for production of active pharmaceutical ingredients (APIs) (17). Continuous crystallization provides built-in flexibility for control that may lead to new approaches to product quality control.…”

Section: Innovation In Manufacturing and Asse Ssment Continuous Manufmentioning

confidence: 99%

Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference

Baker

Berlam

et al. 2015

AAPS J

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Abstract. On September 16 and 17, 2014, the Food and Drug Administration (FDA) and Product Quality Research Institute (PQRI) inaugurated their Conference on Evolving Product Quality. The Conference is conceived as an annual forum in which scientists from regulatory agencies, industry, and academia may exchange viewpoints and work together to advance pharmaceutical quality. This Conference Summary Report highlights key topics of this conference, including (1) risk-based approaches to pharmaceutical development, manufacturing, regulatory assessment, and post-approval changes; (2) FDA-proposed quality metrics for products, facilities, and quality management systems; (3) performance-based quality assessment and clinically relevant specifications; (4) recent developments and implementation of continuous manufacturing processes, question-based review, and European Medicines Agency (EMA)-FDA pilot for Quality-by-Design (QbD) applications; and (5) breakthrough therapies, biosimilars, and international harmonization, focusing on ICH M7 and Q3D guidelines. The second FDA/PQRI conference on advancing product quality is planned for October 5-7, 2015.

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Section: Innovation In Manufacturing and Asse Ssment Continuous Manufmentioning

confidence: 99%

Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference

Baker

Berlam

et al. 2015

AAPS J

View full text Add to dashboard Cite

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“…In addition to constraints of high product quality and process economics, a pharmaceutical process needs to fulfill the criteria for environmental issues. In particular, for pharmaceutical processes, the environmental sustainability evaluation must be performed during the early stage of process development [36] before the approval of the regulatory bodies as the re-approval of the process can be a very expensive process [37]. Constable et al [38] has reviewed "green" metrics proposed in literature and these metrics are used to increase the awareness of generated waste sources from the reaction and to identify opportunities for further improvement.…”

Section: Specialized Databasesmentioning

confidence: 99%

A Reaction Database for Small Molecule Pharmaceutical Processes Integrated with Process Information

et al. 2017

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This article describes the development of a reaction database with the objective to collect data for multiphase reactions involved in small molecule pharmaceutical processes with a search engine to retrieve necessary data in investigations of reaction-separation schemes, such as the role of organic solvents in reaction performance improvement. The focus of this reaction database is to provide a data rich environment with process information available to assist during the early stage synthesis of pharmaceutical products. The database is structured in terms of reaction classification of reaction types; compounds participating in the reaction; use of organic solvents and their function; information for single step and multistep reactions; target products; reaction conditions and reaction data. Information for reactor scale-up together with information for the separation and other relevant information for each reaction and reference are also available in the database. Additionally, the retrieved information obtained from the database can be evaluated in terms of sustainability using well-known "green" metrics published in the scientific literature. The application of the database is illustrated through the synthesis of ibuprofen, for which data on different reaction pathways have been retrieved from the database and compared using "green" chemistry metrics.

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“…Traditionally, the pharmaceutical industry has manufactured its products in large-scale batch processes with nonexistent or limited on-line process monitoring and control. Recently, as a result of encouragement from the regulatory authorities, the advent of globalization, and the increasing awareness of environmental impact, the pharmaceutical industry has been reconsidering the way drug products are developed and manufactured (1,2). The US Food and Drug Administration (FDA) has promoted the Quality by Design (QbD) approach to increase process understanding and improve quality and efficiency while minimizing risk (3).…”

Section: Introductionmentioning

confidence: 99%

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

et al. 2015

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ABSTRACT. The features of a drop-on-demand-based system developed for the manufacture of meltbased pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

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Active pharmaceutical ingredient (API) production involving continuous processes – A process system engineering (PSE)-assisted design framework

Cited by 67 publications

References 71 publications

Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference

Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference

A Reaction Database for Small Molecule Pharmaceutical Processes Integrated with Process Information

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

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