Evolving Pharma/Biopharma Trends
The continued evolution from mainstream, mass produced pharmaceuticals to more specialized therapies, has required a complete concept change in manufacturing and processes for pharma companies. “Highly specialized products in small quantities and different drug delivery systems present a challenge for pharmaceutical companies,” said Jan Deininger, editor at Optima. “It makes a change in thinking necessary since niche products require a completely different production process than blockbuster pharmaceuticals. Pharmaceutical companies that produce small quantities need flexible machines that can process small batch sizes and different container types. At the same time, it is essential to maintain the high level requirements for product quality and patient safety,” Deininger noted.
As a result, the demands on the flexibility of equipment systems are increasing. For example, she said smaller batch sizes have to be mastered and different containers such as syringes, vials and cartridges have to be filled on a single line.
With more niche products coming to market, Tim Saarinen, chief operating officer for Maruho Hatsujyo Innovations (MHI), said, “The number of products and product packaging to achieve different presentations to the end user has been increasing. With fewer blockbuster products and more moderate scale products coming through the pharmaceutical pipeline, companies are more anxious to differentiate products based on customer experiences.”
Meanwhile, eliminating the risks associated with exposure to highly potent or cytotoxic drugs requires high containment equipment solutions. Kat Jones, PCI’s director of marketing and commercial operations, said one of the largest trends in recent years has been unprecedented growth in the number of molecules being classified as “potent,” primarily driven by the oncology market, as well as therapy areas including pain and CNS disorders. She said, “Such molecules require special handling to protect both operators and the environment, and although historically as an industry we have relied on personal protective equipment (PPE), guidelines including those issued by the International Society for Pharmacoepidemiology (ISPE) indicate that preferred and best practice solutions should include contained engineering equipment whereby the molecules themselves are subject to full containment through the use of technology.”
Additional industry trends impacting equipment are continuous manufacturing and digitization in an effort to optimize processes. Andreas Mattern, director of product management, Pharma, at Bosch Packaging Technology, added, “The pharmaceutical industry is changing and developing at an unprecedented pace. On the one hand, important developments in biologics, for instance for the treatment of cancer or orphan diseases, are entering the market. On the other hand, the development of continuous manufacturing equipment for oral solid dosage (OSD) is opening new potential for optimum API dosage and faster time-to-market. Moreover, digitization is also gradually entering the world of pharmaceutical production and is about to change the way we work significantly.”
Digitization, often referred to as Industry 4.0, is a comprehensive automation, business information, and manufacturing execution strategy aimed at improving the industry via the integration of all aspects of production and commerce across a company for greater efficiency. Similarly, the internet of things, or IoT, is a system of interrelated computing devices, mechanical and digital machines, or people that are provided with unique identifiers (UIDs) and the ability to transfer data over a network without requiring human-to-human or human-to-computer interaction.
Pharma and Biopharma companies increasingly look for services and capabilities that span R&D through to manufacturing, filling and packaging. Addressing the need for small to large scale manufacturing, isolator technology, integration options for multiple dosage forms, all while saving time and space, results in increasingly complex and versatile equipment.
Matt Bundenthal, director of sales and marketing for Fette Compacting America, said, “Those exploring continuous manufacturing look for equipment that is not only applicable in terms of capacity capabilities, but also integration-friendly (notably in cases where the equipment making up the full train is sourced from different suppliers).” He added, “A more general requirement is for maximum versatility in any machine. Budgets are tighter than ever and everybody wishes to have tablet presses and encapsulators that can produce the greatest number of applicable dosage forms and sizes.”
Optima Pharma develops and implements complex systems with technologies filling and closing, isolator technology and freeze drying, in central responsibility. According to Deininger of Optima, this includes digitized planning, integrated Factory Acceptance Test (iFAT), site management, Site Acceptance Test (SAT) and comprehensive services. “The Comprehensive Scientific Process Engineering (CSPE) method is used to ensure that as little time as possible elapses from order to start of production,” she said. “The combination of scientific methods and technological processes revolutionizes the planning and realization of pharmaceutical filling equipment.”
Multiuse machines are most in demand as they process different primary packaging materials, such as vials, syringes, cartridges, including ready to use components, designed with a minimum space requirement. According to Deininger, “Users will also save time due to the adjustable transport system that does not require any format parts. A variety of technologies minimize product loss. Re-dosing upon request, short hose lines, 100%-In-Process-Control for vials, syringes and cartridges, weigh-dosing, re-capping upon request, and much more.”
Pharma/Biopharma companies are thinking about manufacturing as well as packaging formats, particularly for biologics. Mattern of Bosch Packaging Technology, said, “New biologic developments call for flexible equipment that can handle ever smaller batches, while adapting to new products and packaging formats quickly.” He noted that pharmaceutical manufacturers are not simply looking for one machine, they’re looking for a partner who can accompany them throughout their projects. This can start as early as the R&D phase and go all the way to production and packaging, as well as include the underlying software requirements, qualification and validation support and service packages.
“Consequently, the focus has shifted from merely technology-driven projects to complete solutions—including market expertise, innovative concepts and the flexibility to adapt to very specific and unique requirements. Such projects require a lot of time, experience and motivation,” Mattern said.
Equipment down-time tops the list of challenges that clients look to overcome. Leveraging digitization can help pharma/biopharma companies more accurately assess manufacturing operations, but implementation comes with its own set of challenges, particularly in an industry that faces strict regulatory requirements. Bundenthal of Fette Compacting America, said “Equipment down-time is a universal challenge—one that has led to the establishment of prevalent topics such as Overall Equipment Effectiveness (OEE). Capital equipment such as a tablet press or encapsulator represents a significant investment for any client, but especially for those fighting against thin budgets.
It is therefore imperative to find new methods for maximizing the amount of ‘up time’ that any piece of equipment offers. Every moment that a high-speed machine sits idle represents lost opportunity and revenue.”
Mattern, of Bosch Packaging Technology, said, “Digitization, Industry 4.0 or IoT—no matter what you want to call it, it’s all about using existing data to optimize processes, make them more transparent and more efficient. The pharmaceutical industry must overcome specific challenges compared to other industries because of the very strict regulations regarding safety and product quality.”
In digitization projects, the first step is making the existing data visible in the first place. He explained how the digitization process works with two of Bosch’s products, “Our Pharma i 4.0 Starter Edition provides plant operators with essential data on their OEE, for condition monitoring of plant status or processes, and on important events like alarms or downtimes, in real time. The Pharma i 4.0 Starter Edition monitors single machines and several lines simultaneously. Once the data is available, data analyses, for instance Bosch’s Data Mining service, can help to identify new potential for higher production transparency and optimization.”
Data mining makes it possible to assess information more effectively to identify and remedy the root causes of faults. He added, “In general, the data from two production batches is already sufficient to draw first conclusions. The more data that’s available for evaluation over a longer period, the more details will come to light.”
With the growing number of biopharmaceuticals on the market, product and operator safety has become increasingly imperative. Equipment manufacturers have made great strides when it comes to the containment of high potent and cytotoxic compounds. Jones of PCI said, “Technology has advanced considerably in recent years, with manufacturers constantly evolving the solutions available. The area of contained engineering solutions whereby the molecules themselves are fully contained at every stage of the process, thereby reducing the risk of exposure to operators and the environment, is probably one of the most significant developments in recent years. This combined with geometrically similar equipment to aid scale-up and reproducibility has changed the way we are able to manage these often very potent molecules.”
Mattern of Bosch Packaging Technology, added, “In the production of oral solid dose forms (OSD), the need for small batch equipment with appropriate containment has also evolved in parallel with the high potency of the drugs.” Active Pharmaceutical Ingredients (APIs) can be classified into occupational exposure bands based on their potency. Categories are often referred to as OEB 1 (low hazard); OEB 2 (moderate hazard); OEB 3 (high hazard); OEB 4 (very high hazard); and OEB 5 (extremely high hazard). The new Bosch GKF 720 capsule filling machine has been developed for OEB 5 containment and is designed to ensure the highest protection for the operator, machine and product. Mattern added that the machine’s minimal water requirements, defective capsule detection and compact design can help with cost savings.
According to Mattern, the development of continuous manufacturing equipment for OSD is opening new potential for optimum API dosage and faster time-to-market. Bosch recently introduced its new Xelum R&D to the market. The Xelum system doses mixes and granulates individual packages, so-called X-keys, which continuously run through the process chain and are removed successively from the machine into bins. Mattern said, “This way, even smallest amounts of APIs of less than 1% can be dosed precisely. It relies on the unique technology developed by Bosch’s subsidiary Hüttlin.
Instead of the usual twin screw granulators, the Xelum platform works with well-established fluid bed processors for optimum granule quality.”
Tremendous advances have been made in the area of capsule filling with respect to smaller footprints, increased yield and reduced costs. According to Bundenthal of Fette Compacting America, some of the most novel advances are servo-driven encapsulators. “By moving away from those that mechanically couple all of the sub-processes within the machine, one achieves a far greater degree of control over the entire process. Overall efficiencies can therefore increase dramatically. Some suppliers are even offering a double-sided encapsulator, which is entirely unprecedented. Such a machine can offer output of up to 400,000 capsules per hour—roughly twice that of the next fastest option,” Bundenthal said.
While recent equipment innovations are dramatically improving manufacturing processes, demand for all encompassing flexibility continues. “Our customers increasingly wish for their machine solutions to cover a wide range of requirements: large and small batch sizes, ready to use syringes and bulk products, expensive and low-priced products, all possible container types such as syringes, vials, cartridges and special devices,” said Deininger of Optima. All this requires a high degree of flexibility and highly sophisticated solutions.