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

Hallie Forcinio

Pharmaceutical manufacturers strive to address many concerns including cost and lead times in the supply chain. “Speed to market remains a top priority with our clients,” says Kristin Smith, client coordinator at Sharp. Other concerns include compliance with stringent quality control requirements and delivering on sustainability commitments.

Outsourcing operations, especially packaging, addresses these priorities and generates many benefits for pharmaceutical manufacturers. As a result, 60% of pharma manufacturers outsource at least a portion of their operations to a third-party contractor, according to 

2022 Pharmaceutical Manufacturing: Trends Shaping the Future

, a report published in March 2022 by PMMI Business Intelligence, a division of PMMI, The Association for Packaging and Processing Technologies. Driving forces behind the interest in outsourcing include the rise of injectables and personalized medicine and the accelerated pace of new product development, which has strained production capabilities for pharmaceutical manufacturers (1).

Packaging is often outsourced because of its complexity. Smith at Sharp explains, “Packaging involves a degree of technical, operational/process, and design complexity, which creates the need for ‘solutions’ providers … to manage packaging as a holistic process including design, engineering, packing, serialization and aggregation, foreign-trade zone, qualified person services and release, stability, and ID testing.” In addition, outsourcing can provide “a partner who can offer a breadth of regulatory and rapid launch requirements, including global regulatory requirements for multi-market launches.”

Contract packaging services provide numerous advantages for both clinical trials and commercial medicines. Contract packagers “can offer expertise, flexibility, and efficiency, while further mitigating risk and maintaining product quality and safety,” says Justin Schroeder, global vice-president of technical sales at PCI Pharma Services.

For example, “using a contract development and manufacturing organization (CDMO) allows companies to benefit from the expertise and specialized knowledge gained through handling a wide variety of products with varying parameters, such as ultra-low temperature handling,” says Harry Lindenmuth, vice-president operations at Almac Pharma Services, who oversees the company’s Audubon, Pennsylvania, site.

Smith at Sharp agrees, noting third parties often are chosen for therapies that require more complex handling, assembly, packaging, and storage requirements (e.g., cold chain, frozen storage, or high-value small-batch drugs). In addition, contract packaging organizations maintain a broad network of suppliers, including those who will collaborate on sustainable packaging efforts.

Reduced costs are a major benefit of outsourcing because manufacturers don’t need to purchase, install, and validate new equipment and lines, thereby freeing up capital and personnel for use elsewhere in the operation (1). Eliminating the need to invest in packaging equipment, labor, materials, and floorspace allows pharma and biotech companies to focus on their core competencies (drug development and manufacturing). This not only lowers costs but “also provides greater flexibility and scalability, enabling them to grow quickly and adapt easily to changes in demand,” says Lindenmuth. The outcome is improved supply chain efficiency and inventory management and reduced lead times.

Josh Goolcharan, director of sales and marketing at Reed-Lane, agrees, noting, not only are packaging activities outsourced but these partners are asked to manage the procurement of all necessary components. He says, “This allows customers to focus efforts more on marketing existing products and developing additional ones.”

Speed to market may be the biggest benefit of outsourcing pharmaceutical packaging. Outsourcing can deliver rapid launch support and/or launches in multiple markets across the globe and reduce risks by providing a deep understanding of up-to-date regulatory and compliance guidelines in multiple countries.

Outsourcing also can strengthen the supply chain and provide production redundancy. “Single sourcing is no longer a viable strategy when material and labor shortages persist in many countries,” explains Schroeder. He adds, “PCI and other CDMOs are organized and structured with flexible assets complemented by a network of locations around the globe to move quickly and operate with agility. [Service providers can also] increase speed by serving in a consultative advisory capacity, helping clients streamline their approach and avoid unnecessary steps.”

Engaging an experienced CDMO expands packaging options and enhances quality and efficiency because it provides access to knowledgeable teams, who routinely handle various types of pharmaceutical packaging. “Companies are provided with the surety that their packaging is performed correctly and consistently, and that processes, such as serialization, are performed to the highest level of compliance,” says Lindenmuth.

In short, “the right contract packaging organization can offer the experience, expertise, and technology to handle various packaging complexities,” says Smith. Wide-ranging expertise includes:

technical expertise, which accommodates a range of formats and environments such as precise vial labeling, assembly of pre-filled syringes and autoinjectors/pens, cold-chain/frozen storage, and protection for products with light/temperature/humidity sensitivities

operational expertise, which addresses speed-to-market requirements, strict quality control needs, and process efficiencies for multi-country launches, as well as scalability for growing or fluctuating volumes

design expertise, which balances functional and aesthetic design that addresses safety, end-user instructions, product sensitivities (light, temperature, humidity), and tracking and anticounterfeiting requirements.

Whatever services are provided, the manufacturer and CDMO must forge a collaborative relationship. Fully understanding the product, patients, and target markets ensures all criteria are met and the product reaches the patient on time and in the optimal format.

To meet rising demand, service providers are expanding their capabilities. For example, PCI Pharma Services has added new facilities in Bedford, New Hampshire; Bridgewater, Massachusetts; and Rockford, Illinois; to serve customers in key geographies. These expanded capabilities, which include innovative packaging and manufacturing methods, have been implemented in recognition of the need to get treatments to patients quicker than before, emphasizes Schroeder.

The company also has invested in software and expanded service offerings. Its pci | bridge digital supply chain management platform provides customers with a direct look into their systems and network of locations. “This digital supply chain management platform … gives clients access to real-time updates and information like production and order management status, inventory, batch release, global distribution, and invoicing,” says Schroeder.

PCI’s new consultative offering, SpeedSolutions, complements core manufacturing, clinical trial, and commercial packaging services. “SpeedSolutions allows PCI to shape and guide successful outcomes … by accelerating client molecules across the various phases of drug formulation and process development, analytical development, clinical trials, and ultimately, global commercial supplies,” reports Schroeder.

From its European Centre of Excellence, Almac Pharma Services offers specialized ultra-low temperature packaging that enables advanced, lifesaving medication to be packaged, labeled, and distributed in temperatures between -20 ºC and -80 ºC. “Our team works closely with clients to define … a tailored, robust, and commercially scalable process which takes into consideration the temperature requirements, allowable time out-of-condition, conditioning time requirements, final pack-out configuration, level of serialization aggregation required, temperature-controlled distribution, and global supply chain needs,” says Lindenmuth. With this capability, the CDMO has “processed and QP [qualified person]-released over 1000 batches, enabling them to be transported direct to the patient within as little as 20 hours.”

Almac Pharma Services also has invested in stick pack and sachet capabilities across all of its facilities. Installation of a triple-head dosing module has boosted capacity. “This key investment was in response to the increased demand from our clients in commercial packaging for pediatric formulations such as powders, granules, and mini-tablets,” reports Lindenmuth. Specialized packaging such as stick packs and sachets enables accurate dosing of drug products by offering pre-measured amounts, reducing over- or underdosing, and providing increased portability and convenience for patients. Sachets also can be customized with printed instructions and branding.

At Sharp, investments are focused on secondary packaging services for injectables and gene therapy. For gene therapy products, which typically involve small volumes and requirements for time- and temperature-sensitive handling, a dedicated 1000 ft2 packaging suite at its facility in Bethlehem, Pennsylvania, includes dedicated high-efficiency particulate air-filtering systems with full redundancy and an emergency power generator. Two ante-rooms at entry maintain positive pressure to ensure the cleanliness of the suite. An automated system constantly monitors temperature, humidity, and dew points and sends emergency alerts if a deviation occurs. Dedicated -80 ºC freezers also are monitored 24/7 (2).

Although Sharp specializes in secondary packaging for injectable formats, it also can provide isolator-based sterile filling and lyophilization services via its 25% stake in Berkshire Sterile Manufacturing. Semi-automated and automated, isolator-based filling lines offer the flexibility to handle syringes, cartridges, vials (either ready-to-use or bulk), and lyophilized products. On the fully automated line, robotics and multiple vision systems minimize the need for intervention by human operators (3).

Goolcharan concludes, as packaging experts, contract packagers offer cost-effective processes, the flexibility to address low- and high-volume requirements, and familiarity with multiple packaging styles (e.g., vials, pouching, bottles, blisters, carding, secondary operations, and kitting).

PMMI Business Intelligence, a division of PMMI, The Association for Packaging and Processing Technologies. 

Sharp Services. Supporting Commercial Gene Therapies–Transforming to Patient-Led Demand Model. SharpServices.com, accessed April 24, 2023.

Sharp Services. Creating Flexibility and Efficiency in Isolator-Based Filling with Robotics and Automation. SharpServices.com, accessed April 24, 2023.

When referring to this article, please cite it as Forcinio, H. Generating Benefits with Outsourced Packaging. 

Articles

Third-party contract packaging service providers can help save time and money. 

Generating Benefits with Outsourced Packaging

Whatever your product – parenteral, solid dose, inhalable, liquid, transdermal – you will find packaging innovations at INTERPHEX 2023 (April 25-27, Javits Center, New York, NY). Quality control is always strongly represented, but labelers, containers, filling lines, and systems that support traceability and sustainability also will be displayed across the show floor.

A high-speed x-ray inspection system checks pharmaceutical blister packs and pouches at speeds up to 400 ft (120 m)/min. The compact X34C x-ray inspection system from METTLER TOLEDO Product Inspection measures only 28 in (700 mm) long to occupy minimal space and simplify integration on the line. A checkweigher and combination checkweigher vision system also will be demonstrated. The Starweigh checkweigher checks the weight of small, unstable, lightweight products at up to 300 parts/min with accuracies of +/- 5 mg. The integrated CV35 checkweigher/vision system features a compact footprint, detects over- and under-filled products, and performs side, top, and bottom inspection (1).

Another inspection system, the Visual Rotating Inspection (VRI)series from Antares Vision Group, confirms closure integrity at rates up to 600/min using high-voltage, vacuum, and headspace gas analysis. It also detects cosmetic defects and particles and checks fill level. The VRI unit can inspect liquids in viscosities ranging from water-like to oily, suspension, gel, and emulsion. The system also checks crimping quality, flip-off color, neck-shoulder sidewalls, and stopper position. Optional add-on features include code verification, optical character recognition/optical character verification, and serialization (2).

A serialization-readycombination system from Wipotec integrates three functions: traceability, checkweighing, and tamper evidence/anticounterfeiting. The TQS-HC-A-TE machine offers precision weight monitoring, tamper-evident labeling, and serialization support such as in-line printing of batch or unique product identifiers, print verification, and the ability to add sensory data to a product’s unique identifier. Tamper-evident labeling systems seal folding cartons or apply additional anticounterfeiting vignettes (3).

Automated line clearance software, powered by artificial intelligence (AI), will be introduced on a machine from Marchesini Group. The system, developed by SEA Vision Group and ARGO Vision, relies on AI algorithms along with cameras and sensors to automate line clearance. Digitizing the clearing and cleaning phases and automating the checking phase prevents errors, reduces downtime, boosts product safety, and increases the line’s overall equipment effectiveness. Part of the Industry 4.0 software suite yudoo, smart clearance technology AI algorithms analyze the inspected scenes in-depth and in real-time, immediately identifying any mispositioned machine parts, foreign objects, or products passing through the unit (5).

SEA Vision also will demonstrate vision hardware and software combinations to inspect injectables. ChecKIT360 and ChecKITassembly kits can be installed on any vial or syringe filling and capping machine, as well as on syringe assembly machines. The systems can check for vial crimping defects, flip-off presence and color, stopper/cap presence and position, correct syringe assembly, and syringe label presence (4).

BellatRx has introduced the Notaris Plus pressure-sensitive labeler. The all-servo machine offers 100% speed-synchronized labeling, fast changeover, and ease of use. Capable of labeling up to 100 containers/min, the unit features integrated lot code and expiration date printing and visual inspection of labels and printing. A serialization package is available for track and trace requirements (5).

NJM, a ProMach product brand, plans to display its Courser 230 labeler. It can be configured to handle an array of containers including vials, syringes, bottles, ampules, cartridges, centrifuge tubes, auto-injectors, and other small or unstable packages. Design features include a trunnion starwheel for positive handling and a vertical label spool dispenser, which improves ergonomics and labeling accuracy. An optional thermal-transfer or laser printer can be installed to print variable data, including serialized data, on pre-printed or blank labels before application. Other options include a print inspection system, a label removal system that ensures incorrectly printed labels are reconciled on a separate web, and a label placement inspection system that identifies packages with missing labels and triggers a downstream reject device (6).

Sustainability is one of the topics at the INTERPHEX Technical Theater. The session, Sustainability Packaging and Contemporary Cartoner Design, is sponsored by Rotzinger Pharmapack.

1. METTLER TOLEDO Product Inspection. METTLER TOLEDO to Demonstrate Its Product Inspection Systems at Interphex 2023. Press Release. March 28, 2023.

2. Antares Vision Group. Antares Vision Group to Showcase Automatic Inspection Machine for Liquids in Glass Containers. Press Release. March 24, 2023.

3. Wipotec. At INTERPHEX, Wipotec to Showcase 3-in-1 System with Traceability, Tamper-Evident & Checkweigher Functionality. Press Release. March 24, 2023.

Smart Clearance Technology for the First Time in the US. Press Release. March 14, 2023.

5. BellatRx. Introducing Notaris Plus Labeler. E-Newsletter. March 2023.

6. NJM, a ProMach product brand. NJM Introduces the Enhanced Courser 230 Vial/Syringe Labeler. Press Release. Jan. 29, 2020.

7. INTERPHEX. Presenting the INTERPHEX Technical Theater. Email. March 16, 2023.

INTERPHEX Returns to NYC

The market for sustainable pharmaceutical packaging is projected to grow at a compound annual growth rate (CAGR) of 15.4% to $146.3 billion by 2027 (1). Primary packaging is forecast to register the strongest CAGR. Sustainable primary packaging materials such as eco-friendly bioplastics and biodegradable materials like paper or cellulose minimize environmental impact, reduce waste, and conserve resources. At the same time, innovative packaging designs reduce waste and carbon footprint through lightweighting and downgauging. Pharmaceutical companies also are exploring the feasibility of reducing waste by adopting reusable or refillable packaging (1).

Forces driving interest in sustainable pharmaceutical packaging include laws and regulations and a shift in consumer preferences toward recyclable and eco-friendly packaging materials (1). “Stakeholders throughout the value chain—employees, healthcare professionals, patients, policymakers, and investors—expect every business to be working toward and reporting on how they are impacting sustainability,” says Søren Tulstrup, president and CEO, Hansa Biopharma.

Lon Johnson, vice-president of Sales and Marketing at Colbert Packaging, has noticed this attitude too, especially among large pharmaceutical companies. He says, “There is a significant trend toward decarbonization and net zero goal setting, and they are encouraging supply chain participation in the effort. These North American companies are taking their cues from European counterparts who have led the charge to sustainability. We have seen an increase in supplier sustainability surveys from our customers in recent years. More and more, they are looking to work with suppliers who are committed to the same goals and vision for sustainability that they have.”

Committed suppliers are a requirement for Hansa Biopharma. Tolstrup reports, “All supplier agreements ensure that every effort is made to integrate sustainable practices into all aspects of these businesses. We work closely with our suppliers to ensure they are looking for ways to reduce waste and maximize recycling opportunities for manufacturing residuals. For instance, our supplier agreements require that partners have systems and procedures in place to safely handle waste and discharge, and to optimize the use of all relevant resources sustainably, including but not limited to, energy, water, and materials.”

Many pharmaceutical manufacturers are working toward improving the sustainability of their packaging and their operations in general. Since October 2021, when Astellas Pharma introduced a biomass-based plastic blister package in Japan for Irribow Tablet 5 µg (ramosetron hydrochloride) to treat diarrhea-predominant irritable bowel syndrome, it has expanded the use of plant-derived materials for its blister packaging. The blister package is made of polyethylene (PE) derived from sugarcane, as 50% of its raw material. A spokesperson for Astellas Pharma, reports, “This is the world’s first use of biomass plastic for blister packages for drugs. It is an environmentally friendly packaging that agrees with the concept of ‘carbon neutrality,’ which is the idea of balancing greenhouse gas emissions and absorption.” Emphasizing renewability rather than recyclability provides a blister package that can contribute to a reduction in greenhouse gas emissions.

To expand its efforts, Astellas Pharma began a collaboration in December 2022 with Eisai, Daiichi Sankyo, and Takeda to reduce the environmental burden posed by pharmaceutical packaging. Based on the agreement, Astellas Pharma will promote the use of more environmentally friendly packaging for pharmaceutical products by sharing knowledge about technologies such as biomass-based blister packs, compact packaging, recycled-content packaging materials, and recyclable packaging materials. “In doing so,” the spokesperson notes, “Astellas, Eisai, Daiichi Sankyo, and Takeda aim to ensure that society benefits from this collaboration to harmonize corporate activities with the global environment.” Moreover, the partners hope to eventually expand their collaboration to other manufacturers.

Packaging suppliers also are working to provide more sustainable options. Johnson explains, “The sustainability story is no longer a footnote or ‘nice to have.’ It has been moved to front and center in terms of corporate social responsibility. As a paperboard packaging manufacturer, we are committed to developing new and better ways to utilize paper in packaging as a 100% alternative to plastic, or as a means to using less plastic in a more environmentally friendly way.”

So, Colbert Packaging is focused on developing paperboard packaging that uses less material and offers increased recyclability. Tactics include the adoption of water- and agri-based inks, coatings, and adhesives as well as the design and engineering of lightweight, right-sized cartons. The company also practices responsible sourcing with 100% of its paperboard derived from certified, responsibly managed forests. Forest Stewardship Council and Sustainable Forestry Initiative certifications mean the firm can provide chain of custody documentation to buyers of its paperboard cartons.

“Downstream, we know that our secondary packaging materials are 100% recyclable, and most are compostable,” says Johnson. “We use various grades and types of paperboards … including 100% recycled board and other paperboards that contain post-consumer recycled content,” he adds.

More sustainable options for blister packaging include the EcoLam mono-PE family of recyclable laminates from Constantia Flexibles. Based on oriented PE in duplex or triplex structures, metallization and aluminum oxide can impart barrier properties that yield a material that can compete with aluminum foil laminates. These barrier materials are present at such low levels that recyclability of the PE is unaffected, according to RecyClass, a Europe-based nonprofit, cross-industry initiative facilitating the transition toward a circular plastic future (2).

Hansa Biopharma works to ensure its packaging is recycled and that partners understand and follow local requirements regarding packaging waste and recycling. “For instance,” says Tulstrup, “in Austria we contract with Alstoff Recycling Austria to ensure compliance with the Austrian Waste Management Act. At Hansa, we strive to make sustainable decisions across the entire value chain. Our lead molecule, imlifidase, is a cold-chain product—meaning it is temperature-sensitive and must always remain at a specific temperature. Therefore, we work with suppliers to ensure appropriate packaging and shipping are used while maintaining the temperature and protecting the integrity of the product. We also continue to investigate how to reduce the packaging required to provide the correct environment for the product given the cold-chain requirements.”

Stumbling blocks to adopting more sustainable packaging include technical issues, cost, and environmental awareness. From a technology perspective, multi-material structures make recycling difficult. Even if alternatives to foil and multi-material laminations exist, the infrastructure to cost-effectively recycle the materials must be developed and be widely available to make recycling a feasible disposal option for this type of packaging.

Cost is always part of any sourcing discussion. “There is a perception that … a more sustainable solution means added cost. Sometimes it is more costly, but it is not a given,” says Johnson. Indeed, some premium for sustainable packaging may be warranted. “Eco-friendly packaging is not always cheap, but we believe that it is a responsible investment considering the importance of the global environment,” reports the spokesperson for Astellas Pharma.

In many regions, there still isn’t enough recognition of environmental issues. “For instance,” says the spokesperson, “not everyone is aware of the carbon footprint of the packaging process or takes concrete actions to address environmental matters.”

Packaging is not the only area where pharmaceutical manufacturers and their packaging suppliers are taking steps to be more sustainable. Astellas Pharma, for example, also focuses on reducing greenhouse gas emissions.

In 2021, Hansa Biopharma assessed its business to understand priority areas for sustainable business operations and formalized its commitment to Healthy Patients, Healthy Business, and Healthy Planet. “To advance our commitment to Healthy Patients, we work closely with patient advocacy groups and healthcare decision-makers to ensure equitable access to our medicine,” says Tulstrup.

Operating a Healthy Business means focusing on the well-being of employees including safeguarding laboratory staff, eliminating gender pay gaps, and maintaining a low turnover rate.


Tulstrup explains, “We also have a robust governance structure and Employee Code of Conduct to instill a high level of integrity and value-driven behaviors throughout the organization. Additionally, we require that all vendors, partners, and suppliers sign a Supplier Code of Conduct that focuses on fair labor, ethical business practices, and health, safety, and environment practices. Underscoring our commitment to Healthy Planet, nearly two-thirds of the energy used in our operations in 2021 was completely renewable.”

At Colbert Packaging’s facility in Kenosha, Wis., it is pursuing zero manufacturing waste-to-landfill status. Johnson says, “We are proud to say that no paperboard waste from our operations goes to a landfill. Working with companies like River Valley Paper, we are recycling approximately 3000 tons of paper and production-related material in a typical year.”

Colbert Packaging also participates in alternative energy programs such as wind energy, through renewable energy credits. “By supporting Green-e Energy certified wind power, we are taking action against climate change, improving our overall environmental footprint, and having a direct impact on renewable energy projects,” concludes Johnson.

MarketsandMarkets. Sustainable Pharmaceutical Packaging Market Worth $146.3 Billion by 2027—Exclusive Report by MarketsandMarkets. News Release. Feb. 17, 2023.

Constantia Flexibles. What Is the Future of Flexible Film Packaging in a Circular Economy? Webinar. Feb. 21, 2023.


Vol. 46, No. 4
April 2023
Pages: 36–38, 49

When referring to this article, please cite it as Focinio, H. Packaging Becomes More Sustainable. 

Manufacturers and suppliers join forces to reduce the pharmaceutical industry’s carbon footprint. 

Packaging Becomes More Sustainable 

All product labeling that carries the National Drug Code (NDC) will need to be updated if FDA finalizes its proposed rule to expand the number from 10 to 12 digits. In some cases, labels also may need to allow more space for the code. The goals for the proposed rule, Revising the National Drug Code Format and Drug Label Barcode Requirements (/docket/FDA-2021-N-1351), are to standardize the format of the NDC, expand the pool of available codes, and increase the number of acceptable barcodes. Lengthening the code is necessary because the supply of five-digit labeler codes will be exhausted in 10 to 15 years. Comments on the proposed rule were due by Nov. 22, 2022 (1).

The proposed rule specifies a 12-digit NDC with three segments, a six-digit labeler code, a four-digit product code, and a two-digit package code. The effective date would be five years after publication of the final rule followed by a three-year transition period to convert existing 10-digit NDCs to 12 digits. During this period, all stakeholders would need to run systems that are capable of handling both 10- and 12-digit NDCs (1). The code change also would require updated software and employee training. FDA estimates the change will cost the industry between $43.1 and $136.3 million (2).

Many commenters agreed with the need to lengthen the NDC but raised concerns about the timeline; the number of stakeholders that rely on the NDC; the scope of the packaging, software, and system changes required; cost projections; the potential for confusion and misdosing as the longer codes are adopted; impact on the Global Trade Item Number (GTIN) code used for serialization; and the advisability of going beyond 12 digits to delay the next depletion of numbers (1). “Expanding the proposed new NDC code length to 13 digits, in a single uniform, 7-4-2 format, for example, may provide a more enduring solution,” noted Ryan Kaat, general counsel of Pharmaceutical Research and Manufacturers of America (PhRMA), in its comments (3).

If finalized, the change will reverberate across the value chain. Due to the number of parties, systems, and processes affected, GS1 US likened the impact of the change to an industry-specific Y2K (Year 2000), which necessitated updating systems to ensure a successful transition from 1999 to 2000. GS1 US noted, “There are three categories of systems impacted by the change in the NDC format: the barcoding system; the systems used by organizations within the healthcare industry; and the interfaces between organizations. The industry will no longer be able to use the linear UPC barcode due to the increased length of the NDC to 12 digits as it exceeds the maximum character allowance … This will result in a greater need to use the 2D DataMatrix barcode to carry the five product data elements (with capacity for others if necessary) within a certain space (4).”

Josh Goolcharan, director of sales and marketing for Reed-Lane, a privately held company specializing in pharmaceutical contract packaging, explains, “The logistics for implementing the changes will need to be managed to ensure there are no disruptions to the supply chain. Contract packagers like Reed-Lane will need to work closely with … their customers to see that required artwork revisions are implemented accurately and efficiently, ensuring that customer inventory levels are maintained.”

He adds, “Any of our in-house print systems currently printing either human-readable or barcode-based NDC numbers will need to be reviewed to determine compatibility with the revised format. These assessments include whether a software revision is required and whether a print system will need to be replaced to meet the new requirement.”

The potential for supply chain disruption is not limited to the availability of pharmaceutical products. Goolcharan notes, “As all packaging operations will be meeting the same implementation deadlines, the vendors that support the production of printed packaging components and serialized packaging lines may face a surge of orders, resulting in long lead times to meet the demand for the changes associated with the revised NDC format.”

Currently, each serialized package level is assigned a GTIN-14 number, and the NDC number is part of this GTIN number. The GTIN is printed in a human-readable format and included in the symbology printed on serialized packages. This scenario does not accommodate a 12-digit NDC. According to GS1 US, “The new NDC format amplifies the need to associate an NDC with a GTIN to uniquely identify a product at every packaging hierarchy. While the NDC can no longer be embedded in the product GTIN, the association of a GTIN to an NDC remains critical. The association of the GTIN to an NDC is achieved by defining NDC as AI (Application Identifier) (715) (4).”

Goolcharan observes, “Additional real estate on some packaging components may be required to accommodate expansions of printed information stemming from the revised NDC format.” In addition, he says, “…any required revisions to the software on serialized lines, or when transferring serialized data, would need to be developed, installed, and qualified so the serialized process can cooperate with the revised NDC format.”

1. FDA. Revising the National Drug Code Format and Drug Label Barcode Requirements. Proposed Rule,

Revising the National Drug Code Format and Drug Label Barcode Requirements. 

Preliminary Regulatory Impact Analysis,July 27, 2022.

Re: Docket No. FDA-2021-N-1351; Revising the National Drug Code Format and Drug Label Barcode Requirements,

 comment from ThePharmaceutical Research and Manufacturers of America. Nov. 23, 2022.

 GS1 US Comment to the United States Department Food & Drug Administration Regarding: Revising the National Drug Code Format and Drug Label Barcode Requirements Docket No. U.S. FDA-2021-N-1351, 

The change would impact every package and hundreds of systems. 

FDA Proposes Longer National Drug Code 

Blister packaging can present a quandary for solid dosage forms and products like pre-filled syringes or auto-injectors. The material(s) not only must maximize product shelf life, but also meet demand for more sustainable structures. Unfortunately, the barrier properties needed to protect shelf life often depend on multilayer materials, which often are challenging to recycle.

New materials are being designed to provide more sustainable choices. A good example is the winner in the Sustainable category in the 2022 AmeriStar Packaging Awards competition, sponsored by the Institute of Packaging Professionals. The AmSky thermoform blister system from Amcor Flexibles Healthcare North America relies on existing material, high-density polyethylene, in a proprietary formulation for the forming web and lidstock to provide a single-stream recycling option (1).

Other sustainable blister materials also are available. TekniPlex Healthcare recently introduced a fully transparent, mid-barrier polyolefin/polypropylene (PP) blister package. It’s certified to be recyclablein geographies where the #5 (PP) recycling stream is available. For products with minimum barrier requirements, TekniPlex has developed a fully recyclable polyester mono-material blister/lidding combination. “The ability to make transparent barrier blister packages recyclable is a crucial step toward healthcare materials circularity, one in which technical challenges needed to be overcome with extensive research, trials, and dedication,” said Chris Qualters, CEO of TekniPlex Healthcare (2).

TekniPlex Healthcare also has expanded its capacity for other barrier materials with the installation of a new air knife coater, which will boost the production ofcoated Tyvek, heat-seal-coated reinforced paper, and cold-seal-coated paper and film to meet performance and sterilization requirements for medical device, pharmaceutical, and diagnostic applications. Qualters said, “The state-of-the-art air knife machine will ensure we can meet escalating product demands in the North American market while also allowing us to further expand in other geographies like China, Southeast Asia, Latin America, and Europe (3).”

Expanded availability also is the driving force behind the establishment of a European manufacturing site for Activ-Blister packaging from Aptar CSP Technologies. A European contract manufacturing organization (CMO) will support regional customers and ensure speed-to-market with the installation of a fully automated Uhlmann blister machine validated to package oral solid dose drug products with Activ-Blister material heat-staked to the foil at a rate of up to 250 blisters/min. The active packaging component can be customized to provide a range of protection including moisture adsorption and oxygen and odor scavenging. The technology also can scavenge volatile organic compounds and emit aromas. The Uhlmann equipment has been fully validated at Ivers-Lee, a US CMO. “With manufacturing capabilities now available in the US and EMEA, we will turn our attention to bringing production of this technology to the Asia market,” said Badre Hammond, vice-president Commercial Operations and GM APAC, Aptar CSP Technologies (4).

Performance is the goal behind Pentapharm kpSilver blister material from Klöckner Pentaplast. The thermoformable alternative to cold-form foil looks like foil but runs as much as 85% faster and requires less material. Compatible with standard thermoforming equipment and tooling, the material seals well to vinyl-compatible lidstock. Options include a polyvinyl chloride (PVC)/polyolefin laminate or a higher barrier Aclar/polyolefin/PVC laminate. Custom structures also are available. Water vapor transmission rates as low as 0.05 g/sqm can be achieved, and its barrier to ultraviolet and visible light meets USP regulations (5,6).

1. Institute of Packaging Professionals. 2022 AmeriStar. 

2022 AmeriStar Award Winners | Institute of Packaging Professionals (iopp.org)

2. TekniPlex Healthcare. At PACK EXPO, TekniPlex Healthcare to Debut World’s First Fully Transparent Recyclable Mid-barrier Blister Package. News Release. Oct. 11, 2022.

3. TekniPlex Healthcare. TekniPlex Healthcare Invests in State-of-the-art Production Equipment for Coated Barrier Products, Significantly Expanding Capacity and Capabilities. News Release. Nov. 29, 2022.

4. Aptar CSP Technologies. Aptar CSP Technologies’ Activ-Blister Solutions Now Available for Manufacturing in the EMEA Region. News Release. May 12, 2022.

5. Klöckner Pentaplast. Specialty Rigid Films. 

Speciality Rigid Films - Klöckner Pentaplast (kpfilms.com)

kpSilver high-performace blister films (kpfilms.com)

Materials enhance sustainability and efficiency. 

New Blister Packaging Options

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

Pharmaceutical Manufacturing Trends Shaping the Future

, a report published in March 2022 by PMMI Business Intelligence, a division of PMMI, The Association for Packaging and Processing Technologies (1).

As the production of higher-value injectables and customized products grows, packaging formats and production preferences are evolving and pushing manufacturers toward more automated production lines, digitization of data, and expanded use of contract manufacturing and packaging organizations (1).

The report also notes manufacturers must adjust to steady growth in direct-to-consumer e-commerce channels and consumer preferences for sustainable practices (2). 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).

As the demand for injectables grows, so does the need for ready-to-use (RTU) vials, cartridges, and syringes. As a result, suppliers are increasing capacity. For example, SCHOTT Pharma, a standalone company established in August 2022 by SCHOTT for its pharmaceutical business, started up a production facility in Germany for pre-fillable polymer syringes; is expanding cartridge production in Switzerland, China, and Hungary; broke ground on a pre-filled syringe operation in Hungary; and plans to triple its capacity for high-quality sterile vials in the United States (4,5,6).

The additional cartridge capacity addresses the demand for drugs that are self-administered via auto-injectors, which make it easy for a patient to self-dose safely and accurately (4). The pre-fillable syringe (PFS) operation under construction in Lukácsháza, Hungary, will add a second production hub to SCHOTT Pharma’s global manufacturing network. Scheduled for completion in 2024, it will feature fully automated manufacturing processes and cutting-edge machinery, as well as an advanced camera-controlled inspection system. “With this move, we are staying one step ahead in providing high-value solutions to store biologics, vaccines, and the latest generation of mRNA-based medications,” said Andreas Reisse, CEO of SCHOTT Pharma (6).

A high-quality PFS not only offers stable, long-term storage for drugs, but also a safe and convenient delivery system for patients and clinicians. “With our PFS system, we are eliminating almost all drug injection preparation steps and thereby reducing the risk of medical errors and contaminations. This plays a vital role in the safety of health care professionals and patients,” said Christian Helbig, vice-president for Prefillable Glass Syringes at SCHOTT Pharma (6).

Two other glass container producers, Stevanato Group and Gerresheimer, have joined forces to develop RTU glass containers that will run on standard fill/finish lines and accelerate the transition from bulk to RTU containers. The EZ-fill Smart product line, a next-generation addition to Stevanato’s EZ-fill family, will share the same secondary packaging, production process, and sterilization method to ensure consistent reliable double sourcing. “Through our collaboration . . . we expect to achieve another important milestone in creating a reliable ecosystem to support, accelerate, and de-risk the conversion from bulk to EZ-fill [RTU] vials,” said Mauro Stocchi, chief business officer at Stevanato Group. “The newly developed RTU vial platform stands out in terms of quality, total cost of ownership, and sustainability, and takes the use of RTU solutions like vials, and, in the future, cartridges to a new level,” added Dr. Lukas Burkhardt, member of the Gerresheimer Management Board (7,8).

Process and product improvements and increased automation throughout the manufacturing process boost productivity and reduce human errors. The optimized process eliminates glass-to-glass and glass-to-metal contact, which improves vial quality and integrity throughout the product life cycle. Redesigned secondary packaging further enhances quality by reducing particle risks during fill/finish operations. The new EZ-fill Smart line also eliminates traditional ethylene oxide (EtO) sterilization and is validating a safer, more environmentally friendly sterilization method, which meets guidelines given by regulatory bodies supporting the transition away from EtO sterilization (8).

Developed in close cooperation with major machine vendors, the EZ-fill Smart line seamlessly integrates with standard fill/finish operations and accommodates small- and large-batch production. Designed to automate the infeed process, EZ-fill Smart containers will be available in nest-and-tub and tray configurations. EZ-fill Smart containers in nest-and-tub arrays are scheduled to be available in mid-2023 for initial validation and by mid-2024 for commercial use. A tray configuration for high-volume applications is expected to be available during the first half of 2024. “The new platform will enable customers to optimize their processes, improve their quality and their carbon footprint. In addition, our customers can benefit from a significant reduction in the total cost of ownership,” said Burkhardt (8).

Stevanato is also partnering with DWK Life Sciences to distribute its RTU EZ-fill vials in nest-and-tub and tray configurations and EZ-fill cartridges in nest-and-tub arrays. The pre-sterilized containers streamline the fill/finish process, reduce total cost of ownership, and shorten overall time-to-market (9).

A potential alternative to glass containers, MSI-TX thin film, under development by Jurata Thin Film, stabilizes biologic materials (live virus and bacterial-based vaccines, as well as antibody-based therapeutics) in a film matrix for ease of shipment, storage, and administration (10). “All components of our thin film, except for one, are considered generally recognized as safe (GRAS) by the US FDA,” reports Megan Livingston, senior director of Business Development at Jurata Thin Film. She notes, “The one component that is not GRAS is undergoing toxicity studies now, the results of which will be submitted to the FDA in a Type IV Drug Master File. With that said, the amount of the novel excipient included in our formulations is so low that we do not anticipate any negative toxicity results.”

The thermostable nature of the film maintains the therapeutic efficacy of its payload, eliminating the need for lyophilization and cold-chain logistics and enabling a transition from temperature-controlled cargo containers to a sterile envelope, which can travel through normal mail channels (10). Livingston says, “For our pilot line, we are utilizing in-blister manufacturing, so our thin films will be dried within their primary packaging. This primary packaging will be labeled and put into secondary packaging for shipment/distribution.”

The thin film is adaptable to a variety of biologics, processes in about three hours, and is easily transferable to industrialized and developing countries. It has been validated with several active pharmaceutical ingredients, including influenza and Ebola vaccines, as well as live bacteria at room temperature
(20 °C) for extended periods (six months to three years). Juarta can provide the technology to pharmaceutical companies for in-house use or serve as a contract manufacturer using bulk API as a starting material (10). “We typically require about four weeks to optimize the formulation of a new vaccine or biologic,” explains Livingston.

MSI-TX thin film can deliver vaccines and therapeutic payloads through buccal or sublingual routes or be rehydrated to recover the therapeutic payload in an aqueous solution to be administered intranasally or parenterally. These routes of administration can improve the potency of biologics without using needles, for non-invasive vaccine and drug delivery. Juarta Thin Film also is optimizing the MSI-TX thin film for rapid and/or continuous release of therapeutic payloads, further increasing potential applications (10).

Pharmaceutical production lines are becoming increasingly automated to boost production, offset labor shortages, and minimize human interaction with parenteral products. Automation also is key to the flexibility and quick changeover today’s lines need to efficiently run multiple products, packaging formats, and sizes, as well as address the requirements of the direct-to-consumer channel. As a result, the use of robotics, increasingly supported by vision technologies and artificial intelligence, is growing (11). In fact, according to the PMMI report, 

, nearly three-quarters of respondents use robotics now and 53% plan to expand deployments for secondary and tertiary packaging applications (12).

Even quality control systems are becoming more automated. For example, PTI has introduced the modular E-Scan RTX model, a fully-automated container/closure integrity tester for pre-filled syringes. Its adaptable robotic design relies on micro-current high-voltage leak detection, which is compatible with delicate biologic liquids, including those with extremely low conductivity. The test yields a pass/fail result in seconds. Listed in 

Chapter <1207> as a recommended method for parenteral liquid package inspection, the system offers a good signal/noise ratio between good and defective products. Low-voltage exposure reduces the production of ozone (13).

Meanwhile, the pace of digitization is accelerating to meet regulatory requirements, address cybersecurity concerns, achieve operational visibility, and support blockchain product tracking (12).

The global pharmaceutical contract packaging market reached US$18.44 billion in 2021 and is forecast to expand at a compound annual growth rate of 8.07% through 2027, according to a market study available from Research and Markets (14). This forecast tracks with information in the PMMI report, which notes three out of five pharma manufacturers outsource at least a
portion of their operations to a third-party contractor (12).

Contract manufacturing and packaging organizations help pharma manufacturers address the growing demand for injectables and personalized medicine. Benefits of hiring a third party include access to formats and production methodologies that are not available in-house, accommodating spikes in demand, and cutting costs by eliminating the need to source, install, and validate new machines and lines. This also frees up capital for use elsewhere in the operation (12).

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

2. Forcinio, H. Consumers Seek Sustainable Products. 

3. PMMI, The Association for Packaging and Processing Technologies, Pharmaceutical Manufacturing, The Future Ahead. Infographic. Undated.

4. SCHOTT, SCHOTT Establishes Stand-Alone Company for Its Pharma Business to Promote Further Growth. Press Release. Aug. 1, 2022.

5. SCHOTT Pharma, Simplifying Self-medication: SCHOTT Pharma Expands Cartridge Production in China and Hungary.Press Release. Sept. 22, 2022.

6. SCHOTT Pharma, Driving Growth for Prefillable Glass Syringes: SCHOTT Pharma Breaks Ground for Cutting-edge Production in Hungary. Press Release. Oct. 27, 2022.

7. Stevanato Group, Stevanato Group and Gerresheimer AG Together to Develop an Innovative RTU Vial Platform. Press Release. Sept. 7, 2022.

8. Stevanato Group, Stevanato Group and Gerresheimer AG Present EZ-fill Smart, a New and Innovative Ready-to-Use Vial Platform. Press Release. Nov. 1, 2022.

9. Stevanato Group, DWK Life Sciences and Stevanato Group Sign Non-Exclusive Distribution Agreement for EZ-fill Platform Products. Press Release. Oct. 27, 2022.

10. Juarta Thin Film, Our Technology, The MSI-TX Thin Film. www. juratatf.com/our-technology, accessed Nov. 30, 2022.

11. PMMI, The Association for Packaging and Processing Technologies,

 The Future of Automation in Packaging and Processing

12. PMMI, The Association for Packaging and Processing Technologies, 

13. PTI, PTI Launches E-Scan RTX Automated CCI Solution for Pre-filled Syringes at PACK EXPO International. Press Release. Oct. 17, 2022.

14. 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. 

When referring to this article, please cite it as H. Forcinio, "Packaging Formats Evolve," 

Manufacturers automate production lines and increase the use of third-party providers. 