The pharmaceutical industry has always maintained a prevalent place in the United States economy. The sheer size of this industry places a significant emphasis on the labeling of these items. Unlike labels in other sectors, a mistake on a pharmaceutical label could pose life or death consequences. The global Covid-19 pandemic has only magnified the spotlight on this critical industry.

Citing a newly published report from Acumen Research and Consulting, titled, Healthcare and Laboratory Labels Market: Global Industry Size, Share, Trends and Forecast 2021 – 2028, Cory Keller, senior product manager – pharmaceutical, Avery Dennison Label and Packaging Materials, says the global healthcare and laboratory labels market is expected to grow at a compound annual growth rate of 5.5% between 2021-2028 up to a total value of $9.4 billion, with North America the largest region, representing 38.24% of global market share.

Specific to pharmaceutical and nutraceutical labels, the global revenue in 2020 was $2.96 billion, and it is expected to grow to $7.72 billion in 2028, with a compound annual growth rate of 6.0% from 2020 to 2028.

“The most important features of a pharmaceutical label are functionality, consistent quality and security features, as well as having enough real estate to communicate all necessary information,” says Leslie Gurland, executive vice president, global sales and marketing, Lux Global Label.

Covid-19, of course has played a large role in this labeling market. “In recent years the growth of biologic drugs, including the vaccines developed to fight the Covid-19 pandemic, has put a spotlight on the fragility of the pharmaceutical supply chain,” says Keller. “The industry’s migration to these new medicines (most large pharmaceutical companies are now spending 40-50% of their R&D budgets on biopharmaceuticals) has significant ramifications from a labeling standpoint, as many biologic drugs must be manufactured, transported and stored in controlled temperatures, in some cases as low as -103F as in the case of Pfizer’s Covid-19 vaccine.”

As Tom Spina, president of Luminer Converting Group, notes, “Quality is of the utmost importance in this sector – even more so than price. Quality leads to safety throughout all levels of the supply chain, especially when labels must perform in a variety of conditions.”

Sean Flanagan, product manager, Pharma, UPM Raflatac, Americas, concurs. “The primary emphasis is on product safety and performance in challenging conditions,” he says.

An effective pharmaceutical label should boast flexibility, the correct adhesive properties, printable topcoats, durability and more. For example, labels must be able to withstand any number of exposures, including extreme temperatures.

“Films must be conformable and flexible to wrap and contour to tight radius containers yet have some dimensional stability for high-speed dispensing,” states Lori Bitar, product manager, Healthcare, FLEXcon. “Meanwhile, adhesives must have good initial tack and a balance of high peel and shear properties. Shear is an important function to allow for high performance and adhesion to tight radius containers. Many critical labeling materials are clear films backed with clear polyester liners. A luminescence can be added to the adhesive of these clear-on-clear materials so that the labels can be sensed in a high-speed dispensing line.”

There are a number of equipment and supply requirements for pharmaceutical label printers, as well. Utilizing 100% inspection on-press and finishing equipment is imperative. Plus, companies must maintain a full lab with testing equipment, which can include testing variable printing, back numbering and more. Digital label authentication systems are also prevalent in this space.

This is a changing industry, too. The advancements of security and tamper-evident features have promoted the ability to fight counterfeiting. Suppliers have designed numerous overt, covert and forensic solutions, such as destructible and semi-destructible films, holographic films, fluorescing adhesives, and micro-taggants to advance this sector.

“Trends like supply chain integrity, digitization and sustainability will continue to play an important role in pharmaceutical labeling,” states Gene Dul, president of Schreiner MediPharm. “Labeling suppliers must provide innovative customized solutions optimally adapted to specific applications and packaging formats while also addressing market trends and evolving industry challenges. Expertise in label technologies, combined with deep market knowledge, is the basis for novel and reliable solutions that benefit both brand owners and patients.”

NanoGrafix, for example, has engineered a wide range of products to protect and authenticate the contents of pharmaceutical products. These micro-embossed optical structures deliver several levels of security, including tamper-resistant labels, and they can be customized to meet the needs of pharmaceutical label converters.

NanoGrafix has developed special applications to the substrate, such as demetalized areas, to ensure that critical information is always legible and remains visible. Other security features to protect pharmaceutical labels that can be added are UV invisible inks, tamper-evident protection, and variable data such as serial numbers, QR codes and more.

“The industry has been looking for a very long time for a unique identifier that can’t be counterfeited, and this is it,” president and CEO Dan Lieberman says of his company’s Digital Variable Holography. “We are already exploring this with banknote printers and other security printers and converters, such as those in pharmaceuticals.”

Holograms can provide overt first-line authentication while covert features, such as scrambled images, microtext, UV-sensitive or other specialist inks, provide second line authentication for trained examiners and appropriate decoding equipment. According to NanoGrafix, US Congress is currently considering making the use of security-markings on some pharmaceutical products mandatory using “optically variable counterfeit-resistant technologies” to protect consumers.

Of course, smart labeling is continuing to make strides, as well. “Smart label technology introduces new elements beyond the barcode and serialization of the product,” explains Bitar. “Increased usage of RFID and RAIN technology, as well as sensors incorporated into label systems, provide enormous benefits to the OEM. Items can be tracked and located at any time during transit or in storage without the need to manually scan. These smart labels validate authentication, manage the flow of inventory to prevent shortages, indicate shock or sudden drastic movement, indicate temperature extremes, etc. – all of which can validate the drug’s efficacy for use.”

Another trend, notes Bitar, is the increase of aseptic filling processes in clean room environments. This trend has increased the need for plastic films and plastic liners as compared to paper films and paper liners because paper is prone to processing dust debris and, therefore, is typically not an option for these applications.

Like other segments, sustainability is poised to have an impact in pharma. “Pharmaceutical companies have begun to develop ambitious corporate sustainability goals to address some of the key challenges in the industry,” explains Keller. “Novo Nordisk, for example, has established a set of 2030 goals that includes redesigning products to reduce waste and solve end-of-life challenges so materials can be recovered and recycled into new products. GlaxoSmithKline (GSK) has developed similar goals that include 100% of materials being deforestation free. This will have an impact on label materials used in the future that will need to be sustainably-sourced, including those with recycled content and better recyclability.”

Regulations and specifications

Regulations play a pivotal role in the pharmaceutical space, and with good reason. Most of the regulations apply to what is printed on the label such as those elements necessary for tracking and tracing and product identification. The Drug Supply Chain Security Act dictates that linear and/or 2D barcoding and serialization (dependent on the product) must be printed on the label.

Pharmaceutical labels typically include information about the product, such as batch number, manufacturing date and expiration date, along with other information for the consumer and medical professionals. 

According to FLEXcon’s Bitar, the market has its sights set on November 2023, when the needs for achieving interoperability within the drug supply chain, DSCSA, will need to be achieved. “The interoperability that must be in place by 2023 will be a significant focus for all points in the supply chain, including print service providers,” she says. “The ability to trace the product from origination through to patient delivery is critical.”

Regulations, like the EU Falsified Medicine Directive, which became mandatory in February 2019, are important steps for protecting medicines against counterfeiting. Medicine packages must be provided with an individual 2D code serial number and a tamper protection feature.

“Pharmaceutical manufacturers should be aware that these measures alone will not guarantee a product’s integrity and authenticity,” comments Schreiner MediPharm’s Dul. “Only additional counterfeit-proof authenticity features can provide a comprehensive approach against fraud, misuse and tampering. Tailored security labels can combine clear first-opening indication with additional multi-level authentication features.”

The FDA plays a critical role in determining the information required on the label. Plus, the FDA must provide approval of the text before labels can be produced. “Regulations make it extremely difficult to make material changes, and this is extremely challenging with the current supply chain constraints,” says Lux Global Label’s Gurland. “For example, Lux supplies labels for a life-saving drug, and the material used was unavailable for a few months. There was only one material on the spec, and due to regulations we could not substitute the material. Luckily the material became available before there was a true crisis to patients. It was difficult because we were not allowed to substitute.

“When our pharma customers are launching a new drug, time is of the essence,” adds Gurland. “Often, they will get approval and Lux will then produce the labels within 24-48 hours.”

Avery Dennison maintains a Drug Master File (DMF) with the FDA that contains detailed information and testing on its pharmaceutical grade adhesives that can be referenced by the FDA during submission to assist with the approval process. Other application-specific regulations also exist, as in the case for blood bag labels, which must meet FDA’s Guidelines for the Uniform Labeling of Blood and Blood Components.

Risk assessment principles should be followed when evaluating against applicable FDA regulations and guidelines for a label’s intended pharma end use, especially for liquid-based products.

“Ultimately, the FDA’s evaluation of an end user’s risk assessment will be performed on a case-by-case basis when the FDA evaluates the end user’s finished packaging product as a whole through the appropriate review process,” says UPM Raflatac’s Flanagan. “While product components do not typically need premarket clearance on their own, there are standard packaging regulations and guidelines that apply, depending on the component’s intended use.

“It’s also important to note that if a pharma product is prefilled – as opposed to an empty container – the product could be considered as a drug,” he adds. “In such a case, a look to a different FDA regulatory approach may be required.”

Label manufacturers should also consider the materials that make up the labels – being FDA approved for indirect food contact and or ISO 10993-5, -10 compatible for plastic container labeling, as well as other durability requirements. “All of these are important, but one should ask about adhesion requirements,” says Bitar. “What regulations encompass the issue of labels not adhering to the container? There is so much focus on what is printed on the label and little to no focus on the survivability of the label – the ultimate adhesion to the container for the life of the product.”

Forecasting the future

The future of pharmaceutical labeling will very much center on the advancements in security and tamper-evidence, as well as track-and-trace capabilities throughout the supply chain.

“Pharmaceutical OEMs spend millions of dollars and many years developing drugs,” explains FLEXcon’s Bitar. “They conduct trials to learn of the efficacy of their products before going to market. If their drug treats a rare disease and/or becomes widely used, along with high drug prices, there is a high probability that someone will attempt to counterfeit it. With a supply of counterfeit copies on the market, over time the drug will have a higher level of adverse events, and its efficacy will be decreased as the adulteration has proliferated the brand. This is a huge problem for drug OEMs.”

The continued supply chain constraints will also play a big role for pharmaceutical label converters – specifically with material allocation. “We believe this is forcing a change whereby pharma companies will consistently have two materials on a spec,” comments Lux Global Label’s Gurland. “Up until now, the pharma companies felt giving up precious line time for qualifications was too valuable. Now, they are realizing that not having labels is a much greater problem. One of Lux’s customers summed it up perfectly – ‘speed is the next currency.’ The future is focused on supply chain reliability,” she adds.

Seeing continued success in the pharmaceutical space will also be contingent on the industry’s ability to navigate a host of challenges. One of the biggest obstacles in developing new and efficient labeling materials is time.
“The pharmaceutical industry is typically slow to adopt change for even the label components,” explains Bitar. “Timing is critical, and the qualification of new materials can take time. As a result, converters and OEMs will often revert to the labelstock they know for new applications with a goal of lessening the time required for testing and qualification. However, this tactic does not allow for the qualification of new materials that may be more appropriate for the application requirements.”

Product selection

Suppliers have responded to the ever-changing needs of this market with a host of new products.

According to the World Health Organization (WHO), up to 50% of vaccines are wasted globally every year due to improper temperature management in the supply chain. Avery Dennison’s Cold Chain and Cryogenic Portfolio can help ensure clear identification of biological materials from collection to storage, transportation and delivery – even in harsh deep freeze environments like dry ice (-109F) and liquid nitrogen (-320F).

Avery Dennison also offers a core Pharmaceutical and Healthcare product line  that is suitable for many consumer (over the counter medications and nutraceuticals) and ethical (prescription drug) applications. In addition, the company has developed several application-specific portfolios, including: Syringes, Cold Chain & Cryogenic, Blood & IV Bags, Security, Medical Device and Intelligent Label.

The FLEXcon PHARMcal product portfolio includes high performance label materials for labeling small diameter ethical drugs, over-the-counter drugs, and cryogenic samples. The line also offers products for blood management track and trace, tamper-evident labeling, as well as opaque materials for clinical trials. Films are the preferred choice for pharmaceutical applications because they can better withstand harsh conditions such as water baths or other sources of moisture and condensation.

“Our PHARMcal Supreme line contains products made of polypropylene and polyester films coated with high-performance permanent solvent acrylic adhesives backed with polyester liners,” says Bitar. “The products are used for the most critical labeling components such as those for the flu and Covid vaccine.”

Schreiner MediPharm offers a broad portfolio of customized labeling solutions for the pharmaceutical market. These include labels with integrated hangers for infusion bottles, labels with detachable documentation parts, and booklet-labels for extensive product information in multiple languages. Needle-Trap, a label with an integrated needle catcher for pre-filled syringes, helps avoid needlestick injuries.

“For product and brand protection, Schreiner MediPharm also develops label solutions that can provide reliable tamper evidence and clear first-opening indication,” explains Dul. “Frequently, such solutions entail integrated multi-level security features, ideally combining analog and digital features that support end-to-end supply chain integrity. Smart labels with integrated RFID/NFC chips enable interactive applications, such as for digital patient support, product identification or inventory management.”

UPM Raflatac has designed a pharmaceutical portfolio that can service a wide range of pharmaceutical end uses, including migration-safe, tight mandrel, CRYO, and more. “We will adapt to market trends, including staying up-to-date with any regulatory requirements and sustainability goals,” concludes Flanagan.

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Phoseon LED brings sustainability and productivity to pharma packaging

Sustainability is a major trend in label and package printing, and that is especially true in the pharmaceuticals space. There is a major shift to move from toxic, inefficient mercury UV lamps to LED because of all the sustainability and performance benefits they provide. Phoseon has been working closely with customers to support the transition from mercury to UV LED.

The environmental benefits of UV LED curing in the printing process are numerous and significant, making it attractive to brand owners and end users. Phoseon customers have experienced energy savings up to 85% with the implementation of UV LED curing systems. Conversely, mercury lamps produce ozone, which is dangerous to breathe, especially in a constricted space like a print shop. Air exhaust systems are required to extract the toxic fumes from working areas. These exhaust systems can be completely eliminated with UV LED curing. Phoseon’s LED offerings provide various environmental and sustainable benefits for both brand owners and suppliers alike.

Energy savings, pollution prevention, and waste reduction are all associated benefits of this technology. For example, UV LED lamps offer better than 50% lower CO2 emissions. Studies have shown that in certain applications, replacing mercury lamps with UV LED lamps can lead to 67 tons of CO2 reduction per year. Conventional mercury lamps need to be replaced every 1,000-2,500 hours. 

These benefits are especially relevant to pharmaceutical label and packaging converters. One trend Phoseon has noticed is the increased production of pharmaceutical label printing in response to the Covid-19 pandemic, as well as the pharma industry’s drive to develop vaccines and other therapies. Pharma customers are demanding faster and more reliable printing processes with increased throughput to achieve the increased demand for labels and packaging.

Phoseon UV LED light sources are ideal for high-speed curing and increased throughput, enabling end users to print on a variety of packaging materials at higher speeds. The intense output, low heat, and reduced energy usage of UV LED systems have enabled end users to decrease material waste and operating costs while providing customers with superior product. Users of UV LED curing systems can process a variety of materials (including thin and heat-sensitive substrates) at maximum production speeds with low-input power. 

Phoseon’s extensive portfolio of UV LED curing systems come in a variety of sizes to match various print widths. Products are available in both air-cooled and water-cooled designs to support a variety of print environments.