Kristin Brooks, Associate Editor03.07.12
While the pharmaceutical industry has been wrestling with cost-cutting restructuring initiatives, the lingering recession, healthcare mandates and patent expiries, R&D has brought forth sophisticated new therapies that have impacted equipment trends. Continuous production, advanced technology, and flexibility, from development to scale up, are in high demand among pharma/biopharma manufacturers. These must-haves are pervasive as they relate to manufacturing, processing and packaging.
To support the latest development innovations in pharma and biopharma therapies, as well as advances or improvments to manufacturing processes, equipment manufacturers are incorporating more flexibility through automation, single-use technologies and user-friendly software.
Equipment Trends
Regulatory requirements, containment of highly potent substances, small batch sizes, personalized medicine, and the use of disposable technologies in biopharmaceutical production: these have all made their mark on the equipment landscape. Dr. Elke Sternberger-Rützel, a Pharma Trendscout for Robert Bosch GmbH, Packaging Technology Pharma Business Unit, said, "To keep pace with advances in drug research and development, such as high-potency treatments, engineering expertise is required to design equipment that can handle, package and secure such substances. Pharmaceuticals, biopharmaceuticals, vaccines and antivirals must be manufactured and packaged with the utmost caution and attention to detail. It is with these requirements in mind that we see four particular trends emerging in the field of pharmaceutical processing and packaging equipment, namely: the ability to handle potent substances; adapting lines for personalized medicine; increasing use of disposable components, and anti-counterfeiting."
So, what are clients are looking for in equipment? They're looking for nothing short of advanced, high-efficiency processing equipment that's easy-to-use, and spans development to scale up. Elle Nolte, manager of Processing Technology at L.B. Bohle LLC, commented, "Manufacturers are looking into technologies that can be used for the development of drug products and then the same unit(s) can be used for production in larger scale, just in longer timeframes. That eliminates a complete step (the scale up to larger production units) in product development. As that saves a significant amount of time during the period the products are under license, profit will rise accordingly. Usually the loss of time in a production process development is inversely proportional to the profit out of it."
For the handling of highly potent drugs, the latest equipment solutions favor the use of automation and robotics technology to reduce human contact with any substances that are being manufactured. According to Dr. Sternberger-Rützel, "Advanced automation has the simultaneous benefits of flexibility (replacing inflexible, standard conveyor belts) and increased line efficiency, further enhancing its attractiveness to forward-thinking drug manufacturers."
Also, tailored drug production for a greater variety of products, with smaller batch sizes and frequent changeover, has led to the need for greater flexibility with manufacturing and packaging solutions. Moving away from standard dosage products, there is a greater need for more product specific packaging using a greater variety of materials. To accommodate these needs, said Dr. Sternberger-Rützel, "The latest solutions are built to withstand frequent changeovers and can be adapted to different types of containers through adjustable robotic handling equipment and operating systems that can be controlled at the touch of a button. The latest filling and closing machines are able to handle different sizes of stoppers, caps and vials, allowing for simple changeovers between low-volume production runs. Flexibility is further enhanced by the ability to switch between different filling systems, including disposable rolling diaphragm pumps, or peristaltic pumps with single-use hoses."
With heightened use of analytical technology, complete automation and real-time monitoring have become must-haves. David Higgs, head of marketing at Malvern Instruments Ltd., remarked, "When it comes to analytical instrumentation, the trend is towards continuous process analysis, a prime aim for many people being the complete automation of control. Customers continue to look to new instrumentation to deliver more information, more efficiently. Ease of use is a major issue for laboratory throughput and as products become more sophisticated, instruments that provide new layers of insight are increasingly important."
He added, "In formulation, development and manufacture, the pharmaceutical industry's use of analytical technology is growing as the industry increasingly focuses on efficient production. This includes the use of process analytical technology (PAT), associated with in- and on-line instrumentation that provides real-time process monitoring."
Currently, some lab hurdles are being addressed by sophisticated programs for machine controls and interactive features with software designed for users of all experience levels. For analytical instruments, intelligent software that fully automates system functions and guides users through the measurement process is proving to add the greatest value. According to Malvern's Mr. Higgs, "Our most recent instrument development programs have focused heavily in this area. For instance, the new Mastersizer 3000 particle size analyzer has software with embedded support that assists at every stage of measurement so that all users – experienced or novice – can make reliable measurements. Today, few users are expert in specific analytical technologies and are required to use many different instruments and methodologies. Lightening the analytical workload with easy to use, intuitive instruments and intelligent software is essential."
Mr. Higgs also noted, "In the process arena the use of in- and on-line analyzers is increasingly widespread but they only fulfill their ultimate potential when used for automated control. Software now exists that enables the development of control architectures that can acquire and use data from a diverse array of different analyzers, eliminating the need for multiple dedicated solutions. This transforms analyzer integration for automated control from being a costly, bespoke task for each individual plant, to becoming a more rapid, routine and cost-effective procedure."
Equipment Challenges
Pervasive regulatory requirements and complicated instrumentation have heightened the need for advanced yet user-friendly solutions.
Matt Hicks, chief operating officer, Federal Equipment Co., a seller of surplus processing equipment, said, "We see a great opportunity for new solutions in aseptic manufacturing and fill-finish activities. These are very complex manufacturing processes and techniques with strict regulatory oversight and manufacturers of these products have made their way into headlines lately because of drug shortages and quality issues. With many new products planed for vials as well as many life-saving products already in vials, we expect to see equipment manufacturers develop engineered solutions to address the problems this segment of the industry currently faces."
Easy operation of highly sophisticated equipment, coupled with processes that are less than par, can also present some challenges. Mr. Nolte at L.B. Bohle said, "Even though processes are sometimes not the best and robust processes that could be developed, clients want to produce AAA products. Lack of time during process development and low level of process understanding very often ends in suboptimal processing with a lot of manual intervention. To straighten that out as much as possible, excellent proportional, integral, derivative (PID) controlled processing has to be developed when changing over to new equipment, which needs simple to operate and highly sophisticated (in terms of control capabilities) operator interfaces and control systems." These controllers are designed to eliminate the need for an operator’s continuous attention, much like autopilot.
In an effort to provide the most efficient and comprehensive processes, some equipment manufactures, as well as technology providers, are combining expertise to create products that address these industry needs. For example, Malvern Instruments, along with collaborators ARTMiS and Powder Systems Ltd. (PSL), have created a new milling suite that incorporates ARTMiS' Automated RealTime Milling System within PSL's containment unit, which is designed to provide a secure, advanced processing solution for highly potent and/or high value materials. ARTMiS brings Sturtevant's Micronizer Jet Mill together with a Malvern Insitec particle size analyzer and the Schenck AccuRate PureFeed Feeder to deliver a fully automated system for jet milling, aimed at providing exemplary process control for optimal manufacturing efficiency. Built on the expertise of all three companies, it's designed to simplify and optimize the jet milling process and reduce operational requirements. "Companies like ours increasingly work in partnership with other technology providers to engineer a complete solution for process analysis and control. Its installation within PSL's advanced containment unit extends all of these benefits to those handling toxic or hazardous materials, such as pharmaceutical actives," said Malvern's Mr. Higgs.
Single Use Technologies
The biopharmaceutical industry is increasingly incorporating single-use technologies to address cost pressures, reduce risk and accelerate the biomanufacturing process. Disposable systems, in addition to convenience, relieve the risk of cross-contamination. Dr. Sternberger-Rützel at Bosch noted, “The trend towards disposable components is a consequence of industry safety regulations, growing use of highly potent substances, and a shift towards smaller batch sizes. The time-consuming process of cleaning, sterilizing and validating product contact parts, particularly during changeovers, has long been a hindrance in achieving operational efficiency. Disposable, pre-sterilized and pre-validated parts including hoses, product bags, filling needles and tubing remove this inefficiency and can eliminate the loss of capacity resulting from lengthy cleaning validation as well as the risk of contamination between batch runs.”
Additionally, low-volume capabilities that allow for using the smallest amount of material possible are essential for analyzing biological materials. Malvern’s Mr. Higgs pointed out, “Low-volume disposable polystyrene cuvettes for analytical instruments, such as the Zetasizer Nano particle characterization system, are enabling the size measurement of very small amounts of sample.”
Disposable trends are on the rise and offer optimal conditions for manufacturing processes. According to Dr. Sternberger-Rützel, “In 2012, pharmaceutical manufacturers will be increasingly drawn to the simplicity and speed of disposable systems, which easily meet industry standards. Assembled in DIN ISO 14644-1 class 7 cleanrooms, the latest single-use components are connected to the product stream via sterile plug-and-play connections and are easily removed, bagged and disposed of without breaking connections and exposing the environment to the product.”
Disposable trends are on the rise and offer optimal conditions for manufacturing processes. According to Dr. Sternberger-Rützel, “In 2012, pharmaceutical manufacturers will be increasingly drawn to the simplicity and speed of disposable systems, which easily meet industry standards. Assembled in DIN ISO 14644-1 class 7 cleanrooms, the latest single-use components are connected to the product stream via sterile plug-and-play connections and are easily removed, bagged and disposed of without breaking connections and exposing the environment to the product.”
New vs. Used Equipment
Investing in new or used equipment varies widely in the industry, contingent upon manufacturing needs, and cost is not necessarily a factor. “Big pharma uses used equipment to a certain extent, where possible. If for any reason a purchase of new equipment is faster, including qualification/validation, most of the time new equipment is the first choice, as time is money,” said Mr. Nolte at L.B. Bohle. “Used equipment can be more expensive than new equipment. The investment is not only the cost of hardware, it’s the overall cost including all planning and integration steps. The cost ratio between hardware and controls/documentation for new equipment for instance is constantly moving to the controls/documentation side. It can be as 50% for the hardware costs and 50% for the controls/documentation cost.”
However, starting from scratch with the installation of new equipment can be more time consuming, particularly for existing manufacturing processes and projects. Mr. Hicks at Federal Equipment noted, “Our customers routinely seek out both new and used equipment depending upon their own manufacturing mix and given opportunities. With a short timeframe to get a new product launched, used equipment becomes a much more viable option over new equipment. If the need is for spares, replacement equipment, or additional capacity with similar equipment, used equipment is always a lower cost option. However, new products sometimes require very specific, custom-built equipment. The more specialized the piece of equipment, the harder it is to source on the secondary market, which favors the purchase of new equipment.”
“For packaging and processing equipment suppliers it is vital to be abreast of the trends and to develop machinery that helps manufacturers deal with the increasing demands of a changing environment, and to develop solutions tailored to meet their needs,” said Dr. Sternberger-Rützel.
Equipment for the latest manufacturing processes, containment solutions for a growing HPAPI segment, flexibility of scale for new therapies such as personalized medicine, and short start-up times and easy changeovers are on trend and equipment providers are charged with designing the equipment that can manufacture and package these increasingly complex drug products. Whether making repairs to existing equipment or purchasing new or used, equipment is integral to a reliable manufacturing process that produces quality product on a regular basis and having all of these options are essential.
Kristin Brooks is the associate editor of Contract Pharma. She can be reached at kbrooks@rodpub.com.
