Analytical Validation

09 Jun 2023

Guideline establishes the requirements for validationg analytical methods, ensuring consistency in the routeine measurements of pharmaceutical products and their intermediates.

Advanced methodologies for cocrystal synthesis

09 Jun 2023 | Contributor(s): Douroumis, D, Ross, SA, Nokhodchi, A

Pharmaceutical cocrystals are multicomponent systems composed of two or more molecules and held together by H-bonding. Currently, cocrystals provide exciting opportunities in the pharmaceutical industry for the development and manufacturing of new medicines by improving poor physical properties...

Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press

09 Jun 2023 | Contributor(s): Haas, Nicholas Townsend, Ierapetritou, Marianthi, Singh, Ravendra

In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical tablets can be produced...

Advanced Pharmaceutical Manufacturing: A Functional Definition

09 Jun 2023 | Contributor(s): Romañach, Rodolfo J., Stelzer, Torsten, Sanchez, Eric, Muzzio, Fernando

The term “Advanced Pharmaceutical Manufacturing” (APM) has become an ubiquitous buzzword with deep potential policy implications. There is a real danger that APM will be seen as a general panacea for solving economic woes and drug shortages, devoiding it from specific meaning, and depriving the...

Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow

09 Jun 2023 | Contributor(s): Sagmeister, Peter, Lebl, René, Castillo, Ismael, Rehrl, Jakob, Kruisz, Julia, Sipek, Martin, Horn, Martin, Sacher, Stephan, Cantillo, David, Williams, Jason D, Kappe, Oliver

In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and...

Advances in Continuous Active Pharmaceutical Ingredient (API) Manufacturing: Real-time Monitoring Using Multivariate Tools

09 Jun 2023 | Contributor(s): Dumarey, Melanie, Hermanto, Martin, Airiau, Christian, Shapland, Peter, Robinson, Hannah, Hamilton, Peter, Berry, Malcom

Purpose: The implementation of continuous processing technologies for pharmaceutical manufacturing has increased due to its potential to enhance supply chain flexibility, reduce the footprint of the manufacturing facility, and deliver more consistent quality. Additionally, it facilitates...

Advances in Twin-Screw Granulation

09 Jun 2023 | Contributor(s): Vanhoorne, Valerie, Kumar, Ashish

Twin-screw granulation (TSG) is an emerging process technology that allows both wet and dry granulation of powders with a wide range of properties. This technology is of particular interest to the pharmaceutical industry, which is currently aiming to shift from batch to continuous mode...

Advances in Twin-Screw Granulation Processing

09 Jun 2023 | Contributor(s): Nandi, Uttom, Trivedi, Vivek, Ross, Steven A., Douroumis, Dennis

Twin-screw granulation (TSG) is a pharmaceutical process that has gained increased interest from the pharmaceutical industry for its potential for the development of oral dosage forms. The technology has evolved rapidly due to the flexibility of the equipment design, the selection of the process...

Aerobic oxidations in flow: opportunities for the fine chemicals and pharmaceuticals industries

09 Jun 2023 | Contributor(s): Gavriilidis, A, Constantinou, AHellgardt, K, Hii, KK, Hutchings, GJ, Brett, GL, Kuhn, S, Marsden, SP

Molecular oxygen is without doubt the greenest oxidant for redox reactions, yet aerobic oxidation is one of the most challenging to perform with good chemoselectivity, particularly on an industrial scale. This collaborative review (between teams of chemists and chemical engineers) describes the...

An agile and robust in-line NIR potency deviation detection method for monitoring and control of a continuous direct compression process

09 Jun 2023 | Contributor(s): Alam, Md Anik, Liu, Yang Angela

Near Infrared (NIR) method for blend potency estimation has been commonly used as an essential tool for process monitoring and control in continuous manufacturing of solid oral dosage forms. Robustness has been the main challenge for successful application of an NIR method, which often results in...

An automated modular assembly line for drugs in a miniaturized plant

09 Jun 2023 | Contributor(s): Hu, Chuntian, Testa, Christopher, Wu, Wei, Shvedova, Khrystyna, Shen, Dongying, Sayin, Ridade, . Halkude, Bhakti, Casati, Federica, Hermant, Paul, Ramnath, Anjana, Born, Stephen, Takizawa, Bayan, O'Connor, Thomas, Yang, Xiaochuan, Ramanujamd, Sukumar, Mascia, Salvatore

We report here a fully automated, end-to-end, integrated continuous manufacturing process for a small-molecule generic medication with built-in quality assurance. The entire process fits into a box of 30.7 m2 modular footprint and a total residence time of less than 30 h, with a throughput up to...

An engineering study on the enhanced control and operation of continuous manufacturing of pharmaceutical tablets via roller compaction

09 Jun 2023 | Contributor(s): R Singh, M Ierapetritou, R Ramachandran

A novel manufacturing strategy based on continuous processing integrated with online monitoring tools coupled with efficient automatic feedback control system is highly desired for efficient Quality by Design (QbD) based manufacturing ofthe next generation of pharmaceutical products with optimal...

Achieving continuous manufacturing in lyophilization: Technologies and approaches

09 Jun 2023 | Contributor(s): Pisano, Roberto, Arsiccio, Andrea, Capozzi, Luigi C., Trout, Bernhardt L.

This paper provides an organic overview of the most interesting continuous freeze-drying concepts that have been proposed over the years. Attention has mainly been focused on the field of pharmaceuticals, but some background has also been given on the food industry. This work aims at providing a...

Achieving Continuous Manufacturing: Technologies and Approaches for Synthesis, Workup, and Isolation of Drug Substance May 20-21, 2014 Continuous Manufacturing Symposium

09 Jun 2023 | Contributor(s): Baxendale, IR, Braatz, RDHodnett, BK, Jensen, KF, Johnson, MD, Sharratt, P, Sherlock, JP, Florence, AJ

This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for...

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

09 Jun 2023 | Contributor(s): Cervera-Padrell, AE, Skovby, TKiil, S, Gani, R, Gernaey, KV

A systematic framework is proposed for the design of continuous pharmaceutical manufacturing processes. Specifically, the design framework focuses on organic chemistry based, active pharmaceutical ingredient (API) synthetic processes, but could potentially be extended to biocatalytic and...

Activities related to human medicines in Romania: Legal environmental protection issues

09 Jun 2023 | Contributor(s): Toma, A, Crisan, O

Current environmental Research Article focuses extensively on pharmaceutical waste, demonstrating the contamination caused by active pharmaceutical ingredients. Regulations and programs to evaluate, prevent, and reduce environmental risks linked to human medicines are currently being developed in...

Additive Layer Manufacturing of Catalytic Static Mixers for Continuous Flow Reactors

09 Jun 2023 | Contributor(s): Hornung, CH, Singh, S, Saubern, S

With a design guided by computational fluid dynamics (CFD), additively manufactured from base metals and coated with metal catalysts using cold spray technology or electroplating, catalytic static mixers are used to replace fixed bed columns in continuous flow reactors. We have shown their...

Adequacy and Verifiability of Pharmaceutical Mixtures and Dose Units by Variographic Analysis (Theory of Sampling) - A Call for a Regulatory Paradigm Shift

09 Jun 2023 | Contributor(s): Esbensen, Kim H, Román-Ospino, Andrés D., Sanchez, Adriluz, Romañach, Rodolfo J.

In spite of intense efforts in the last 20 years, the current state of affairs regarding evaluation of adequacy of pharmaceutical mixing is at an impressive standstill, characterized by two draft guidances, one withdrawn, and the other never approved. We here analyze the regulatory, scientific...

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Zhang, P, Weeranoppanant, NThomas, DA, Tahara, K, Stelzer, T, Russell, MG, O'Mahony, M, Myerson, AS, Lin, HK, Kelly, LP, Jensen, KF, Jamison, TF, Dai, CH, Cui, YQ, Briggs, N, Beingessner, RL, Adamo, A

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on...

Advanced control of a continuous oscillatory flow crystalliser

09 Jun 2023 | Contributor(s): Tahir, F, Krzemieniewska-Nandwani, KMack, J, Lovett, D, Siddique, H, Mabbott, F, Raval, V, Houson, I, Florence, A

This paper presents the application and challenges of achieving Model Predictive Control (MPC) on two continuous oscillatory baffled crystallisation reactors, delivering precise product quality control in the face of raw material fluctuations. A key advantage of MPC is that it effectively deals...

Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes

09 Jun 2023 | Contributor(s): Singh, Ravendra, Velazquez, Carlos Sahay, Abhishek Karry, Krizia M Muzzio, Fernando J Ierapetritou, Marianthi G, Ramachandran, Rohit

A novel manufacturing strategy based on continuous processing, integrated with online/inline monitoring tools, coupled with an advanced automatic feedback control system is highly desired for efficient Quality by Design (QbD)-based manufacturing of the next generation of pharmaceutical products...

Advanced Manufacturing and Process Analytical Technology - for Competitiveness and Resilience in Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Alvarado-Hernández, Bárbara, Fontalvo-Lascano, María A., Valetín-Román, Nashaly, Méndez- Román, Rafael, Méndez Piñero, Mayra, De Hoyos Ruperto, Moraima., Romañach, Rodolfo

A systematic framework to monitor mulling processes using Near Infrared spectroscopy

09 Jun 2023 | Contributor(s): Wu, Suyang, Panikar, Savitha S Singh, Ravendra Zhang, Jun Glasser, Benjamin, Ramachandran, Rohit

The optimal design of sensor location and setup is essential to ensure the accuracy and precision of in-line process monitoring of water/moisture content. This manuscript presents a systematic framework of using Near Infrared (NIR) spectroscopy to monitor moisture content in an alumina mulling...

A systematic reactor design approach for the synthesis of active pharmaceutical ingredients

09 Jun 2023 | Contributor(s): Emenike, VN, Schenkendorf, R, Krewer, U

Today's highly competitive pharmaceutical industry is in dire need of an accelerated transition from the drug development phase to the drug production phase. At the heart of this transition are chemical reactors that facilitate the synthesis of active pharmaceutical ingredients (APIs) and whose...

A systematic study of the impact of changes of roller compactor equipment on granule and tablet properties

09 Jun 2023 | Contributor(s): Haeffler, Gunnar, Schmidt, Leonard, Lakio, Satu, Reynolds, Gavin, Odman, Jonas, Tajarobi, Pirjo

Typical industrial development of roller compaction processes include changes in scale from laboratory to pilot and then further to production scale and also changes in equipment design due to equipment availability in different manufacturing facilities. Transfer and scale-up of roller compaction...