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Innovations address supply-chain constraints, serialization, and new requirements for sustainable and patient-centric designs.
Solid-dosage forms continue to play an essential role in the pharmaceutical marketplace despite the attention the COVID-19 pandemic has focused on parenteral products. Factors spurring demand for solid-dose products include the development of new chemical entities, especially in oncology; more complex formulations and formats; and the adoption of technologies such as microencapsulation, taste masking, and mini-tabs.
The solid-dose market also benefits from “the growth and continual rise in generic pharmaceutical companies and their impact on the accessibility and affordability of healthcare,” says Guy Calcagno, vice-president Global Sales, Films & Foils, ACG, a supplier of barrier packaging substrates.
Perhaps most importantly, consumers like the solid-dose format. “Many consumers still prefer [solid-dose] products because of their convenience for ease of dosing and portability,” explains Justin Schroeder, global vice-president, Product Development and Commercialization, PCI Pharma Services, a contract development and manufacturing organization (CDMO), which offers packaging and clinical trial services.
“Oral solid-dose products are … the easiest format to increase patient regimen compliance,” adds Francois Bidet, vice-president of Business Development EMEA for Aptar CSP Technologies, a supplier of drug delivery, consumer product dispensing, and active packaging products.
Demand for solid-dose products is more intense outside North America. “We are seeing strong growth in developing markets, such as the Middle East, Southeast Asia, India, and Latin America,” reports Calcagno.
Schroeder agrees, noting, “The pharmaceutical industry has capitalized on the opportunity to provide rest-of-world nations with more medicines and therapies, bringing life-saving treatments to new patient populations.” Delivering solid-dose products to isolated markets is much simpler than handling biologics, which require cold-chain storage.
Although bottles still account for the largest share of solid-dose packaging, the blister packaging format is showing strong growth worldwide. One forecast predicts pharmaceutical blister packaging will experience a 5.1% compound annual growth rate to reach $8.9 billion by 2031 (1). Unit-of-use blister packaging dominates in developing markets due to price-point advantages that make medication more affordable and barrier structures that can protect the shelf-life of sensitive drugs, even those destined for sale in markets with extremely hot and/or humid weather.
To protect product shelf life in these areas and expedite time-to-market, pharmaceutical manufacturers, contract packagers, and material suppliers devote considerable attention to selecting packaging with optimized barrier properties. “Given the increasing pressure to accelerate the timeline through the clinical phases and to commercialization, schedules for traditional drug formulation activities are often compressed, resulting in medicines that are sensitive to environmental degradants such as oxygen or moisture,” explains Schroeder. As a result, PCI Pharma Services offers a range of packaging options so drawbacks and benefits can be assessed for each material. With that information, the best match of product requirements and package structure can be made for the destination market, thereby enabling a seamless transition from clinical to commercial production. “This means … making our best recommendation to meet ... timeline, budget, and current global supply-chain conditions,” says Schroeder.
In addition to emphasis on barrier structures, Calcagno says, “There is a move away from polyvinyl chloride (PVC) to more sustainable packaging solutions.” Serialization is also top-of-mind with a desire to meet US Drug Supply Chain Security Act (DSCSA) requirements (including aggregation) ahead of the Nov. 27, 2023 deadline for data exchange and product verification.
Other solid-dose trends include a strong interest in patient-centric packaging. Patient-centric packaging provides intuitive design and support that helps consumers take the medication as prescribed, maximizes adherence, and ensures positive outcomes. It can also be a market differentiator for the product. A patient-centric package developed by PCI Pharma Services for a daily-dose preventative therapy, for example, combines intuitive instructions and labeling, ease-of-use, and portability while balancing child-resistant features and consumer-friendly access.
From a business perspective, solid-dose manufacturers are outsourcing more production to CDMOs. Industry stakeholders also are coping with dramatic increases in the costs of raw materials and overcoming supply-chain constraints.
Rising costs, tight supplies, and long lead times are not uncommon today for both product ingredients and packaging materials. “The COVID-19 pandemic has wreaked havoc in the manufacturing of solid-dose bulk [drugs],” reports Pat Elvin, president of Reed-Lane, a privately held company specializing in pharmaceutical contract packaging. He explains, “This shortage of supply is due to an inability to obtain all ingredients and the lack of employees to operate these facilities at this time.” Paperboard and paper stock for labeling have been in particularly short supply. “Therefore,” he says, “when we look at the private-label market, we are seeing that companies are holding their supply-chain inventory extremely tight, and packaging operators are seeing more line changeovers to accommodate smaller and shorter packaging runs.” An agile supply-chain approach and production schedule are needed.
PCI Pharma Services is focusing on supply-chain tools to improve its ability to respond to changes in the market. Its goal is to enhance productivity and provide instant feedback to all stakeholders by better resource management and material allocation. The CDMO’s pci | bridge digital platform shares real-time insights, customizable reports, and digitized workflows to ensure all factors are included in a connected digital supply chain. Schroeder notes, “We also leverage digital tools within our manufacturing environment to make client supply chains more agile and create supply-chain efficiencies, optimized inventories, and predictive analytics.”
To meet sustainability, serialization, and supply-chain issues, CDMOs are expanding packaging material options; adding or upgrading equipment, lines, and technologies; and optimizing operations and supply chains. Adare Pharma Solutions, for example, has added capacity and is completing validation of a high-speed blister packaging line with integrated cartoning and palletizing. Expected to be operational this year, the line will handle traditional solid-dose formats as well as orally dissolving tablets. Other improvements at Adare Pharma Solutions include an expanded vault for products restricted by the US Drug Enforcement Administration and the startup of high-speed stick-pack equipment for filling powders and granules. The company also is on schedule to implement full-scale aggregation capability before the end of 2022, well ahead of the November 2023 DSCSA deadline.
On the materials side, innovations include new materials, barrier substrates, and more sustainable substrates. ACG Films and Foils, for example, has developed high-barrier polyvinylidene chloride (PVDC) films, more sustainable alternatives to PVC, and a five-layer cold-form foil.
Another alternative to PVC is the AmSky thermoform blister system from Amcor. Based on polyethylene (PE), the printable material contains no vinyl or aluminum foil and is compatible with PE recycling streams. Barrier properties are said to be equivalent to a 120-gram coating of PVDC. Processability is equivalent to existing materials, and structures can be child-resistant (2).
SÜDPACK Medica also has developed a more sustainable blister film that is a coextruded polypropylene (PP) designed to replace PVC/PVDC blister materials. “PP as a raw substance basis naturally provides an outstanding steam barrier,” noted Michael Hermann, head of Research & Development at SÜDPACK Medica, in a press release statement. The coextrusion technology offers the potential for enhanced barrier properties and closed-loop material management (3).
To prevent API degradation, enhance product stability, and extend shelf-life, Aptar CSP continues to develop its Activ-Blister technology. The Activ-Blister structure adds an engineering polymer film to lidstock to control moisture and oxygen levels in the headspace of each blister cavity. “Activ-Blister also helps avoid complex and lengthy reformulations for oral-solid-dose products to withstand harsh climate conditions, such as International Conference on Harmonisation (ICH)3 (hot and dry) and ICH4 (hot and humid) zones,” reports Bidet.
With counterfeiting an ever-present concern, Holographyx is working with Hazen Paper and Uhlmann Packaging to develop, test, and launch its Holo-Blister technology. Recently granted patents in both the US and Europe, the Holo-Blister technology enables conventional heat-seal blister packaging equipment to cost-effectively apply custom holograms to the back of blister packs. Holo-Blister holograms are designed to only be visible behind each pill/capsule cavity on the back of each blister pack, providing instant verification of authenticity, while leaving space around the recess to print dosage and marketing information (4).
Future developments will center on serialization, active packaging, and sustainability, as well as the flexibility to efficiently accommodate shorter runs and frequent changeovers. For example, more efficient serialization equipment is needed, says Renard Jackson, vice-president of North American Contract Service Operations at Adare Pharma Solutions.
Active packaging will make it possible to tailor containers and substrates to the specific sensitivities of various APIs. As a result, Bidet says, “New chemical entities will be more stable and can be launched on a worldwide scale more efficiently and effectively.” Time to market will accelerate.
Sustainability is top-of-mind for everyone. “There’s currently a significant push in the pharmaceutical industry to consider sustainability and eco-friendliness when designing packages,” reports Schroeder. “Pharma companies will need to consider lifecycle assessments of various oral solid-dose products; [this] holistic perspective includes manufacturing, packaging, and transport,” adds Bidet.
“Many traditional high-barrier films are not easily separated for traditional recycling streams,” notes Schroeder. So, film manufacturers are working on materials that are easier to recycle. Thus, Calcagno says, “I believe we will see a huge influx of more cost-effective alternatives to PVC-based films.” Bidet predicts, “Monomaterial or compatible recycling stream material will be preferred.”
“With the introduction of these new materials, equipment will continue to evolve to properly accommodate them,” says Schroeder. He concludes, “By 2025, we’re going to continue to see the evolution of packages, with a continued focus on creating more patient-centric delivery to ensure successful health outcomes while also introducing a more sustainable approach for cradle-to-grave packaging lifecycles.”
Hallie Forcinio is packaging editor for Pharmaceutical Technology
Vol. 46, No. 4
When referring to this article, please cite it as H. Forcinio, “Meeting Challenges in Solid-Dose Packaging,” Pharmaceutical Technology, 46 (4) 2022.