Pharmaceutical and biopharmaceutical manufacturing equipment covers an array of processes, from drug production to filling, and includes containment and inspection systems as well as accessories, all of which must comply with stringent requirements to meet industry standards for good manufacturing practice (GMP). Today, many of these processes can be automated, further improving product quality and manufacturing operations.

Efficiency, changeover time, production yields, and of course, flexibility remain key drivers for today’s manufacturing equipment to keep up with pharma and biopharma pipelines and R&D trends. Leveraging data, automation, and digitalization, as well as energy use and sustainability targets, are some of the key trends impacting manufacturing and equipment.

Meanwhile, changing existing manufacturing processes takes time in a highly regulated industry. For example, overcoming validation challenges associated with continuous manufacturing is necessary for the adoption of the technology. In the meantime, the latest manufacturing equipment is helping to improve the capability to handle a wide range of drug products and batch sizes, increasing flexibility and semi-attended operation.

Pharma & Biopharma Trends

Specialized treatments and growth in cell and gene therapies continue to drive new equipment developments, along with having the flexibility for both small volume and bulk production, and improving overall efficiency. Dr. Andreas Mattern, Vice President of Strategy & Global Product Management Pharma at Syntegon, said, “While blockbuster medicines and traditional, large batch drugs continue to be important contributors to human health, personalized medicine is quickly becoming the focus for future treatment breakthroughs. These, in turn, require production in ever smaller batch sizes.”

Cell and gene therapies are largely being studied in oncology and rare disorders and are often delivered parenterally. According to a report from The Alliance for Regenerative Medicines, and pipeline data derived from Pharmaprojects, nearly 1,200 cell therapies were in preclinical development in 2021, a 31% increase over prior year, and for gene therapies, more than 1,240 were in preclinical development in 2021, representing a 35% increase over prior year.^1,2 

While an exact definition of “small batch” does not exist, Dr. Mattern noted, interpretation taken from the FDA’s “Guidance for Industry, ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers,” for generic parenterals lists small batches as at least 10% of the proposed maximum size commercial batch or less than 15,000 – 60,000 containers, based on fill volume. Batch sizes shrink to a few thousand containers for parenterals used in clinical trials, and for highly specialized treatments such as autologous cell therapy, one patient equals one batch of approximately 5-10 containers.

According to Sigma Mostafa, Ph.D., Senior Site Head at KBI Biopharma, a global contract development and manufacturing organization (CDMO) offering process development and clinical and commercial cGMP manufacturing services for mammalian, microbial, and cell therapy programs, there are four biopharma trends impacting manufacturing equipment: the push for increasing the amount of product produced from existing equipment and reducing manufacturing cost; ensuring that the process consistently achieves the Quality Target Product Profile (QTPP); implementing data collection and analysis for improved control and outcome from manufacturing; and incorporating sustainability goals within the manufacturing process. 

Similarly, for oral solid dose pharmaceuticals, increasing product production and operational efficiencies are key for manufacturing equipment. Frederick Murray, President of KORSCH America Inc., a provider of tablet press technology solutions, said, “A clear emphasis on improving overall efficiency through gains in output, changeover time, and production yields remains a key driver. Also, of increasing interest are integrating tablet presses to a central manufacturing network to facilitate operator login through the domain, centralized product recipe management, centralized batch data storage, and the transfer of key process parameters to a central SCADA or iHistorian.”

Another fast-growing trend is flexibility for ready-to-use (RTU) containers. According to Dr. Mattern, “This trend calls for dedicated production platforms with fast batch changeovers and the lowest possible product loss. At the same time, pharmaceutical manufacturers require utmost flexibility in the use of containers. Drug manufacturers benefit from reduced time-to-market and total cost of ownership (TCO), as well as increased flexibility and greater integrity of the drug product. While RTU containers have been the de-facto standard for pre-filled syringes for some time, they are now increasingly being used for vials and cartridges in both bulk and small batch applications,” Dr. Mattern said.

According to market research by P&S Intelligence, the market size for RTU vials alone reached $306.5 million in 2020, and with an estimated market growth rate of 14.5% CAGR will reach $1.2 billion worldwide by 2030.³ Factors for this market growth include the need for pharmaceutical companies to increase operational efficiency and growing usage of injectable drugs.

Addressing Manufacturing Challenges

Several areas pharmaceutical manufacturers look to address current challenges include increased productivity, isolator biodecontamination, and sustainability in operations.

The pressure to increase productivity without facility expansions means higher efficiencies are required according to Frederick Murray of KORSCH America Inc. “There are opportunities to increase production output by as much as 30% on some products simply by leveraging an exchangeable turret, which offers an increased number of punch stations (TSM BB or BBS). An additional turret strategy also permits tooling to be installed offline, further streamlining changeover. Investment in a second set of product contact parts to facilitate a faster changeover is an important consideration in an environment with smaller batches and more frequent changes,” Murray said.

With the increase in biologics development and manufacturing more and more isolators are being used in the industry and according to Dr. Mattern of Syntegon, biodecontamination is a challenge. He explained, “It is an essential step before the actual fill-finish process and involves exposing the surface of an isolator to a specific concentration of decontaminant for a set period to create an aseptic atmosphere within the process core. Syntegon offers an approach using vaporized hydrogen peroxide that spans four phases: preparation, conditioning, biodecontamination, and aeration. The goal is to achieve a residual H2O2 concentration of typically 1 ppm (parts per million) or less before production begins. From the first automated biodecontamination in the early 1990s to today’s solutions, the biodecontamination cycle has shrunk from 10 hours to less than 60 minutes for fully loaded commercial isolator lines,” said Dr. Mattern. This approach is designed to speed up processes and leave more time for the actual production as well as contribute to more energy-efficient operations.

Additionally, in light of efforts to minimize environmental impact and resource consumption, some companies are setting ambitious sustainability targets. However, energy-intensive equipment such as sterilization tunnels present enormous challenges, according to Dr. Mattern. “Sustainable use of energy and other resources is currently one of the greatest challenges in the pharmaceutical industry – not just since the rapid rise in energy prices. To help pharmaceutical manufacturers master the balancing act between energy efficiency, consistent quality, and validated parameters, Syntegon developed a method for determining and evaluating emissions from equipment over its entire life cycle – the Life Cycle Assessment (LCA),” said Dr. Mattern. This software-based calculation model covers parameters such as electricity, compressed air, media, and packaging materials.

Advances in Manufacturing Equipment

Automation and digitalization are gaining momentum in the industry, driving advances by improving product quality, providing greater protection, and optimizing operations. Additionally, new equipment technologies are helping to achieve increased efficiencies and continuous manufacturing processes.
 
Sigma Mostafa of KBI Biopharma, said “Manufacturing facilities are becoming connected and efficient as automation and digitization tools are being implemented to create smart factories. For example, KBI Biopharma’s Patriot Park commercial manufacturing facility is vertically integrated. The ERP, LES, MES, and automation layer are fully integrated to support digitized business processes. Additionally, full electronic batch record allows for review by exception.”

According to Dr. Mattern of Syntegon, automation and digitalization are highly sought after in the pharmaceutical industry. “The use of robotics is taking the industry a huge step further towards even higher product protection and quality, as it eliminates the main cause for contamination, i.e. human intervention. On the other hand, digitalization makes it possible to monitor machine conditions in real time, which helps drug producers make data-based decisions and optimize operations,” said Dr. Mattern.

Meanwhile, continuous manufacturing technologies for oral solid dose forms has been trending for several years but implementation in the highly regulated pharmaceutical industry requires investment in time and the right equipment to change existing processes.

Frederick Murray of KORSCH America, said, “The validation challenges and capital investment associated with continuous manufacturing continue to limit the adoption of the technology. A new class of mid-range tablet presses – ideal for small batch production and frequent changeovers – has addressed a critical need in the market by enabling higher overall efficiencies.”

Murray added, “The improved capability of inline tablet testers to handle a wide range of tablet shapes and sizes has increased the opportunity to realize semi-attended operation. High-speed, high-volume double-sided tablet presses are also more flexible in terms of seamless conversion from single- to bi-layer, and the turret exchange sequence has been significantly simplified to support increased OEE.”

Syntegon recently introduced its fluid bed lab unit Solidlab 2 Plus for the development of both batch and continuous manufacturing processes. According to Dr. Mattern, “When combined with a feeder-blender unit, the Solidlab 2 Plus becomes the Xelum R&D, Syntegon’s development platform for continuous manufacturing. Process parameters from the Xelum R&D can be transferred directly to the Xelum production unit. The latter doses, mixes and granulates individual packages, so-called X-keys, which continuously run through the process chain and are removed from the system successively. This way, even smallest amounts of APIs of less than one percent can be dosed precisely.”

Coinciding with changing pharma and biopharma manufacturing needs and the growing desire to adopt innovation, equipment developments are increasingly driven by data transparency and automated systems with greater flexibility and customization. Additionally, next generation manufacturing facilities are also expected to contribute to sustainability. 

References

1. http://alliancerm.org/wp-content/uploads/2021/08/ARM-H1-2021-Report.pdf
2. https://pharmaintelligence.informa.com
3. www.psmarketresearch.com/market-analysis/rtf-rtu-vials-market-trends