Oral solid dosage (OSD) forms are a mainstay for the pharmaceutical industry, providing a convenient, cost-effective solution to drug delivery. The outlook for the OSD market remains positive with estimates of growth reaching a compound annual rate of 6.4% between 2022 and 2032 (1).

Within this market, tablets account for the largest share, and the segment is forecast to continue to expand during the aforementioned analyzed period. The manufacture of tablets, although cost effective (particularly at scale), still requires specialist equipment and tools, which, if not maintained correctly, can cause defects in the finished product and ultimately harm the manufacturer’s bottom line.

Pharmaceutical Technology's May 2023 Trends in Manufacturing eBook

Felicity Thomas, European/senior editor, Pharmaceutical Technology Group

When referring to this article, please cite it as Thomas, F. Keeping Up with Tablet Tooling Maintenance. 

Pharmaceutical Technology's Trends in Manufacturing eBook 

Articles

Solid Dosage

A good understanding of tablet tooling and how to properly maintain these key parts will maximize lifespan of tools.

Keeping Up with Tablet Tooling Maintenance

To protect patient safety, drug developers and manufacturers must consider every possible route of contamination of the drug substance (DS) or drug product (DP) through all stages of production. Aseptic processes must be employed from the filling lines, containers, and stoppers to the air in the surrounding manufacturing space to maintain a sterile environment throughout fill/finish. This article explores the aseptic processing strategies biologics developers can integrate to safeguard DS and DP and examines the monitoring tactics helpful in maintaining a sterile environment.

Jeong Jin-hyeok is principal scientist in drug product at Samsung Biologics.

When referring to this article, please cite it as Jin-hyeok, J. Aseptic Processes Safeguard Biologics. 

Manufacturing

Aseptic techniques must be practiced throughout all stages of biologics production.

Aseptic Processes Safeguard Biologics

Cleanroom or classified environmental infrastructures have been designed and constructed for decades (1) and can be either on-site framed epoxy coated gypsum wall (stick-built), on-site assembled modular wall panels (modular), or off-site prefabricated cleanroom units (podular), the last of which is a relatively recent addition. All of these cleanroom material and design modalities have benefits and limitations that require careful review when making decisions on which approach to use for constructing current good manufacturing practice (CGMP) cleanroom infrastructure. Such decisions need to be made not only with the process application needs in mind, but also with the long-term perspective on future capability and capacity. This is especially important for multi-modal or multi-product processing streams and new therapies, which may not have a clearly defined process design or require process modifications along the way, and contract manufacturers, as their client base require process modalities change.

In all cases, the need for flexibility is real (2,3,4). However, flexibility must be defined, as it is often used in general terms (5). Some claim that standardization of cleanroom infrastructure designs, faster deliveries, and lower cost of goods sold, will impede or prevent flexibility. This generalization may be inaccurate, as smaller volumes require smaller process footprints, which can be reconfigured within the available standardized space (6). Such spaces may be even more flexible if units can be scaled rapidly.

To truly determine flexibility, one needs to dissect the different flexibility needs and the available solutions. Only then can an appropriate decision be made, which will not just satisfy the short-term requirements, but also show long-term benefits.

M.W. Jornitz is is Prinicipal Consultant at BioProcess Resources LLC. Sindey Blackstrom is vice-president of Business Management, Blake Williams vice-president of Operations, and Denniss Powers vice-president of Business Development, all at G-CON Manufacturing.

When referring to this article, please cite it as Jornitz, M.W. et al. The Quest for Cleanroom Flexibility. 

Cleanrooms

Contextualizing what type of flexibility is needed is paramount when considering cleanroom design.

The Quest for Cleanroom Flexibility

Pharmaceutical manufacturing equipment companies and technology providers are exploring how artificial intelligence (AI) can benefit process control systems. Two Italian companies—pharmaceutical machinery manufacturer Luperini and technology start-up Eigengran—partnered to launch AI-enabled equipment for oral solid dosage drugs that they have called Cognitive Pharma Machinery.

Luperini signed a licensing agreement to use Eigengran’s cognitive control technology in December 2022, following 18 months of testing and development. The initial work focused on high-shear wet-granulation (HSWG). In one-pot HSWG equipment, such as that made by Luperini, the entire granulation process, including the drying step, is performed within one unit. This set-up was well-suited for the initial project of developing a cognitive control system using process analytical technology (PAT) sensors to monitor the progression of the granulation process over time.

“Our technology is a key element in the application of PAT guidelines for oral drug production and will be a key step towards achieving Pharma 4.0 practice in the pharmaceutical manufacturing process,” said Marco Luperini, chief technology officer of Luperini, in an announcement of the technology (1). Luperini’s new test center in Chiesina Uzzanese, Italy houses pilot machines for evaluation to simulate conditions that may be encountered in real-world scenarios.

Jennifer Markarian is manufacturing reporter for 

When referring to this article, please cite it as Markarian, J. AI Algorithms Find Use in Pharma Equipment. 

Pharmaceutical Technology Trends in Manufacturing

Process Control

Machine learning provides real-time data for process control of high-shear wet granulation.

AI Algorithms Find Use in Pharma Equipment

The future continuous pharmaceutical manufacturing is desired to be based on modular plug-and-play concept. In this approach, mobile modules consisting of a group of unit operations need to be developed that can be easily reconfigured to assemble a scalable pharmaceutical manufacturing process for different products. It is also suitable for on-demand urgent manufacturing such as in the case of the COVID-19 pandemic. However, because of different levels of complexity, the development and adaptation of flexible and modular CM plants is still an open area of research (1-3). Therefore, a systematic framework of methods and tools are needed to develop, adapt, and evaluate the flexible modular CM plant for API manufacturing with reduced time and resources. In particular, a digital twin is critical for quick design, adaptation, optimization, scale up, and control of continuous APIs manufacturing process, allowing for virtual modeling of operations without extensive process development.

In this work, a digital twin for continuous APIs manufacturing process using modular components has been developed. This involves building a digital twin model library of the unit operations commonly used in continuous API manufacturing processes that can be easily integrated to develop the integrated digital system for a range of drug manufacturing processes. Such a toolbox will greatly facilitate the implementation of economically competitive API manufacturing processes, significantly enabling reshoring of API manufacturing activities, and will support effective “digital evaluation” of the manufacturing process by regulators. Additionally, the toolbox will greatly facilitate digital process design, digital process implementation, digital scale-up, and process optimization for API manufacturing systems.

Read this article in the Pharmaceutical Technology Trends in Manufacturing 2023 eBook

Ravendra Singh is faculty of the Department of Chemical and Biochemical Engineering at Rutgers University.

When referring to this article, please cite it as R. Singh, "Advanced Continuous Manufacturing of Drugs," 

Pharmaceutical Technology's Trends in Manufacturing

Advanced continuous manufacturing with modular components is emerging as a preferred platform to produce APIs.

Trends in Manufacturing, May 2023 eBook

Keeping Up with Tablet Tooling Maintenance

Aseptic Processes Safeguard Biologics

The Quest for Cleanroom Flexibility

AI Algorithms Find Use in Pharma Equipment

Advanced Continuous Manufacturing of Drugs