Continuous manufacturing for biopharmaceutical drugs offers the potential for similar advantages to those that can be obtained by continuous processing of small-molecule drugs, including higher efficiency and flexibility of scale. At Sweden’s AdBIOPRO (the Competence Centre for Advanced BioProduction by Continuous Processing), researchers from Lund University and KTH Royal Institute of Technology aim to advance understanding of continuous bioprocessing to support industry efforts.

To this end, AdBIOPRO researchers conducted a scale-up project at the Testa Center in Uppsala, Sweden, which is a pilot-scale test center that is an initiative between the Swedish government and life sciences company Cytiva. The group demonstrated that it is possible to run a large-scale, automated continuous bioprocess in which a cell culture operated in perfusion mode directly and automatically connects to a continuous purification process, says Veronique Chotteau, professor at KTH Royal Institute of Technology and head of AdBIOPRO. 

 spoke with Chotteau about the group’s proof-of-concept work and the key components that are needed to run a fully continuous bioprocess that connects both upstream and downstream processing in one workflow.

Read this article in the Trends in Manufacturing ebook. 

Jennifer Markarian was previously manufacturing editor and is currently manufacturing reporter for 

When referring to this article, please cite it as J. Markarian, " Demonstrating a Fully Continuous Bioprocess," 

Pharmaceutical Technology's Trends in Manufacturing

Articles

Manufacturing

Flexible and efficient methods are needed for biopharmaceutical manufacturing. 

Demonstrating a Fully Continuous Bioprocess

Alternative dosage forms are helping the pharmaceutical industry tackle some of the biggest challenges associated with efficacy and patient adherence. For example, oral films that help administer treatments to pediatric and geriatric patients, and wearable injectors that enable the self-administering of high-volume treatments. Amid these innovations, it’s easy to overlook the humble tablets and capsules that have been used for generations and continue to be the most popular course of treatment around the world. The global capsule market is expected to grow at a compound annual growth rate (CAGR) of 8.1% from 2021 to 2030 (1). This amounts to approximately 700 billion units every year around the world, according to ACG data (2).

But capsules are more than the familiar favorite. Recent developments are taking oral solid dosage (OSD) solutions to new heights. Now more than ever, innovation is fueled by the need to differentiate and to deliver sustainable, advanced products in the crowded pharmaceutical market. Pharmaceutical manufacturers must also navigate evolving delivery formats, the economy of scale, complex regulatory landscapes, increasingly stressed supply chains, and digitalization, all while maintaining the highest quality standards. Therefore, it’s crucial to take steps to meet these growing challenges using the latest advanced manufacturing technologies.

Empty Capsules Market by Product, Raw Material, Therapeutic Application and End User: Global Opportunity Analysis and Industry Forecast, 2021-2030 

2. WHO, “1 in 10 Medical Products in Developing Countries is Substandard or Falsified,” (November 2017).

Laxman Shetty is the vice president, operations; Jnanadeva Bhat is the vice president, formulation R&D (pharma and nutra); and Anita Solanki is the lead for whitepapers and publications, formulation R&D (pharma and nutra), all for ACG.

When referring to this article, please cite it as L. Shetty, J. Bhat, and A. Solanki, "Manufacturing OSD Forms: Key Trends Shaping the Industry," 

Pharmaceutical Technology's Trends in Manufacturing 

The latest manufacturing technologies are essential for helping pharmaceutical formulators meet up-and-coming trends in OSD treatments. 

Manufacturing OSD Forms: Key Trends Shaping the Industry

With millions of tablets coming off production lines daily, it is no surprise that tooling can be affected. Consistent compaction of granules into a quality solid dose form is challenging enough for manufacturers without the added concern of the tooling not being up to the job.

The condition of punches and dies will have a substantial impact on productivity, so it is crucial that all tablet tooling is optimized through simple maintenance procedures to enhance performance and improve longevity.

Pharmaceutical Technology's May 2022 Trends in Manufacturing eBook

Andy Dumelow is head of Technical Sales at I Holland.

When referring to this article, please cite it as A. Dumelow, “Don’t Gamble on Tablet Tooling Maintenance,” 

Pharmaceutical Technology's Trends in Manufacturing eBook 

Solid Dosage

By following some fundamental steps, manufacturers can optimize their tablet tooling maintenance and resulting productivity.

Don’t Gamble on Tablet Tooling Maintenance

The evolution of technologies on the bioprocessing front is enabling an ability to perform continuous processing for biologic production. Although successes have been shown at small scale, challenges arise when translating continuous processes to large-scale good manufacturing practice (GMP) level. With the help of technological advances and innovative thinking, however, the potential to implement GMP-scale continuous bioprocessing is getting closer to reality. This article looks at real-world experiences of some companies that tested out the implementation of continuous manufacturing systems for GMP-scale biologics manufacture. 

Feliza Mirasol is the science editor for 

When referring to this article, please cite it as F. Mirasol, “Implementing Continuous Bioprocessing: From Theory to Practice," 

The struggle to implement continuous biomanufacturing at GMP level is slowly advancing.

Implementing Continuous Bioprocessing: From Theory to Practice

Prior to the COVID-19 pandemic, the bio/pharma manufacturing industry had been relatively slow to embrace the ongoing digital revolution. But the pandemic forced the life sciences industry and drug developers to rethink their hesitation toward digitization to quickly produce and distribute new vaccines under unprecedented conditions. Now, technology is being used as a solution to improve efficiency and sustainability in life sciences manufacturing. Those who have led the way are said to be creating the “lighthouse effect.” Just as actual lighthouses help sailors navigate dangerous waters, lighthouse companies serve as guiding lights for charting the course of an entire industry. For the life sciences manufacturing industry, becoming one of these luminaries relies on a mix of advanced technical capabilities and coming up with innovative applications for the technology. In the age of Big Data, artificial intelligence (AI) and digitization will play lead roles in achieving lighthouse effects.

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1. World Economic Forum and McKinsey & Company, “Global Lighthouse Network: Reimagining Operations for Growth,” Whitepaper, 2021.

2. C. Schmidt, “Machine Learning Poised to Accelerate Drug Discovery,” Novartis, May 7, 2018

When referring to this article, please cite it as G. Dusi, “The Lighthouse Effect: Using Technology to Improve Life Sciences Manufacturing,” 

Pharmaceutical Technology Trends in Manufacturing

Lighthouse manufacturing techniques utilize technology and automation to
streamline production.

The Lighthouse Effect: Using Technology to Improve Life Sciences Manufacturing

Lyophilization remains an integral step in the manufacturing process for certain biotherapeutics, as was demonstrated with the COVID-19 vaccines. Lyophilization is also important in traditional biologic manufacturing and for emerging therapies. However, there remains inherent risk in subjecting these biomolecules through successive freeze-thaw cycles, which call for best-practice procedures to ensure that product viability and stability are maintained during the lyophilization process. Furthermore, questions have arisen about the long-term sustainability of current lyophilization techniques as the development of new biologic and emerging therapy drug candidates continues to grow.

1. EC, “EU Legislation to Control F-gases,” ec.europa.eu, accessedJan. 14, 2022.

When referring to this article, please cite it as F. Mirasol, “Plan Early: Optimizing Stability During Lyophilization,” 

Biologics

The need for sustainability and early considerations of a lyophilization strategy grow more pertinent on the back of growing biologics volume.

Plan Early: Optimizing Stability During Lyophilization

A treatment that has been top-of-mind in recent years is cell and gene therapies (CGTs). Many companies and organizations investigate the potential of this type of treatment to address unmet medical needs. While significant headway has been made, CGTs are in their infancy. But with the potential to cure diseases, CGTs could change the future of treatments for certain conditions.

“[CGTs] offer for the first time the possibility to offer truly disease-modifying treatments, providing options for conditions considered intractable or where the current standard of care is insufficient,” says Bayer AG company sources.

1. S. Fried et al., “Patients With Out of Specification Tisagenlecleucel Can Be Salvaged With Point-of-Care CART-T Cells: An Observational Intention-to-Treat Single-Center Analysis,” presentation at 2021 European Hematology Association Virtual Conference, EHA (Virtual, Aug. 15, 2021).

2. Stasiak, Andrzej. “Gene therapy,” EMBO Reports, March 5, 2001.

3. FDA, “FDA Approves Novel Gene Therapy to Treat Patients with a Rare Form of Inherited Vision Loss,” FDA.gov, Press Release, Dec. 18, 2017.

When referring to this article, please cite it as M. Rivers, “Opportunities for Growth and Breakthroughs for Cell and Gene Therapies,” 

CGTs offer hope for the future of treatments, but the costly manufacturing, slow turnaround time, and need for supplies hinder progress.

Opportunities for Growth and Breakthroughs for Cell and Gene Therapies

The global biopharma market has experienced a remarkable period of evolution and expansion. In that time, parenteral medications have become one of the industry’s most important innovation and growth drivers.

Fueled by a continuing shift toward at-home, self-administered care—an established trend accelerated by the COVID-19 pandemic—the rapid surge in demand for injectable therapies is set to continue in the coming years. Between 2020 and 2027, sales of parenteral medications are projected to expand from 53–57% of global market volume, with most of those gains taken away from oral drugs (1).

1. Global Data Sales Analytics, May 17, 2021.

Markus Hörburger is product and service manager Secondary Packaging & Device Assembly at Vetter.

When referring to this article, please cite it as M. Hörburger, “Converting Injectable Therapies to Combination Drug-Device Products,” 

Development

The author describes how to seize market opportunities while navigating the requirements of both drug therapies and delivery devices.

Converting Injectable Therapies to Combination Drug-Device Products

The Future Robotics Special Interest Group (SIG) of the DACH (Germany, Austria, Switzerland) affiliate of the International Society for Pharmaceutical Engineering (ISPE) was founded in 2019 and is headed by Richard Denk of SKAN AG and Charly Coulon of Invite GmbH. The group’s aim is to formulate requirements in the pharmaceutical industry and, working in smaller groups, to develop possible solutions for including robotics in a user requirements specification (URS). The group will examine all processes and related issues that are required by robotics or that enable or simplify its use. To this end, an evaluation was conducted with various pharmaceutical companies to determine where robotics could be used most effectively in pharmaceutical manufacturing. A workshop was also held in November 2021, in which small groups discussed further scenarios for the use of robotics. Subsequent ranking of the scenarios then led to the various workstreams. The individual scenarios showed a trend toward the use of robotics in aseptic manufacturing. As a result, the SIG sub-group “Facility of the Future of Robotics for Aseptic Manufacturing” was established. The group brings together all ongoing workstreams related to this topic, with the ultimate goal of achieving fully automated aseptic manufacturing.

1. EC, Draft Revision to “Annex 1, Manufacture of Sterile Medicinal Products,” (Brussels, 2020).

2. BioPhorum, “Robotics Biomanufacturing Roadmap, Draft Version 1,” presentation at the Pharmaceutical Mobile Robotics Conference (London, UK, April 21-22, 2022).

Richard Denk is senior consultant for Aseptic Processing and Containment at SKAN AG. Julien Janda is Head of Process and Technology at Takeda. Markus Stuebchen is Robotics Network Team Lead at Roche. David Wolton is Global Engineering Technology Lead at Takeda.

When referring to this article, please cite it as R. Denk, J. Janda, M. Stuebchen, D. Wolton, “Using Robotics in the Aseptic Manufacturing Facility of the Future,” 

Aseptic Processing

Several steps need be taken to achieve lights-out, fully automated operations.

Using Robotics in the Aseptic Manufacturing Facility of the Future

While a conclusive ‘end’ to the pandemic remains elusive, the transition to a post-pandemic economic model has been defined by a mass ramp-up of various means of digital communication. Digital training tools are one such solution, often allowing companies to effectively prepare employees for the job before they even set foot on-site. While these tools can take on many forms, of particular prominence are augmented reality (AR) and virtual reality (VR) visualization technologies.