Hallie Forcinio is packing editor for Pharmaceutical Technology and Pharmaceutical Technology Europe, editorhal@sbcglobal.net.

Hallie Forcinio

Exhibitors in the Healthcare Packaging Pavilion at PACK EXPO International (Oct. 23–26, 2022, McCormick Place, Chicago) focused on integration, automation, and service (along with sustainability). A growing number of original equipment manufacturers (OEMs) are emphasizing integration capabilities. Assuming single-source responsibility for a turnkey packaging system or entire line can simplify specification, installation, and startup for pharmaceutical manufacturers and overcome gaps in in-house knowledge and manpower.

ProMach’s Pharma business unit exhibited an integrated line that included equipment from four of its brands – NJM, Pharmaworks, Serpa, and WLS – as well as systems from partners and other OEMs. “There is growing demand for our integration services as many manufacturers and contract packers with pharma, nutraceutical, ophthalmic, and animal health products have fewer resources in-house to manage line integration,” said Tom McDaniel, president of ProMach Pharma (1).

The line packages aseptic kits, which contain a vial and a syringe. It begins with a Dara NFL/2 system filling and closing ready-to-use syringes and vials. An NJM Courser 230 labeler applies labels to the syringes, while a WLS VR-72 labeler handles the vials. A robotic pick-and-place unit from PharmaMed feeds one syringe and one vial/cycle to a Pharmaworks TF2 blister machine. After sealing, a linear transport from Beckhoff conveys the blister-packed kits to a Serpa P100 horizontal cartoner, followed by a Serpa P200 case packer. Labels for the syringes and vials are printed offline on an Autonomy digital label printer from WLS (1).

In another example of line integration, ESS Technologies developed an integrated, automated cartoning/case-packing system for COVID-19 vaccines. Upstream vial labelers were integrated to deliver 150 10mL vials/min to a Model VC30 cartoner. A servo collation system arranges vials in a two-by-five pattern as a Fanuc SR-6iA robot with vacuum end-of-arm tooling (EOAT) erects auto-bottom cartons and places them on the carton transport conveyor. If required, a Fanuc SR-3iA robot erects and inserts a partition into the carton. Then a Fanuc LR200iD robot equipped with vacuum EOAT picks up the 10-count collation and places it in the erected carton. A second Fanuc SR-3iA robot picks and places a leaflet on top of the vials before the carton flaps are folded and closed (2).

A Fanuc LR200iD robot picks and places closed cartons so an integrated coder can print lot/expiration date codes and an integrated camera system can inspect the printed code. Cartons with non-compliant codes are rejected. Cartons with good codes are placed on the infeed to the case packer. The compact CEL5 case packer integrates a Fanuc M-20iA/20M robot with custom, ESS-designed EOAT to erect a regular slotted case and place it on a vacuum plate for loading. Cartons are collated into a two-by-three pattern as the robot erects the case. Using vacuum EOAT, the robot picks and loads the collation into the case and repeats the process to add a second layer. Filled cases travel to a unit that folds the top flaps and tapes the top and bottom of the case. An integrated corner-wrap print-and-apply labeler applies labels to sealed cases (2).

The best integration and automation will not deliver optimum performance without regular service. To provide the needed expertise and manpower, OEMs are launching service programs. Syntegon, for example, has established multiple service levels so end users can select a fixed-price program that matches their needs for maintenance, spare parts management, remote service, and training. The Syntegon Service Agreements include Synexio cloud-based software that monitors and evaluates machine and production data. The real-time information can be used to streamline maintenance processes and enhance overall production efficiency (3).

1. ProMach Pharma, “ProMach Pharma Showcases Line Integration Services,” Press Release, Aug. 16, 2022.

2. ESS Technologies, “Packaging Line for Vaccine Vials Meets Urgent Demand for Production,” Press Release, undated.

3. Syntegon, “Versatile System Solutions for the Future: Syntegon Presents Broad Brand Portfolio at PACK EXPO,” Press Release, Aug. 25, 2022.

Articles

Address needs for integrated, automated systems and service. 

Trends at PACK EXPO

Consumers favor sustainable products. A survey by Shorr Packaging shows that 76% of shoppers surveyed have made a conscious effort to purchase more sustainable products in the past year. An even stronger majority, 86%, are more likely to purchase a product from a brand or retailer if the packaging is considered sustainable. Additionally, 77% expect more brands/retailers to offer 100% sustainable packaging for their products soon (1).

When shopping, 64% of the consumers surveyed consider whether the packaging can be recycled; 60% look for packaging with recycled content; 60% seek source-reduced designs (no overpackaging); 45% want biodegradable packaging; and 28% like paper-based packaging. Approximately 68% are open to switching to a brand that offers sustainable packaging. This is particularly true of younger consumers (1). A report from Euromonitor International comes to the same conclusion, noting Millennials and Generation Z feel they can make a difference through their choices. This largest spending cohort of the future will rely on tech tools, such as digital product labeling and mobile tracking apps, to check environmental claims and ensure minimal climate impact (2).

Clear labeling of sustainability attributes also is important, with 69% saying they are more likely to purchase a product when there’s clear language/symbols on the packaging that states it uses sustainable materials (1). With recyclability, recycled content, and biodegradability top-of-mind, paper-based packaging ticks all the boxes and is favored by almost one-third of the consumers in the Shorr Packaging study.

To meet this demand, Keystone Folding Box has completed a $5 million upgrade that boosts capacity by 20% for its product line that includes secondary blister packages made from recyclable and compostable paperboard. Its Ecoslide Series of blister packs features a safety feature that provides the most stringent F=1 child resistance while eliminating the need for a two-step “peel/push-through foil,” which many consumers find difficult to open. Including Ecoslide-OTC for over-the-counter medicines as well as its signature Ecoslide-RX pack for prescription drugs, the sustainable package platform reduces the amount of disposable plastic needed for peel/push CR blisters (3).

Blister cards themselves also are becoming more sustainable. TekniPlex Healthcare has launched a fully transparent, recyclable, mid-barrier blister package. Certified via third-party testing, the recyclable polypropylene (PP)/cyclic olefin copolymer/PP base material with barrier PP lidding is said to be a first in the healthcare industry. From a manufacturing standpoint, initial machinability analyses have been positive, with large-scale tests scheduled. TekniPlex Healthcare also has premiered a fully recyclable polyester mono-material blister. It’s suitable for products that do not require barrier protection (4).

Incorporating post-consumer-recycled (PCR) content in packaging is viewed as highly desirable by the industry and consumers, but can pose challenges due to supply chain and quality issues. Avient’s PCR Color Prediction Service for polyolefins and polyethylene terephthalate (PET) resins and Cesa Nox A4R Additives for Recycling eliminate the trial-and-error of adopting PCR content and associated color choices. The PCR Color Prediction Service helps brand owners understand what colors are achievable based on the amount of PCR used. Proprietary software determines—through prior color matching—what colors are feasible in an application that incorporates PCR content. It also calculates how much PCR content can be added without affecting the package’s signature color. The faster evaluation process is particularly helpful if it becomes necessary to switch sources of PCR material (5).

The Cesa Nox A4R Additives for Recycling protects PCR polyolefins against oxidation, which can lead to defects like black spots, gels, and
discoloration. The antioxidant can be added to PCR content early in
the recycling process or incorporated in virgin resin to prepare it for
future recycling (5).

Schreiner MediPharm has set goals to increase its use of recycled/renewable materials, including the simplification of disassembly for recycling and reducing carbon dioxide emissions. As a result, it recently introduced more sustainable options of its Pharma-Tac label for infusion bottles and its Autoinjector-Label. Both new designs rely on film materials that are either recycled or produced from renewable raw materials. Extensive in-house testing shows the more sustainable materials perform as reliably as conventional substrates. For example, the Pharma-Tac label passed load and gravitational trials, and both the hanger label and Autoinjector-Label passed tests for adhesion, ink adhesion, print durability, and laser marking viability (6).

More sustainable tube options also are available. Hoffmann Neopac now offers Neopac mono-material barrier tubes, which are recyclable in the polyethylene (PE) or PP material stream. Neopac’s Polyfoil MMB mono-material barrier tubes have undergone successful testing by RecyClass, an initiative of Plastics Recyclers Europe. MMB structures, with and without thin film metallization, met recycling requirements set by the US-based Association of Plastic Recyclers (7). The MMB tube can reduce packaging carbon footprints by up to 38% compared to traditional laminated tubes. The tube body is made possible through a first-of-its-kind adhesive-laminated process, an alternative to conventional blown-film and extruded-film methods. Key advantages include advanced barrier and aesthetic options in the tube body. The tube’s shoulder and cap are made with low-melt-flow-index high-density PE and only 2% foreign material (8).

However, the majority of tubes used in Europe are aluminum barrier laminates (ABLs). These multi-material tubes currently cannot be industrially separated and recycled in existing recycling facilities. To solve this problem, Hoffmann Neopac has partnered with Saperatec, which has developed washing technology and established a pilot plant to separate the PE and aluminum for recycling in existing facilities. A laboratory study at Saperatec in spring 2021 with various ABL tubes from Neopac showed that its Polyfoil tubes can be completely separated (8).

“In addition to the already existing environmentally friendly and recyclable tubes from our EcoDesign portfolio, we are committed to a recycling solution for our conventional Polyfoil ABL tubes,” said Peter Bossert, head of materials development at Hoffmann Neopac. “With this new initiative, we will offer our customers the best possible balance between product safety and sustainability. As early as this year, we will make a portion of our production waste available to Saperatec to demonstrate its recyclability on an industrial scale, per the promising laboratory tests that have been performed. With the pending recycling of ABL tubes, we are closing a recycling gap in our portfolio.” After testing the separation of production waste, Neopac and Saperatec plan to study the possibility of using the separated materials in the production of new tubes (8).

Saperatec began construction of its industrial separation facility in December 2021 in Dessau, Germany. Scheduled to start up in mid-2023, the plant will recycle composite packaging waste made of aluminum, plastic, and paper. The process will be further developed by refining technologies such as digital watermarking, eddy-current detection, and near-infrared detection to enable intelligent sorting of ABL packaging into an ABL packaging material stream. “With the construction of the first recycling plant for composite materials made of plastic, paper, and aluminum, we aim to produce high-quality, film-ready plastic recyclates for packaging applications while returning the recovered aluminum to the material cycle,” concluded Thorsten Hornung, managing director of Saperatec (8).

Members of the pharmaceutical value chain are looking beyond product development to meet sustainability goals. Schreiner MediPharm, for example, is a founding member of the Alliance to Zero, a non-profit partnership dedicated to enhancing sustainability throughout the pharmaceutical supply chain. Launched in June 2021 and based in Switzerland, the initiative is designed to support pharmaceutical and biotech companies in their transition to net-zero emissions in line with the Paris Climate Agreement (9).

The Alliance to Zero pursues the goal of launching net-zero pharmaceutical products in regulated markets by 2030 at the latest. To achieve this, the founding members have committed to developing a joint net-zero offering by 2026 to provide pharmaceutical companies with enough time to finalize their overall product on this basis.

The Alliance has developed a roadmap for a net-zero emissions concept for pharmaceutical production and the supply chain. Currently, necessary steps and a harmonized language are being developed, and principles are being defined for evaluating and monitoring the entire emissions footprint of pharmaceutical end products. In addition, the Alliance is planning to collaborate with academic and non-profit organizations pursuing similar goals.

Dr. Thomas Schweizer, president of Schreiner MediPharm, emphasized the importance of the company’s membership in the Alliance: “For Schreiner MediPharm, as a pioneer in the production of innovative functional labels, sustainability starts as early as in product development that considers all life cycles to achieve a reduced environmental footprint. For us, co-founding the Alliance to Zero means another important step toward holistic sustainability. We are convinced that, together with the other Alliance partners, we will be able to drive the development of net-zero pharmaceutical products.”

The Alliance to Zero encompasses component suppliers, machine manufacturers and assembly/manufacturing service providers, manufacturers of primary and secondary packaging, and companies responsible for final product assembly or handling products that have been returned after use. Other founding members include Dätwyler, Harro Höfliger, HealthBeacon, Körber Pharma, SCHOTT, Sharp, and Ypsomed. The close collaboration across traditional company boundaries, as well as the specialized expertise of each partner, will result in the development of holistic solutions that will move the pharmaceutical industry closer to net zero.

1. Shorr Packaging, “The 2022 Sustainable Packaging Consumer Report,” White Paper, July 20, 2022.

3. Keystone Folding Box, “Keystone Folding Box Co. Completes Multi-Million-Dollar Production Equipment Installation,” News Release, October 2022.

4. TekniPlex Healthcare, “At PACK EXPO, TekniPlex Healthcare to Debut World’s First Fully Transparent Recyclable Mid-Barrier Blister Package,” News Release, October 2022.

5. Avient, “Avient Debuts Next-Generation Solutions to Facilitate Use of Recycled Plastics in Packaging Applications,” News Release, June 16, 2022.

6. Schreiner MediPharm, “At PACK EXPO, Schreiner MediPharm to Debut Functional Labels Designed from More Sustainable Materials,” News Release, October 2022.

7. Hoffmann Neopac, “Neopac’s Polyfoil MMB Tube Approved by USA’s Association of Plastic Recyclers,” News Release, Jan. 30, 2022.

8. Hoffmann Neopac, “Closing the Loop with Aluminum Barrier Tubes,” News Release, Feb. 22, 2022.

9. Schreiner MediPharm, “For a Sustainable Pharma Supply Chain: Schreiner MediPharm Among Founding Members of ‘Alliance to Zero,’” News Release, Oct. 7, 2021. 

Hallie Forcinio is packaging editor for Pharmaceutical Technology. 

Pharmaceutical Technology
Volume 46, Number 11
November 2022

When referring to this article, please cite it as H. Forcinio, “Consumers Seek Sustainable Products,” Pharmaceutical Technology 46 (11) (2022).

Pharma companies set goals and adopt more sustainable alternatives.

Consumers Seek Sustainable Products

The closure market continues to expand. Worldwide demand for caps and closures is expected to grow at a 5.6% compound annual growth rate between 2022 and 2026, according to a report from Future Market Insights. Pharmaceutical applications will help spur that growth, particularly with the development of innovative child-resistant designs and more sustainable, often lighter weight, options (1).

When considering caps and closures for pharmaceutical products, manufacturers and contract packagers express concerns about container/closure integrity; product, patient, and caregiver safety; tamper evidence; child resistance; precise dispensing; and ease-of-use by consumers who lack dexterity and strength. In addition, any changes in cap/closure design or application equipment must integrate seamlessly on filling lines.

To provide tamper evidence and an indication of first-opening on syringes and vials at point-of-use, Schreiner MediPharm has developed label-based security concepts. For example, its Cap-Lock security label/cap adapter combination for luer-lock syringes features a plastic cap adapter placed on the primary closure of the syringe and interlinked with it to equalize the diameter differences of the syringe body and closure. Subsequently, a label is applied on conventional labeling equipment and wraps around the syringe body and cap adapter. “When a user opens the syringe cap, the label is partially destroyed, thus clearly and irreversibly indicating that the cap has been opened,” reports Gene Dul, president of Schreiner MediPharm US. “The utilization of Cap-Lock in daily healthcare settings is particularly easy and safe; the syringe can be opened as usual and, due to the larger diameter, the adapter is easier to twist off, even when wearing gloves,” he explains.

For vials, Schreiner MediPharm has developed a similar tamper-evident concept to help prevent illegal reuse of original containers. This security label wraps around the vial up to the level of the cap. Opening the vial requires the removal of an integrated tear strip. Any attempt to reseal the label leaves visible evidence. In addition, once the tear strip is removed, a warning message emerges and clearly indicates the vial has been opened. Optionally, a void effect can be added, featuring previously invisible lettering or symbols that separate from an indicator field. “Thus, it is obvious at first glance whether the product is an originally sealed medication,” says Dul. Unlike shrink-wrap solutions, no heat is applied, so the tamper-evident labels are compatible with heat-sensitive drugs. The highly customizable labels can be adapted to specific
applications and integrated with additional functionalities such as counterfeit protection, light (ultraviolet) barrier, or radio frequency identification chip for digital applications.

Tamper-evident protection extends to dropper bottles with a product line from Tekni-Plex Healthcare. The bottles range in capacity from 5 to 30 mL fitted with 0.03-, 0.04-, or 0.05-mL droppers and tamper-evident or child-resistant caps (2).

Selig Group combines tamper evidence with hermeticity in its TamperSeal induction seal liner. The two-piece Top Tab 2 TamperSeal induction seal eliminates the need to break through the liner with a potentially unclean tool or unwashed finger. This prevents contaminants from entering the package or transferring to residual lining material (3).

Selig also is working on a custom
dispensing liner, which combines an initial hermetic seal with dispensing control for solid dosage forms. “Currently consumers can get many doses when pouring from a 38- or 43-mm orifice, and then are challenged with getting these (now touched by hands) doses back into the container,” explains John Brown, vice-president, Marketing and Business Development at Selig Group. He explains, “If the FDA issues any advice for controlled dosage, similar to blister pack dispensing, we believe we have a solution that is easy to
commercialize with existing bottles, caps, and equipment.”

Cap/closure application equipment also must keep pace with new designs and other industry trends. Container/closure integrity depends on consistent torques within the correct tolerances. “This is especially important for induction-sealed products,” says Omar Azam, Eng., applications engineering manager at NJM, a ProMach product brand.

To ensure product quality, pharmaceutical manufacturers and contract packagers want feedback on every cap application. “They want to know how tightly each cap is closed,” reports Deborah Smook, vice-president of Marketing & Business Development at TurboFil Packaging Machines. “This is especially true for containers that could potentially leak, which could impact product efficacy as well as total delivered dosage,” she explains. To meet that need, TurboFil has developed the servo-driven Acrobat chuck capper, which records how tightly each cap is applied.

In addition to precision torque and torque data reporting, the servo-driven chuck capper provides gentle handling and minimizes the need for change parts. Servo motor operation controls torque accurately and repeatably regardless of container size.

The module’s two-chuck system features a “chasing chuck” that automatically locates the next bottle along the belt. The mobile, adjustable chasing chuck allows the belt itself to serve as a spacing tool. This proprietary technology and parallel belts eliminate the expense of making and storing change parts for all but the smallest bottles, which need only minor inexpensive parts.

For caps with difficult threads, the system can perform counterclockwise thread seating. Gentle handling is assured through positive placement and cap-specific stainless steel serrated pneumatic chucks. This differentiating combination eliminates erosion between the chuck and the cap ridges, mitigating the risk of generating particulates that can contaminate machine surfaces as well as bottle contents. “By contrast, simple spindle cappers drop caps onto bottles, frequently resulting in misfeeds, cross-threading, and rejects,” says Smook.

The Acrobat chuck capper can handle most cap styles and sizes up to three inches in diameter, including flat, port, hinged, child-resistant, continuous-thread, twist-top, metal-lug, tilt-top, and tamper-evident designs and accommodate bottle heights ranging from 1–12 inches and nearly any bottle shape—round, square, rectangular, oblong, and F-style. Ideal for lines running multiple bottle and cap sizes, the machine is available in single- and dual-head formats capable of processing up to 90 units per minute.

Other machines that are capable of consistent torques within required tolerances along with real-time torque adjustment, applied torque monitoring, and tracking capability, include NJM’s beltorque in-line capper family. Patented cap-to-container alignment incorporates precision-machined cap delivery change parts to eliminate cross-threads and rejects.The systems also offer patented non-slip and synchronized cap pre-tightening and final torquing belts that eliminate container damage or cap scuffing even under the most demanding torque applications.

As cap/closure designs continue to evolve, Azam expects closures will offer easier opening and dispensing along with improved child-resistant and tamper-evident performance. Dul agrees, predicting, “Sophisticated label-based security concepts combining analog and digital tamper evidence will contribute to enhanced container integrity. The ultimate goal is supporting product and patient safety while ensuring smooth processability in pharma production.”

“We also believe that ‘controlled dosage’ will again be considered by the federal government as a way to discourage overdosing either accidentally or purposefully, including accidental child ingestion,” says Brown. In addition, there will be growing awareness of environmental impact. “Sustainability has not been completely adopted by brand owners yet as these [pharma] packages are not typically used outside of the home and are not becoming an eyesore on beaches, parks, ocean plastics, etc.,” he concludes.

Future Market Insights, “Caps and Closures Market Is Set to Expand at a CAGR of 5.6% & to Reach US$ 141 Bn During 2021 to 2031,” Press Release, July 26, 2022.

Tekni-Plex Healthcare, “At Pharmapack Paris, TekniPlex Healthcare to Showcase Robust Range of Drug Delivery Solutions,” Press Release, June 28, 2022.

SeligGroup, “TamperSeal,” TamperSeal - Selig Liners (seligsealing.com), accessed Aug. 1, 2022.

Hallie Forcinio is manufacturing editor for 

Product safety and security are paramount when it comes to container closures. 

Closure Options Expand

The pharmaceutical industry registered $800 million in sales in 2020 and is forecast to grow at a 7.6% compound annual growth rate (CAGR) through 2026, according to 

Pharmaceutical Manufacturing Trends Shaping the Future

, a whitepaper published in March 2022 by PMMI Business Intelligence, a division of PMMI, The Association for Packaging and Processing Technologies.

The pharmaceutical industry must keep pace with changing product formats and production preferences and overcome supply chain constraints. The shift toward higher-value injectables and customized runs for personalized medicine is driving the expanded use of contractors, while also pushing manufacturers toward more automated production lines (1).

The global pharmaceutical contract packaging is expected to grow at an even stronger pace than the industry overall with an 8.1% CAGR through 2027 to reach a value of $29.62 billion. These firms handle primary packaging and labeling and also provide secondary services, such as assembling and secondary packaging of vials, auto-injectors, and prefilled syringes. Forces driving usage of contract packaging service providers include a lack of in-house expertise and infrastructure and budget constraints. Contract packagers also can offer advantages such as the ability to accommodate multiple packaging formats, operate highly sophisticated facilities, and provide expert counsel regarding regulatory requirements (2).

Both contract packagers and in-house lines are moving toward higher levels of automation to address needs for higher throughput and offset labor shortages. This is translating into increased use of robotics, deployment of artificial intelligence, and implementation of turnkey systems (3).

According to the PMMI report, the most popular machine investment is in cartoning equipment, followed by bottling, palletizing, closing, filling/dosing, and labeling/decorating/coding systems. Meanwhile, pharmaceutical manufacturers want machines with features such as flexible/faster changeover, robotic control, and vision inspection. These organizations also want cleanability, easier maintenance, better preventative/predictive maintenance capabilities, and improved operator safety (3).

In addition, the pace of digitization is accelerating to meet regulatory requirements, particularly those related to the Drug Supply Chain Security Act and False Medicines Directive. Digitization also can help address cybersecurity concerns, achieve operational visibility, and support blockchain product tracking (3).

Another influence is the steady growth in the direct-to-consumer e-commerce channel, which is boosting the need for packaging safety, product integrity, and comprehensive labeling. Sustainability continues to receive attention. Consumers prefer sustainable products and packaging. To meet sustainability objectives, 67% of pharmaceutical manufacturers are lightweighting packaging, 53% are increasing post-consumer-recycled content, 47% are seeking more energy-efficient equipment, and 40% are changing packaging formats (3).

COVID-19 supply chain challenges have created shortages and delivery delays in packaging materials, raw materials, equipment, and parts. These delays and shortages have postponed both product launches and operational improvements. As a result, pharmaceutical manufacturers are seeking closer collaboration and cooperation with OEMs and suppliers of packaging and raw materials. To achieve this goal, pharmaceutical manufacturers want OEMs and suppliers to offer aftermarket service/support, integrate new machines, enhance equipment accuracy and reliability, simplify changeover, maximize machine flexibility, deliver parts quickly, and provide support for concept models to visualize equipment as well as for Installation Qualification and Operational Qualification (1).

1. PMMI, The Association for Packaging and Processing Technologies, “Pharmaceutical Industry Increases Automation, Digitization,” Press Release, Aug. 15, 2022

2. Research and Markets, “Global Pharmaceutical Contract Packaging Market Report (2022 to 2027) - Industry Trends, Share, Size, Growth, Opportunity, and Forecasts,” Press Release, June 7, 2022.

3. PMMI, The Association for Packaging and Processing Technologies, “Pharmaceutical Manufacturing, the Future Ahead,” Infographic, Aug. 15, 2022.

Rapidly growing industry must overcome supply chain constraints. 

Forecast Looks Good for 2023

Parenteral packaging, solid dose packaging, and quality control innovations were highlighted at INTERPHEX 2022 (May 24–26, 2022, at Javits Center in New York, NY). Among quality control innovations, NJM, a ProMach product brand, introduced its integrated CMD metal detection system for pharmaceutical and nutraceutical bottles. The system integrates a metal detector head from a top-tier vendor such as Thermo-Scientific, Mettler-Toledo, or Loma with a raised-bed conveyor to smooth bottle handling and eliminate the need for bottle transfers.

Ideal for tablets, capsules, powders, and liquid products, the system can handle round, oval, square, and rectangular bottles made of plastic or glass from 1.5 to 7.9 inches (38 to 200 mm) in height and from 0.6 to 5.5 inches (16 to 140 mm) in diameter. The CMD system can be equipped with a separating wheel, starwheel, or feedscrew spacing device, depending on the bottle shapes and sizes being handled. With a length as short as 42 inches (1067 mm), it easily fits downstream of the cottoner or upstream of the capper.

The CMD system has been engineered to optimize cleanliness and cleaning processes and can be equipped with optional reject and reject verification systems. Featuring an open frame and removable top and bottom conveyor chain wear strips, this cGMP-compliant system simplifies line clearance, cleaning, and inspection by eliminating tablet entrapment zones and exposed wires. Package changeovers require no tools (1).

Marchesini Group USA showcased its Compact-24 monoblock filler/capper. A magnetic transport system autonomously positions, groups, and moves each bottle individually, simplifies changeover, and efficiently handles small and medium batches. The counting section consists of two 12-channel counting groups. For low counts, a twin-flap function can divide each group into six-plus-six channels. A six-head, continuous-motion rotary capper completes the system. A plug-and-play drop chute expedites changeover. Onboard cameras control product shape, size, and color and track each dose to ensure accurate counting. The monoblock can be equipped with cotton and desiccant feeders as well as 100% product weight inspection (2).

An RNFM robotic nest filling machine from Steriline enhances quality, efficiency, safety, and flexibility for aseptic fill/finish operations by reducing the need for human intervention and the potential for operator-related mistakes. Special sensors detect the type and capacity of the containers, and the machine software automatically adapts the process according to recipes in the database. Sensors also can identify and promptly manage any non-compliant pieceswithout operator intervention, thus, reducing waste and downtime. The fill/finish system is compatible with vials, cartridges, and syringes and can be equipped with an open or closed restricted access barrier or isolator barrier system (3).

For high-speed vial labeling, MG America offers the WL-1-RT wraparound labeler. A trunnion transport system positively controls vials to enable precise label application at speeds up to 600/min. The unit can be equipped with thermal-transfer and laser-coding printers and is preconfigured for the integration of an OCR/OCV vision inspection system. Non-conforming labels are rejected before application, and infeed/outfeed bi-flow tables provide optimal buffering (4).

In other parenteral packaging news, West Pharmaceutical Services won an INTERPEHX Exhibitor Award for Biotech Innovation for its DeltaCube modeling platform. The DeltaCube analytics tool helps manufacturers select and optimize container/closure systems earlier in the development process by guiding the selection of vial, stopper, and seal combinations based on fit. The tool also supports troubleshooting of defects or container/closure integrity failures due to dimensional issues (5).

Price is an essential consideration when purchasing a packaging machine, but failure to consider total cost of ownership (TCO) could result in a line that generates higher expenses over its life span. Calculating TCO considers many factors. A guide from BW Packaging Systems, 

Calculating Total Cost of Ownership (TCO) for Packaging Lines and Machinery

, helps manufacturers and co-packers quantify optimum machine choices. In addition to defining 10 cost factors to consider, the guide provides advice for keeping costs low, offers tips from packaging industry experts, and provides links to helpful resources (6).

1. NJM, “NJM Introduces Integrated CMD Metal Detection Systems,” Press Release, Feb. 8, 2022.

3. Steriline, “INTERPHEX 2022: Steriline Robotic Applications to Improve Quality in Drug Primary Packaging,” Press Release, May 24, 2022.

4. Dale, Christopher, “Booth Appointments at Interphex? Email, May 5, 2022.

5. West Pharmaceutical Services, “West Receives Exhibitor Award for INTERPHEX 2022 for Proprietary DeltaCube Modeling Platform,” Press Release, May 24, 2022.

6. BW Packaging Systems, “Calculating Total Cost of Ownership (TCO) for Packaging Lines and Machinery,” White Paper,

Packaging Machine Costs | BW Packaging Systems

Exhibitors display innovations for parenteral and solid dose products. 

INTERPHEX 2022 Highlights Packaging and QC 

The intense pressure to develop vaccines and treatments for COVID-19 has helped spur strong growth in the pre-filled syringe market and innovations in syringes and syringe fill/finish operations. “Pre-filled syringes reduce the number of steps for injection, lower the risk of injury and cross-contamination, and offer higher dose accuracy,” explains Silvia Gallina, Syringes Platform Product Management at Stevanato Group.

“Pre-filled syringes are now a widely accepted part of the drug life-cycle and are often considered as early as Phase II in the drug development process,” reports Michelle Deutsch, head of Global Product Management at SCHOTT Pharmaceutical Systems. She adds, “The need for differentiation and the move to homecare continue to be critical drivers of this evolution. New drugs enabling technologies at different stages of development are also beginning to open up new possibilities for pre-filled syringes as it becomes possible to deliver higher fill volumes and higher viscosity drugs as subcutaneous injections.”

As the market for pre-filled syringes expands, attention is being devoted to glass improvements, reducing glass-to-glass and glass-to-metal contact, using cameras and other inspection tools to maximize syringe quality, designing products applicable to autoinjectors, and addressing the needs of sensitive biologics.

“Biologics tend to have high chemical sensitivity, low stability, and high viscosity,” says Gallina. For biologics, control of silicone and tungsten levels is key to minimizing or eliminating particulates, extractables, and leachables. Stevanato Group offers two product lines for biologics, the SG Alba and SG Nexa platforms, and is organizing production so it can provide these syringes anywhere in the world. Both product lines have been developed to reduce risks when a sensitive drug product contacts the containers. “SG Nexa platform features an optimized silicone layer, maximum cosmetic quality, tight dimensional tolerances, and compatibility with autoinjectors on the market,” reports Enrico Barichello,Alba Platform product manager at Stevanato Group. “SG Alba platform offers similar characteristics but has been designed for improved integrity of the lubricant layer, reducing subvisible particles and providing a better functionality when integrated in a device, particularly for drugs that may be very sensitive to silicone oil.”

SCHOTT’s syriQ BioPure prefillable syringes offer minimum levels of tungsten and low or no silicone. “While most approaches to managing this risk are based on immobilizing the silicone layer, syriQ BioPure silicone-free offers an alternative system that uses no silicone, relying instead on tight dimensional specifications and superior hydrolytic resistance,” says Deutsch. Available in 1- and 2.25-mL sizes, the syriQ BioPure syringes meet dimensional tolerances that exceed ISO requirements.

Another glass syringe innovation, a flat-shoulder syringe from Gerresheimer, minimizes or eliminates residual volume, an important characteristic for extremely costly drugs. As storage temperatures have dropped, the bar has risen for glass pre-filled syringes. Deutsch explains, “[Messenger RNA] mRNA—at least for now—has changed the game. Some vaccines had required transport at -4 °C, but today, many customers want to see proof of much deeper cold temperature performance. These requirements are shaping a new kind of pre-filled syringe demand. In some cases, pre-filled syringes made of cyclic olefin copolymer (COC) are a suitable alternative to glass pre-filled syringes.”

Break-resistant and lightweight, COC offers a glass-like appearance and performance and better product stability and shelf-life. One company that has begun to adopt COC syringes is Nephron Pharmaceuticals. The 503B outsourcing operation and producer of generic products has introduced a 50-mL COC syringe, which is filled on automated equipment and is compatible with highly viscous drugs. A disconnected plunger simplifies storage. The first Nephron product to use the COC syringe is 8.4% sodium bicarbonate injection (USP 4.2 mg/50 mL) (1). Sodium bicarbonate is used in emergencies to regulate or increase a patient’s pH levels, and the COC syringe gives it a 365-day beyond-use date. Nephron plans to offer a variety of products in the COC syringe with the next launch scheduled to be 50% dextrose injection. Eventually, the 50-mL COC syringe will be joined by 5 mL, 10 mL, and other sizes.

For biologics that need an autoinjector, BD Medical–Pharma Systems has been developing an addition to its Intevia product line. The Intevia 2.25-mL disposable autoinjector is designed to dose accurately, operate easily and consistently, and minimize injection pain. The two-step, push-on-skin device integrates an autoinjector with a Neopak XtraFlow 2.25-mL glass pre-fillable syringe (2). To accommodate viscosities up to 40 cP and a range of injection volumes, the syringe may be equipped with a 29G Thin Wall, 27G Special Thin Wall, or 27G Ultra Thin Wall needle, which is hidden and protected. When in use, a large inspection window and plunger rod show injection progression. The unit also provides visual and audible feedback indicators (3).

Non-traditional pre-filled syringe options

As the demand for injectables grows, non-traditional options are evolving such as pre-filled blow-fill-seal (BFS) syringes based on technology from ApiJect Systems. To support use of the technology, ApiJect has established a Technology Development Center near Orlando, FL. Plans call for doubling the footprint of the facility to 32,000 square feet and adding two BFS machines by mid-2023 (4). “This new facility is devoted to working with pharmaceutical and biotech companies to design, engineer and test how to fill and finish their injectable drug products in a new type of scalable, single-dose, pre-filled injector that is made using the ApiJect Platform,” reports Jay Walker, chairman and CEO at ApiJect. He explains, “By bringing together the high-speed, high-volume BFS manufacturing process with attachable components, including needle hubs, the ApiJect Platform is designed to make it possible for more injectable medicines and vaccines to efficiently be filled and delivered to patients in a pre-filled injection device. This facility provides capabilities to shorten supply chains and bring the development of critical injection device technologies back to the United States.”

Prevention of needlestick injuries and misdosing is another area of concern and development activity. The Innosafe syringe from Gerresheimer features an integrated safety device and is supplied in a standard tub and nest configuration, so it can run on existing filling lines without any significant line adaptations.

Nemera has expanded its Safe’n’Sound pre-filled syringe accessory lineup with the addition of a 2.25-mL size. Originally introduced for 1-mL, the passive Safe’n’Sound device prevents needlestick injuries. Compatible with low fill volumes and high viscosities, a large thumb pad enhances usage, and a rounded shape offers a larger labeling surface. Clear tip visibility simplifies drug inspection (5). The safety syringes can be assembled on Harro Höfliger Assembly Lab equipment. The semiautomatic machine quickly switches between 1- and 2-mL sizes and can be changed over in a few minutes to handle other devices such as pens or autoinjectors (6).

Protecting patients against painful or incorrectly performed injections is the goal behind the Luer Adapter Fixation concept from Schreiner MediPharm. It reduces the risk of incorrect or incomplete hypodermic needle screw-ins during a syringe’s insertion with a luer adapter (7). It’s particularly well-suited for medicines administered in emergency settings where hectic situations might cause application errors. “In the case of cosmetic medicine, the new adapter concept can help avoid needle pop-off—especially when injecting highly viscous hyaluronic acid, which requires higher exertion of force and pressure,” reports Gene Dul, president of Schreiner MediPharm US.

Developed specifically for glass syringes, the Luer Adaptor Fixation device and label are applied to the syringe during the secondary packaging process. “The plastic ring would be pushed onto the luer adapter of the pre-filled syringe and interlocked with it to equalize the different radii of the adapter and syringe body. The plastic ring and syringe body would then be connected by means of a label to fix the luer adapter in place,” explains Dul. The extended label area offers ample space for additional product information. The design is customized for each application (syringe size, etc.) and the user’s packaging process is evaluated to ensure there’s no impact on container/closure integrity (7). The Luer Adapter Fixation concept can replace shrink labels and avoid heat exposure to temperature-sensitive biotech drugs.

Another pre-filled syringe innovation from Schreiner MediPharm, the Cap-Lock security concept, combines a cap adapter and label. The label wraps around the syringe body and cap adapter. An integrated perforation provides irreversible tamper evidence. “This helps ensure the integrity of the container and prevents its undetected opening,” says Dul. This gives “pharmaceutical manufacturers ... a customized and validated full-service solution for equipping luer-lock syringes with reliable tamper evidence,” says Dul.

Better inventory management is the goal behind syringes equipped with radio frequency identification (RFID) tag-equipped labels. Kit Check technology from Fagron Sterile Services embeds a microchip in the label of ready-to-administer operating room syringes, enables accurate tracking and inventory records, and ensures the right drugs are available when needed (8).

With rising demand from oral, injectable, and veterinary products, the market for syringe fill/finish equipment has expanded significantly since 2019. Deborah Smook, vice-president of Marketing and Business Development for TurboFil Packaging Machines, attributes this growth to the ease of use and dosing accuracy the format can provide. She explains, “Precision dosing is increasingly important as some solutions require exact amounts to be optimally effective. Pre-filled syringes limit point of administration dosing errors either by healthcare personnel or patients themselves.”

She adds, “More specific to the syringes sector, though, are issues regarding regulatory foresight. By this, we mean that the pathway to final product approval isn’t always immediately evident. This is largely because the [equipment] solutions we provide are highly customized and therefore might require individualized guidelines.”

Equipment is becoming more automated and flexible. The push toward automation is driven by manpower shortages and labor costs, and flexibility is demonstrated by a syringe barrel feed system from Shibuya Hoppmann. It can handle six barrel sizes and two tip styles. Feeding and orienting occur at 80 parts/min.

Flexibility is built into benchtop machines capable of handling syringes, cartridges, or vials. Designed to address lab, clinical trial, personalized medicine, and other low-volume needs, the four Labworx machines from Groninger fill with a peristaltic pump, fill with a rotary piston pump, stopper, or crimp. The semiautomatic units feature a laminar-
flow-friendly design, two-button operation, wireless control via tablet or smartphone, and automated batch records (9).

To ensure parenteral products are safe, quality control is essential in product development and production and highly regulated. Data integrity also is required and an area of weakness that often prompts warnings from regulators. A growing role is being played by robotics, which can provide the material handling needed to perform 100% inspection.

Interest in 100% inspection has been given impetus by United States Pharmacopeia (USP) <1207> Package Integrity Evaluation–Sterile Products (10). While USP <1207> is not a requirement, Oliver Stauffer, president of PTI–Packaging Technologies & Inspection, says, “USP <1207> uses strong language and lays out very fundamental principles for container/closure integrity testing (CCIT) … [and] makes a clear case for adopting deterministic methods.” As a result, parenteral packaging operations are shifting to more accurate and reliable CCIT methods. “For pre-filled syringes,” he says, “operations are using methods like helium tracer gas to determine container component seal performance in the design phase, deploying high-voltage leak detection in the production setting, and using vacuum decay to qualify assembled autoinjectors.”

To prevent future regulatory complications, regulatory filings must focus on the science of the test methodology rather than the technology. Stauffer explains, “If a regulatory filing properly identifies scientific reasoning behind the application and lays a foundation for the method deployed, the science and the method are what shall remain constant within the filing. If a filing does not focus on the science and applies a stronger focus on the technology or even the equipment used, the filing is not adaptable to the changing technology landscape. … The scientific fundamentals of a method provide quality, while technology is simply the tool to achieve it.”

With supply chain issues a constant concern, all suppliers of syringes and fill/finish equipment are taking action to prevent delays and shortages. Machine builders have expanded inventories, particularly for electronic components. At TurboFil, “Warehousing certain electronic components, including programmable logic controllers … has limited the adverse impact,” reports Smook.

On the syringe side, Stefan Verheyden, global vice-president Gerresheimer Biological Solutions, reports, “We have done everything needed to secure tubing and component supply while in parallel, we have been, and still are, investing heavily in ready-to-fill capacity expansion on a global level.”

Stevanato Group has taken steps to mitigate supply chain issues and is working closely with suppliers and customers, increasing capacity in its plants and continuing to expand operations. A new plant in Indiana is expected to start production in 2023, and a new plant in China is planned.

Like its counterparts, SCHOTT is boosting operations worldwide with an expansion in St. Gallen and a new facility in Hungary. As a vertically integrated company, SCHOTT produces its own glass tubing but must source other materials and components. To improve sourcing security for components such as syriQ Rigid Cap closures and needles, the company has implemented continuous improvement programs that couple design improvements with supply risk mitigation. Other steps being taken to prevent supply chain snafus include “identifying areas where we can become more self-reliant, standardizing components, and broadening our sources of supply,” says Deutsch. Another tactic, the FastTrack program, maintains minimum stocks in inventory. “With this program, we target a two-week order-to-shipping lead time window,” concludes Deutsch.

SCHOTT also recently announced a substantial investment in a new manufacturing facility in Müllheim, Germany, which will produce prefillable COC syringes. “Our validated polymer syringe systems meet the demanding requirements of new drug categories, including ultra-low temperature storage applications needed for mRNA-based applications,” said Mario Haas, vice-president for the Polymer Solutions division of SCHOTT’s Pharma business unit (11).

Nephron Pharmaceuticals, “Nephron Launches New Syringe Presentation,” Press Release, Jan. 26, 2022.

K. Yadi and L. Maritan, “Innovating in the Viscosity Design Space for Handheld Combination Products: A New 2.25 mL Autoinjector Platform,” ONdrugDelivery 117 pp 40-44 (March 2021).

BD, “BD Solutions for Enabling Delivery of Complex Biologics BD Intevia 2.25 mL Disposable Autoinjector,” Product Sheet, 2021.

ApiJect Systems, “ApiJect Systems Announces the Opening of the ApiJect Technology Development Center in Greater Orlando, FL,” Press Release, April 13, 2022.

Nemera, “Safe’n’Sound 2.25 mL,” Safe’n’Sound 2.25 ml | Passive safety systems for PFS | Nemera, accessed May 4, 2022.

Nemera, Harro Höfliger, “Premium Passive Safety Device,” reference_sheet_nemera_HH.pdf, accessed May 4, 2022.

Schreiner MediPharm, “Schreiner MediPharm Develops Fixation Aid for Ease and Safety of Luer Adapter Handling,” Press Release, Nov. 30, 2021.

Fagron Sterile Services US, “Product Innovation at Fagron Sterile Services US Drives Job Growth and Investment,” Press Release, Mar. 15, 2022.

Groninger, “Labworx Series, Benchtop Machine Portfolio,” Brochure, 2021.

The United States Pharmacopeial Convention, “United States Pharmacopeia <1207> Package Integrity Evaluation–Sterile Products.”

SCHOTT, “Boost for Drug Delivery Systems: SCHOTT Inaugurates Plant for Prefillable Polymer Syringes at New Facility in Germany,” Press Release, May 6, 2022.

Vol. 46, No. 7 
July 2022 
Pages: 38­-43

When referring to this article, please cite it as. H. Forcinio, “Pre-filled Syringes Show Strong Growth,” 

Demand spurs innovations in syringes and syringe fill/finish operations. 