Recent advances in pharma/biopharma drug discovery and development along with increasingly varied types of products on the market, have had a significant impact on packaging equipment needs. In addition to mainstay matters, such as safety and security, anti-counterfeiting and inspection technology, production rates, changeover time, and maintenance, factors such as expensive and potent drug product and smaller batch sizes, have heightened the need for new capabilities in the fill/finish process. Additionally, space constraints have packagers seeking equipment with a smaller footprint.

The incorporation of more advanced equipment technology is evident at all levels. Whether a pharma/biopharma company is filling/finishing its own products or outsourcing to contract manufacturers and packagers, the need for more flexible equipment to accommodate an expanded range of products is pervasive. To keep pace with packaging needs, equipment manufacturers have had to enhance automation, increase productivity and boost user friendliness, while decreasing size. The latest advances in pharma/biopharma packaging equipment encompass enhanced robotics, anti-counterfeiting and inspection technology/track & trace systems, as well as advances in Overall Equipment Effectiveness (OEE).

We spoke with several equipment manufacturers, as well as contract packagers, to get their perspective on the latest trends and recent advances in packaging equipment. According to Dr. Jérôme Freissmuth, director of business development, product management and marketing at Bosch Packaging Technology, “Rapid development of the emerging markets, progress in drug research, the rise in generics production, the availability of high-potency drugs and innovations in manufacturing processes, will sustainably modify the global pharmaceutical landscape. With these challenges in mind, we see five major trends emerging in the field of pharmaceutical processing and packaging equipment: a rising demand for pharmaceutical quality and safety through anti-counterfeiting and inspection technology; the ability to handle potent substances; adapting lines for small batch sizes and research purposes; an increasing use of single-use components; and the need to improve productivity by optimizing manufacturing processes with respect to OEE.”

Offering a contract packaging perspective, Justin Schroder, senior director of marketing and development services at AndersonBrecon, Inc., said, “The forecasted demand for the existing portfolio of products requires a different model to meet the needs of shorter run volumes, more shared capacity and changeover, as well as smaller footprints of equipment. Likewise, with emerging markets there are many more SKUs to manage and fragmented batch sizes. Equipment has to be flexible and more change-over-friendly, particularly in the contract packaging business where we live or die on the efficiency of our operations. AndersonBrecon maintains an extremely high quality standard, so we are very selective about the machines that support our clients’ products. We see equipment advances in ease-of-use, and at the same time continue to demand higher quality in terms of inspection, safety and reliability.”

Equipment Advances
Demand from pharma/biopharma customers has changed over the years. Among those changes, according to Tim Kram, general manager of Rommelag USA, Inc., are a higher level of aseptic assurance, the need to meet increasingly stringent regulatory requirements, and the move away from preserved products to aseptically produced non-preserved products. Mr. Kram also noted that temperature-sensitive products and secondary inspection equipment are areas where customers are seeking more advanced equipment.

With strict quality and safety standards such as the FDA’s PAT guidance, as well as GMP manufacturing guidelines, regulatory compliance is a top priority. In order to comply with these regulations, the industry requires reliable and high-end inspection technology equipment to be integrated in their production lines. “Manufacturers are continuously challenged to increase output and improve efficiency, as well as inspection accuracy. Therefore, the main focus will be on fully automated solutions for large volume production. Manual and semi-automated devices remain in use for research purposes, customized smaller batch applications and the re-inspection of rejects from fully automated machines,” said Dr. Freissmuth at Bosch.

The increased use of automation and robotics are sought after for several reasons, notably for reducing contamination risk and improving efficiency. Matthias Poslovski, technical sales director at Optima Pharma GmbH, noted, “Most of the isolated incidents of microorganisms found in filling and closing equipment have been proven to have originated from humans. Therefore, it’s understandable that institutions such as the FDA and machine manufacturers strive to automate as much as possible, removing the human factor as a potential source of contamination. At the same time, automated process controls are broadened. Human intervention in a process is being reduced or completely eliminated in fully automated processes. Manual interventions are only then performed (or allowed) during a machine stoppage, and any product in process during the intervention is usually also automatically rejected.”

In addition to preventing contamination, packaging precision is equally important. For example, a new robot control developed by Optima Pharma specifically developed for handling pharmaceutical liquids provides new and flexible methods for pharmaceutical use. “The key is robotic control of fast and secure transport of pharmaceutical liquids in vials and other containers. The goal is to maintain (as best as possible) the geometric volume between the liquid level and the bottle opening (head space), regardless of how the robot moves. Each liquid is unique in its dynamic motion in a vial, based on viscosity, surface tension and filling volume. The robotic control system developed by Optima programmers controls a robot so that the operational speed is no longer limited by the physical parameter ‘liquid.’ In this way, open vials can be transported at a high rate of speed, resulting in reduced cycle times,” according to Mr. Poslovski.

To enhance compliance, as well as a myriad of other issues, manufacturers are also increasingly drawn to the simplicity and speed of single-use systems. According to Dr. Freissmuth at Bosch, “Easily meeting industry standards, 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. Market-leading experts offer ready-to-install-solutions that can easily be validated. They are precise and safe, and allow significant time savings on product changeovers.”

In addition to ease of use, single-use systems can also save space. Suzy Arrasate, marketing manager at Cozzoli Machine Company, noted, “One of our developments is the re-designed VR2PP Series, high performance aseptic liquid filling machines using peristaltic pump technology that utilizes the latest innovations in single-use technology. Designed with Class 100 clean rooms in mind, the VR2PP Series uses a straight-line concept with a small footprint and is built for reliability, easy operation and accuracy.”

Another common requirement for manufacturers is smaller packaging equipment with all of the advantages of larger, automated machines that also provides ease of use and flexibility. According to Kim Norris, sales projects coordinator at ESS Technologies, “Packagers are looking for smaller, more flexible automated packaging systems. ESS sees numerous requests to fit the packaging line into ever-shrinking spaces. Compact ‘mini,’ monoblock fillers/cappers offer the same functionality and productivity of a full-sized system in a footprint that is smaller by 30% or more. Packagers are also looking to greatly reduce the amount of time a packaging line takes to changeover from one product to the next. Today’s packaging machinery can be designed to require fewer change parts by using the same tooling set for multiple products. In some cases, changeover settings can be programmed into and accessed from the PLC (Programmable Logic Control), allowing the machinery itself to enact the size changeover. This is especially true in robotic systems where the robot and PLC can be programmed to perform an automatic tool changeover.”

Packaging Precarious Products
Increased use of highly potent and cytotoxic substances and personalized medicine requires highly specialized packaging equipment incorporating isolators, automation, and versatility. These products present new challenges in the handling and containment of these substances to protect both the drug product and personnel from contact with one another, requiring as little manual intervention as possible. Dr. Freissmuth at Bosch noted, “The latest equipment solutions favor the use of automation and robotics technology to reduce human contact with any substances that are being manufactured. Also, as a result of the increasingly strict regulatory guidelines, manufacturers increasingly rely on the use of barrier technology such as isolators.”

Bob Mac, marketing manager at Sharp Corporation, noted, “The emergence of thin film pouching of controlled drugs is a recent trend in the industry. The equipment we have in-house is a Harro Hofliger PML 100 machine that could slit the film and pouch it on the same machine. Also, if a potent product can be manufactured into a ‘roll film’ format, then that product can run on this machine, as well.”

With the increasing trend of very expensive drug products, along with smaller batches, it’s becoming more and more important to extract every last drop of a batch into a vial or syringe. According to Mr. Poslovski at Optima, “The use of gravimetric IPC, from intermittent sampling IPC to 100% IPC over the years has proven itself as an important basis for accurate filling and getting the most out of a batch of product. It is to be expected, that IPC systems will be used more often, as well as in smaller machines.” 

Also, more flexible processing and packaging solutions are needed for personalized medicine products. “Smaller batch sizes shift the emphasis from speed and mass production of standard dosage products to more individualized products packaged in high-quality materials. Short start-up times, easy changeovers and a high degree of automation are key considerations. New machinery demonstrates the possibility of covering almost the entire manufacturing process in one single machine, thereby dramatically reducing investment costs,” said Dr. Freissmuth at Bosch.

Accommodating changing needs such as product sensitivity pared with increased efficiency requires even greater sophistication of equipment. “As the biotech market has grown and expanded, we do see more demand for parenteral delivery forms. This may be transdermal patches, topicals, or injectibles such as vials and syringes. These are often high value products and require speed and accuracy balanced with careful handling. We have also seen commercialization of auto-injector or pen style injectable devices that can be quite intricate. We employ some sophisticated and very precision oriented equipment to support these types of delivery forms,” said Mr. Schroder at AndersonBrecon. “With oral solids we see a shift from traditional pressed tablets and capsules to products such as quick dissolve tablets, soft-gels and liquid-gels. These all have unique characteristics and challenges. You can imagine the implications on your high speed filling line if you break a liquid-gel.” Controlling the way these products behave in a high-speed packaging environment requires a great degree of accuracy, which is at the forefront of today’s equipment technology.

Additionally, many parenteral delivery forms by nature are high value and require cold chain logistics. “We have to be extremely careful in the packaging process to maximize yields, as these therapies are very expensive,” added Mr. Schroder. “With the Cold Chain storage, products have a finite amount of time they can be out of the cold environment. Some products do not have any allowable excursions, and in those instances we are packaging in an environment of 2-8°C, which can create its own challenges for process, staff and equipment.”

Overcoming Challenges
Overall Equipment Effectiveness (OEE), inspection technology, and track and trace are all mandatory aspects relevant to packaging processes. OEE evaluates and indicates the effectiveness of a manufacturing operation by defining the performance, availability, and quality of one piece of equipment, or an entire production line, and provides a pathway to improve it. Measuring and tracking OEE is essential for success and there are many off-the-shelf systems available.

To maintain and improve a plant’s OEE, aftermarket services for equipment providers are essential. According to Bosch’s Dr. Freissmuth, “OEE is equally important when it comes to the development and market introduction of new pharmaceuticals. So far, the production of small batches has been quite an expensive venture. But with the optimization of machines in terms of flexibility, automation, easy changeover and scale-up, the situation has changed significantly. These improvements enable manufacturers to develop new drugs with short time to market, while complying with strict regulations. A processing and packaging specialist who wants to keep pace with the industry needs to offer comprehensive engineering and consulting services all over the globe.”

To enhance OEE, many manufactures are looking to install packaging machinery that includes PackML (Packaging Machine Language) to help provide seamless operations. “The primary objective of PackML is to bring a common ‘look and feel’ and operational consistency to all machines that make up a packaging line. A machine programmed with PackML is better equipped to provide data on OEE and Root Cause Analysis (RCA) on the system, which helps packagers understand and manage the efficiency of their packaging line,” said Ms. Norris at ESS Technologies.

Additionally, the omnipresent threat of counterfeiting requires advanced track and trace packaging technology and represents a major component of today’s equipment and various solutions are available that can be integrated with existing equipment platforms. According to Ms. Norris, “ESS has noticed manufacturers are requesting track and trace systems with greater frequency. This requires the packaging machinery to be integrated with commercially available track and trace system components, such as coding devices, code readers, and a means to record the data. Case packers can be integrated with track and trace systems to record each individual unit as it is collated and packed, allowing the manufacturer to track the contents of each case. Pallet cells can also be integrated with track and trace systems to track each case as it is loaded on a pallet.”

Mr. Schroder added, “AndersonBrecon is continually pushing the envelope to maximize product safety and security. This involves multilayered inspection throughout the packaging process to ensure product is meeting the highest standards for quality, with redundant systems at each phase. This is further continued with the introduction of anti-counterfeiting technologies, serialization on packaging and the aggregation of packaging with data handling. This really magnifies the level of sophistication on any particular packaging line. We support several clients and their products and on any given piece of equipment, and each client’s requirements can vary.”

Furthermore, the imminent legislative requirements for unit-level serialization are new territory for customers and suppliers alike, and packagers need to implement a number of changes in a short time period to meet looming deadlines. According to Chris Siegele, market research analyst for Omega Design Corp., “We foresaw the oncoming unit serialization need and, since 2008, have worked to develop a complete array of line-level solutions, in partnership with some of the industry’s leading purveyors of serialization software. This equipment is production ready and has already seen overseas deployment.”

Providing flexible solutions that meet various client needs is crucial in today’s packaging environment. Equipment manufactures must anticipate these needs and provide solutions to meet them. Dr. Freissmuth at Bosch noted, “More than ever, manufacturers face the challenge of anticipating which products will be required next. This is why new machinery must be future-proof, have scalable and flexible platforms, handle different formulations, and be capable of processing many packaging styles like syringes, vials and cartridges. Moreover, equipment providers will be well advised to increase their services in terms of formulation and development support.”

Packaging equipment is evolving to encompass increasingly challenging parameters, from varied drug products, small to large-scale production, sensitive, high-value toxic substances, and accommodating manufacturers needs for a smaller footprint. Greater scale automation and robotic technology are fast becoming the focal point of all packaging lines, offering immediate advantages, such as an increase in yield and reduction in production costs. Equipment manufactures stay ahead of the game by developing products to incorporate more flexibility and adaptability. The result is highly sophisticated equipment designed to prevent contamination, enhance packaging precision and minimize product loss.