Felicity Thomas is Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Felicity Thomas

Flexibility and adaptation concept. Arrows on cubes following a flexible path | Image Credit: © Cagkan - stock.adobe.com

Flexibility in pharmaceutical manufacturing is becoming an increasingly pertinent requirement. Various industry trends, such as the development of increasingly complex and novel therapies, a greater focus on orphan drug designation, and the use of more highly potent ingredients, are leading to demand for adaptable and versatile processing equipment.

“For decades, large-scale drug production was the industry standard. However, the rise of rare diseases now demands increasingly expensive medications, which, in turn, require greater research and development efforts, including innovations in machine design,” remarks Andreas Mattern, vice-president Strategy and Global Product Management Pharma at Syntegon. “For example, there is now a need for machines capable of processing small and micro batches with greater flexibility. At the same time, new drugs like anti-obesity medication are sustaining the demand for high-performance equipment that can handle large batch volumes.”

“There have been significant advances in flexible manufacturing to accommodate the rapidly changing therapeutic landscape, particularly in response to the rise of personalized medicine, biologics, gene and cell therapies, and the need for rapid responses to health crises (like the COVID-19 pandemic),” specifies Caterina Funaro, Competence Center manager at IMA Active. “These advances are helping the pharmaceutical and biotech industries adapt to smaller batch sizes, varied production processes, and the need for faster, more adaptable production cycles. Key innovations in processing equipment, facility design, and digital technologies are enabling greater flexibility in manufacturing.”

Specialized treatments are certainly driving new equipment developments, confirms Mattern, who points out that personalized therapies are becoming a focus for future treatment breakthroughs. “Many types of cancer and genetic disorders can only be treated with highly specialized drugs,” he says. “These [drugs], in turn, require production in ever smaller batch sizes.”

New therapeutic modalities, such as cell and gene therapies, require flexible equipment that can handle fast changeovers from one product batch to the next, Mattern continues. “A wide variety of products must be filled into different container sizes and types such as vials, syringes, or cartridges. Hence, it comes as no surprise that the market for ready-to-use (RTU) containers has been growing at a rapid pace over the past years,” he says.

Benefits of RTU containers include reduced time-to-market, lower cost of ownership, increased flexibility, and greater integrity of the drug product, explains Mattern. “While RTU containers have been the de-facto standard for pre-filled syringes for some time, they are now also increasingly being used for vials and cartridges in both bulk and small batch applications,” he states.

A general move away from traditional approaches to manufacturing has been trending for a while, comments Funaro. “Continuous manufacturing (CM) has gained traction as an alternative to traditional batch production,” she adds. “[CM] provides greater flexibility by allowing production to run continuously, without the need for lengthy shutdowns between batches, which is especially beneficial for both small- and large-scale manufacturing.”

“The industry has made significant progress in adopting continuous processes, which are progressively replacing traditional batch processes, particularly in the pharmaceutical, chemical, and food processing sectors,” explains Funaro. “Continuous processes offer enhanced efficiency, higher throughput, better product consistency, and improved energy use, driving their adoption across industries.”

For pharmaceuticals, manufacturers are employing continuous processes to API production, granulation, mixing, tableting, and coating, remarks Funaro. Through using continuous processes for these tasks, companies are being able to reduce lead times, improve product consistency, and facilitate any potential scale changes that may be required to meet therapeutic demand, such as increased production of vaccines or biologics, she confirms.

Within the oral solid dosage (OSD) space, CM has been trending for a few years, Mattern adds. “Higher flexibility, shorter development times with minimum API usage, and a direct transfer from development to production without scale-up are among the primary requirements of pharmaceutical manufacturers,” he says. “The main challenge with traditional solutions is the precise dosing of the starting materials in a constant mass flow rate of milligrams per second.” However, as the pharmaceutical industry is highly regulated, adopting newer processes can take time, Mattern specifies.

“FDA has endorsed continuous processes, recognizing their potential for faster production and more consistent product quality,” asserts Funaro. “As a result, manufacturers are investing in equipment such as continuous coaters and continuous mixers.”

Additionally, while investment in continuous processes grows, advances are also being seen in real-time data monitoring tools, which are vital in helping to control variables in CM, such as temperature, pressure, and product quality, continues Funaro. “Real-time analytics are increasingly being integrated with machine learning (ML) algorithms to allow for self-regulating systems that automatically adjust process parameters to maintain optimal efficiency and output quality,” she says.

“The shift from batch to continuous processes is well underway, but ongoing advances in processing equipment will further accelerate the transition,” asserts Funaro. “As technologies such as real-time monitoring, modular designs, AI [artificial intelligence] integration, and energy-efficient systems mature, industries will be able to harness the full potential of continuous processes, resulting in lower costs, higher productivity, and improved sustainability.”

“Automation is playing an increasingly critical role in processing equipment across industries such as pharmaceuticals, food and beverage, chemicals, and biotechnology,” explains Funaro. “The current trends in automation are transforming manufacturing processes by enhancing productivity, improving consistency, ensuring quality, and reducing human error.”

Through the use of automation, manufacturers can achieve a multitude of benefits. For example, Funaro points out that automated material handling, packaging, and processing reduces human intervention and speeds up cycle times. Additionally, she alludes to the fact that automation reduces variability in production processes, which ensures consistent quality.

For Funaro, the use of digital twins, which are virtual replicas of physical processes or equipment, will become more widespread within industry over time. “Digital twins allow manufacturers to simulate process changes, predict how equipment will behave under different conditions, and optimize production before making physical adjustments,” she says.

“Predictive maintenance is becoming a standard practice, leveraging AI, IoT [Internet of Things], and analytics to predict when equipment will fail, and schedule maintenance before a breakdown occurs. This reduces unplanned downtime and extends the lifespan of processing equipment,” adds Funaro. “As predictive maintenance becomes more advanced, it will shift toward prescriptive maintenance, where AI not only predicts failures but also suggests the optimal maintenance actions to take, further minimizing disruption and cost.”

While digitalization is producing large amounts of data in production every day, it will mean nothing if it cannot be viewed or used, Mattern warns. “New cloud-based software solutions, such as Synexio from Syntegon, provide a remedy by enabling the acquisition, evaluation, and visualization of equipment and production data,” he says. “[These solutions] allow for real-time monitoring of machine conditions, helping manufacturers make data-based decisions and optimize operations.”

“In sectors like pharmaceuticals, where regulatory compliance and precision are critical, automation ensures that products meet exacting standards,” continues Funaro. “Automated quality control systems, including automated visual inspection and process analytical technology (PAT), are reducing the risk of human error and ensuring that processes stay within defined limits.”

Reducing human intervention in processes is particularly helpful in high-risk environments, such as dealing with hazardous chemicals or highly potent ingredients, asserts Funaro.

“The use of robotics is taking the industry a huge step further towards even higher product protection and quality, as it eliminates the main cause for contamination (i.e., human intervention),” Mattern remarks. “This is further fueled by [the European Union’s] Annex 1 [guidance].”

In August 2023, the updated EU good manufacturing practice (GMP) Annex 1 guidance (1) came into operation (except for point 8.123), which has profound implications for sterile manufacturing across the global pharmaceutical sector, Mattern specifies. “One of the key challenges presented by the new Annex 1 is the requirement to separate the aseptic processing area from the operator’s environment. As a result, pharmaceutical manufacturers now need at least restricted access barrier systems (RABS) to gain approval for new products,” he says.

After the updated guidance was published, industry saw a surge in upgrades to existing cleanroom lines to incorporate RABS, Mattern notes. “Manufacturers must choose whether to upgrade their current cleanroom line for a new product or invest in new filling equipment with isolator technology or RABS,” he specifies.

“It is expected that isolator technology will become the new standard, given the added safety provided by automatic bio-decontamination processes and the pressure differential from the operator environment,” Mattern notes. “[Whereas], RABS will likely remain a preferred option for more frequent product changes and experienced operators.”

The second chapter of the revised Annex 1 guidance places a focus on automation and robotic systems, highlighting these as “Appropriate Technologies” (1), Mattern reveals. “These technologies aim to reduce, or even eliminate, the need for gloves and human intervention in barrier systems,” he says.

“Gloves pose several challenges, which are addressed in dedicated paragraphs of the [Annex 1] document,” Mattern continues. “For instance, during longer production campaigns, [gloves] must be tested in operation—a process that is difficult to achieve with current glove testing equipment without compromising the sterile environment. The shift toward gloveless systems, utilizing robotics for these tasks, is viewed as the ideal solution.”

There are several potential future trends that are set to impact processing equipment and pharmaceutical manufacturing in general, asserts
Funaro. “These trends are being driven by technological innovation, sustainability goals, and the need for enhanced efficiency, safety, and compliance,” she says.

Notably, automation and Industry 4.0 are set to shape the future, explains Funaro. For example, employing predictive maintenance to anticipate equipment failures before they happen, utilizing AI and robotics for fully autonomous processing systems, integrating advanced sensors and machine vision systems for greater precision and control, and analyzing vast amounts of data with ML and AI, she summarizes

“Future equipment will increasingly incorporate self-learning systems that can adjust their operation based on past performance data. This will enable greater flexibility and adaptability in production lines, particularly in industries that need to switch between different products or processes frequently,” says Funaro. “As demand for customization and flexibility grows, processing equipment will increasingly be designed with modularity in mind.”

“A persistent concern within the pharmaceutical industry and its suppliers is the need for more sustainable equipment and processes. Unfortunately, resource consumption in the sector continues to surpass that of many other industries,” stresses Mattern. “In response, drug manufacturers are intensifying efforts to reduce their carbon footprint, with the support of manufacturing companies offering services such as lifecycle assessments for their equipment.”

Adoption of more energy-efficient equipment and an overall reduction of environmental footprint is becoming a greater focus for manufacturers, confirms Funaro. “Recyclable and reusable components in machinery, as well as the use of environmentally friendly materials, are becoming more widespread,” she says.

“Given its longevity, equipment usually contributes to overall emissions over several decades,” remarks Mattern. “By continuously optimizing their machines and developing new, more energy-efficient solutions, equipment providers can help pharmaceutical manufacturing companies achieve their sustainability goals.”

“These future advances will fundamentally change how industries approach processing equipment, offering greater flexibility, efficiency, and sustainability while adapting to the needs of a rapidly evolving marketplace,” concludes Funaro.

1. EC. Annex 1 Manufacture of Sterile Medicinal Products. 

Felicity Thomas is associate editorial director for 

®
Vol. 48, No. 11
November 2024
Pages: 9–11

When referring to this article, please cite it as Thomas, F. Increasing Processing Flexibility to Meet Demand. 

Articles

Evolving industry demands are driving the need for greater flexibility and innovation in processing equipment for pharmaceutical manufacturing.

Increasing Processing Flexibility to Meet Demand

CPHI Milan 2024: Highlighting the Benefits of Integrated Services

When outsourced services are required, bio/pharmaceutical companies can take a more traditional approach, whereby they split their program up and use one or more contract development and manufacturing organizations (CDMOs) in addition to a separate contract research organization (CRO), or they can choose an integrated model. “[The term] ‘integrated services’ has multiple meanings,” specifies Kevin Li, MBA, chief marketing officer at BioDuro-Sundia.

Integrated services can be viewed as horizontal, in that a partner would provide services covering discovery to development and commercial manufacturing, Li notes. If you then look vertically, it is possible to also integrate the medicinal chemistry, biology, and drug metabolism and pharmacokinetics into the discovery phase and through development, he adds. “One side can handle both drug substance and drug product, and one side can handle the pre-formulation, formulation development, until commercial manufacturing, everything in one side,” Li says, “so that integrated solution can really help customers to accelerate their innovation through multiple benefits.”

Benefits of using an integrated solution include the convenience of material transfer among different teams, the information sharing, and the quality system, which can help to speed up the program timescale, Li explains. “One of the biggest benefits is [that it is] very simple to manage the vendors, because it's very difficult and time consuming to manage multiple vendors, and if you do integrate the program with one vendor through our integrated or dedicated project manager, that's much easier, simpler to manage the process to avoid any potential interruptions.”

Click above to listen to the full interview captured on the show floor at CPHI Milan

BioDuro-Sundia exhibited at CPHI Milan, which took place on Oct. 8–10, 2024.

Kevin Li, MBA, chief marketing officer at BioDuro-Sundia.

Kevin Li, MBA, is the chief marketing officer at BioDuro-Sundia, and has more than 15 years of industry experience. Prior to working at BioDuro-Sundia, Kevin led the global marketing and public relations teams across the US and China for the WuXi Chemistry division at WuXi AppTec. Additionally, Kevin led the global marketing efforts for the Oral Dose, Rx, and OTC Softgel business units at Catalent Pharma Solutions. Earlier still, Kevin worked in marketing for ConvaTec and Becton, Dickinson and Company, and held scientist roles at Pfizer (Hospira) and Abbott (AbbVie). Kevin studied chemistry at Northwestern University and business administration at Duke University.

Videos

Pharmaceutical Technology Europe chats with Kevin Li, MBA, from BioDuro-Sundia about integrated services and the benefits these services can provide to pharma companies.

Retrofitting Facilities for Cell and Gene Therapy Production

In his episode of Ask the Expert, Peter Walters, Fellow of Advanced Therapies at CRB Group, discusses the retrofitting of older and/or solid-dosage facilities into sustainable cell and gene therapy manufacturing facilities. According to Walters, cell and gene therapy facilities can be made very lean and sustainable, with some being 100% electric.“A lot of that has to do with the fact that there isn't a huge utility draw for that process,” says Walters. “A lot of those materials are going to be typically purchased and either made off site and brought in, or are made on site, but are low water usage, low utility usage.”

Walters says that, when retrofitting a facility, air handling, air locking, and personnel flows are factors to consider. “Cell therapy facilities tend to have at least a handful of spaces that want to be very high classified, and so you're [going to] need not only the air handling—ability to push a lot of air through those spaces in a very clean manner—but the air locking to get the material segregation movements [and] the personnel flows to get into those highly classified spaces. As we talk about gene therapy, sometimes viral vector spaces want to be BSL [biosafety level] spaces. They want to have certain levels of segregation. It's not uncommon to see vector facilities that have [a] two-corridor system; one dedicated to the supply of materials and one dedicated to outgoing waste and outgoing materials, and that helps drive segregation of flows and materials through your facility. It can be difficult to find a facility that's set up in such a way [as] to facilitate an easy retrofit.”

Click the video above to watch Walters answer the following question:

We wish to retrofit our solid-dosage facility into a sustainable facility for cell and gene therapy commercialization. What kind of cost should we expect?

Peter Walters is Fellow of Advanced Therapies at CRB Group.

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

, and it may appear in a future episode or print column.

In this episode of the Ask the Expert video series, Peter Walters, Fellow of Advanced Therapies at CRB Group, discusses how facilities used for solid dosage manufacturing may be retrofitted into sustainable cell and gene therapy production facilities.

Anil Andrade, vice-president of Global Sales at ACG World, shared insights about the growth in demand in the pharma industry and efforts put forth to achieve sustainable operations.

CPHI Milan 2024: Growth and Sustainability in the Pharma Industry

 sat with Anil Andrade, vice-president, Global Sales, ACG World, at CPHI Milan. Andrade discussed the changing perceptions of the pharmaceutical industry over the years and the importance of sustainability in pharmaceutical operations. Over the past 10–15 years, ACG has seen global growth in demand, and more so in Europe, North America, and Asia. Andrade also emphasized efforts to achieve sustainability, with the goal of making less of an impact on the environment as is possible.

One of the main reasons for global growth that Andrade sees is the COVID-19 pandemic. “There was more demand than supply. While everyone increased their capacity, customers saw that there were very few reliable suppliers who are there for the long term,” he noted. Another key factor impacting global demand are “the wars going on in different parts of the world,” which, according to Andrade, are causing transportation conflicts. “[S]hipping lanes are being disrupted, and that is … impacting our commitment to our customers,” he said.

In response, ACG has been investing in new capacity expansions in Europe. At a facility the company purchased in Croatia over 10 years ago, for example, the company has invested in infrastructure, technology, systems, and processes over the past five years, and has increased capacity in that plant by almost 80%.

Meanwhile, from a capsule-manufacturing point of view, sustainability is important. “Manufacturing capsules consumes a lot of water, and we have been trying to make our operations more efficient so that they consume less water, less paper, less plastic. In Croatia, as an example, we have reduced the paper consumption by almost 25 tons in a year. Same with plastic, we have reduced the consumption of plastic by 25 tons, and that has related to the benefits that we see going forward,” Andrade explained.

The company’s sustainability efforts also include reducing the amount of organic waste created by its manufacturing process. “The idea is that we want to be as less impactful on the environment as possible,” Andrade stated.

ACG exhibited at CPHI Milan, which took place in Milan, Italy, on Oct. 8–10, 2024.

Anil Andrade, Vice-President Global Sales, ACG

Anil Andrade is vice-president of global sales at ACG with experience in building and leading a sales organization, managing complex, multi-partner alliances, working directly with key decision makers, CEOs, and owners. As a key member of the leadership team reporting to the CEO and board, he is responsible for creating and executing strategic plans and nurturing strategic business ecosystems globally. He has profit and loss responsibility for multi-site manufacturing, with a focus on deeper market penetration, organic revenue growth, returns on capital, and sustainable competitive advantage. Andrade manages strategic sales initiatives to increase market share in developed and emerging markets through global team building, expansion of global manufacturing, talent management, and organizational culture.

Syringe, glass vials and stethoscope on mirror surface. Color toned | Image Credit: ©New Africa - stock.adobe.com

Suitable packaging for pharmaceutical products is a must to ensure the integrity of the products is maintained, which includes making sure the product does not degrade, become contaminated, or get damaged when being transported, for example. The role packaging plays in protecting drug products is important irrespective of dosage form or administration route; however, as the drug molecules themselves become more complex, packaging has also needed to advance.

Keeping up to date with the latest regulatory and pharmacopeial guidelines and revisions is always in the best interest of a pharmaceutical company throughout all aspects of its business. In terms of pharmaceutical packaging, there are important standards and guidelines for companies to follow, not only to ensure the safety and efficacy of the medicines housed within their packaging, but also to protect and assist the patient.

“Compliance trends in the pharmaceutical packaging sector are constantly evolving but CRSF [child-resistant senior-friendly] packaging has long been a major concern,” stresses Carole Grassi-Mircich, chief commercial marketing and innovation officer at SGD Pharma. “In the United States, over 300 children under the age of 20 are treated in the emergency department every day, and two die as a result of unintentional poisoning (1). And in the European Union, it is the fifth leading cause of accidental death for children and adolescents. Most cases occur within the home, when children gain access to harmful substances that are improperly stored.”

While the ultimate responsibility lies with parents or carers of children to ensure medications are not erroneously consumed, pharmaceutical packaging manufacturers are also being tasked with providing packaging solutions that are child-resistant while also being as user-friendly to adults and senior citizens as possible, Grassi-Mircich explains.

“There are numerous mechanisms for child-resistant closures (CRC) on medical packaging, which are primarily categorized into re-closable (bottles) or non-re-closable (blister packs),” Grassi-Mircich continues. “In some countries, pharmaceutical and healthcare companies are required by law to produce packaging that is child-resistant, while maintaining accessibility for the consumer.”

For example, Grassi-Mircich points out the standard test procedure, published by the International Organization for Standardization, for re-closable child-resistant packaging (2). And, in Europe, she notes, several norms have been introduced that complement the ISO standard.

“Pharmaceutical companies must have certification of child resistance for the for their full solution and the time and cost related to this is significant,” Grassi-Mircich stresses. “To streamline this, drug manufacturers can partner with packaging manufacturers that can not only supply innovative, high-quality packaging, but also provide the required certification (ISO 8317:2015 in Europe and 16 

1. ChildCare Aware of America. Poisoning. 

https://www.childcareaware.org/our-issues/crisis-and-disaster-resources/poison/

Child-Resistant Packaging—Requirements and Testing Procedures for Reclosable Packages

“With highly complex biologics and other specialty drugs representing an increasing proportion of the pharmaceutical market, demand for pre-sterilized and ready-to-use (RTU) drug packaging options has increased in recent years; valued at $8.42 billion in 2022 and predicted to reach $14.23 billion by 2031 (1),” says Carole Grassi-Mircich, chief commercial marketing and innovation officer at SGD Pharma. “As well as this, trends such as personalized treatments in place of blockbuster drugs, increasing regulatory quality and compliance and a move towards self-medication, are changing the way that drugs are administered and therefore manufactured.”

“As the drug pipeline becomes more complex with the rise of biologics and personalized medicine, sterile drug containment and delivery systems have emerged as a great solution,” explains Robert Lindner, global product manager for Bulk and Sterile Solutions at SCHOTT Pharma. “Both prefillable polymer syringes and RTU [ready-to-use] cartridges offer the versatility to handle a wide range of drug formulations. The ability to pre-fill syringes and cartridges in a sterile environment and their compatibility with various drug formulations make them indispensable for biologics and other complex therapies and reduce the risk of contamination.”

Made from either glass or advanced polymers, prefillable syringes are a convenient option for the end user and have become a cornerstone of modern drug packaging, asserts Nina Krautwurst, global product manager for Polymer Solutions at SCHOTT Pharma. “Polymer syringes offer the advantage of being shatterproof, significantly reducing the risk of breakage during handling. This is crucial for maintaining the integrity of sensitive biologics and high-value medications. The design of these syringes has evolved to ensure they are user-friendly and safe, making them ideal for both clinical and at-home use. Their compact and robust nature facilitates easy integration into secondary packaging solutions.”

Additionally, there have been advances made in secondary packaging for prefillable syringes to ensure safe transportation and storage, specifies Krautwurst. “Modern designs focus on maintaining the syringes in optimal condition and ready for use. This includes robust and compact packaging solutions that emphasize safety and compliance,” she says. “The secondary packaging is designed to be user-friendly, facilitating easy handling and reducing the risk of contamination.”

Pharmaceutical companies are moving toward RTU components as preferred solutions to meet the needs of the market and address challenges, concurs Grassi-Mircich. “And [pharmaceutical companies] are outsourcing their packaging to trusted experts who offer sterile and RTU options, [which,] in turn, has led pharmaceutical packaging manufacturers to invest in advanced packaging facilities to meet increased demand and ensure effective and timely product delivery,” he adds.

Grassi-Mircich also points out that for primary packaging of pharmaceuticals, glass provides significant benefits, including strong chemical and mechanical performance, and sustainability. “Based on the proven success of other RTU glass primary packaging solutions, RTU molded glass vials offer a new choice to pharmaceutical industries in aseptic manufacturing and processing,” she says.

“Molded glass brings its own improved chemical durability and greater mechanical strength, combined with proved industrial platforms for RTU primary packaging as well as state-of-the-art secondary packaging systems, such as trays and nest and tubs used in fill and finish,” Grassi-Mircich continues. “Secondary packaging removes glass-to-glass contact, improving the aseptic filling lines of pharmaceutical companies and reducing the risk of failure during drug manufacturing and development. The expansion of the pre-sterilized and RTU market has triggered renewed demand for secondary packaging systems that can easily incorporate RTU offerings.”

For RTU cartridges, particularly prior to the filling stage, secondary packaging developments have focused on sterility and protection, often incorporating sterile barrier systems such as nested tubs or trays, which maintain the integrity and cleanliness of the cartridges during transport and storage, confirms Lindner. “Modern secondary packaging solutions are optimized for automation, reducing manual handling and enhancing efficiency in high-throughput production lines. This [automation] minimizes contamination risks and streamlines the transition to the filling process, reflecting the industry’s focus on maintaining sterility while improving operational efficiency,” he says.

“Patient safety is paramount to pharmaceutical packaging manufacturers,” notes Grassi-Mircich. Additionally, it is important for packaging manufacturers, such as SGD Pharma, to ensure all products not only meet all relevant regulatory guidelines to ensure safety but also that any technological advances are also considered to improve the packaging for the patient, she states.

When looking at glass vials, for example, companies can use an internal siliconization treatment that provides advanced protection for drug products that are sensitive, aggressive, and viscous, Grassi-Mircich continues. “A micro-layer of silicone is highly bonded to the internal surface of the glass vials and acts as a barrier coating to provide dual protection: preventing ion leaching from the glass into the drug product as well as blocking drug molecules from penetrating the glass primary packaging. The internal coating enhances the functional performance of the glass vial while safeguarding the integrity of the sensitive therapeutic product to ensure it is preserved when it reaches the patient,” she adds.

“Patient safety has also been supported by the development of an external treatment on the sealing surface of glass vials that protect solid oral drug products from moisture and oxygen though a hermetic seal adhesion of the foil,” Grassi-Mircich specifies. “The vials are child-resistant senior-friendly (CRSF) compatible and have tamper-evident closures, both of which help prevent accidental ingestion.”

“Advances in drug packaging have played a crucial role in improving patient safety through several key innovations,” states Krautwurst. “Prefillable polymer syringes have significantly contributed to patient safety by offering features designed to reduce medication errors and improve the administration process. These syringes often come with tamper-evident closures, ensuring that the medication has not been compromised before use.”

Dosing errors are prevented through clear, easy-to-read labeling on the polymer syringes, which provides accurate information about the medication housed within, points out Krautwurst. “The design of these syringes allows for precise dosing, which is particularly important for administering potent biologics, ensuring that patients receive the correct amount of medication,” she says. “Additionally, using advanced polymer materials reduces the risk of contamination and particle generation, enhancing the overall safety profile of the drug.”

Another advancement in packaging, driven by the trend to large-volume subcutaneous injections, is that of specialized containers. These larger cartridges and prefilled syringes “have been developed to handle higher volumes of medication higher volumes of medication while maintaining drug stability and ensure patient comfort during administration,” remarks Lindner.

“Packaging often integrates with wearable devices, autoinjectors, or infusion pumps, enabling patients to self-administer larger doses safely and conveniently outside clinical settings,” adds Lindner. “This reduces the need for frequent hospital visits and allows for more consistent treatment adherence. Innovations in packaging have prioritized sterility and ease of use, essential for patient safety. Sterile packaging minimizes the risk of infection, while user-friendly designs help ensure patients can administer their medications correctly and comfortably. These advancements reflect a strong focus on improving patient outcomes and supporting the unique demands of complex therapies.”

Furthermore, leveraging innovative technologies to make packaging more interactive has the potential to improve overall health outcomes for patients, asserts Lindner. “These innovations can be incorporated into RTU containers’ packaging to give patients instant access to dosing instructions, reminders, and other critical information via their smartphones,” he says. “This enhanced connectivity fosters greater patient engagement and compliance, which is essential for effectively managing chronic conditions.”

While patient safety is obviously critical, other factors that can help make a product appealing to the patient must also not be overlooked. “During recent years, the demand for sustainability has accelerated throughout the packaging industry and has had a particular influence on the pharmaceutical industry,” notes Grassi-Mircich. “Consumers are now more environmentally conscious than ever before, and sustainability has become a key factor in their decision-making. In a recent survey (2), FEVE [The European Container Glass Federation] revealed that three out of four European consumers find that purchasing sustainable products makes a difference for our environment.”

Grassi-Mircich highlights that “glass is already a highly sustainable packaging material and is [now] 70% less energy intensive than 50 years ago (3). However, in response to growing consumer demand,” she continues, “the glass packaging industry is striving to improve this further, investing around €600 million [US$670 million] each year on updates to manufacturing facilities and steps in the supply chain to improve energy efficiency.”

“Sustainability has become a driving force in the evolution of drug packaging,” confirms Krautwurst. For syringes, polymer materials provide a lightweight option that require less energy to produce and transport than other materials, which can result in a lower carbon footprint, she remarks. Further, high durability of polymer syringes can lead to fewer breakages and hence less waste during handling and transportation, Krautwurst states.

“Drug packaging has also become more sustainable through efforts to reduce its ecological impact, such as using steam-sterilized RTU cartridges. Steam sterilization, which operates with ultrapure water and heat, requires lower energy levels for the same or better microbial kill rates than chemical or radiation-based sterilization techniques, reducing the overall carbon footprint,” says Lindner. “Additionally, steam sterilization does not produce harmful residues or by-products. Further innovations include using eco-friendly materials and designs that minimize waste and energy consumption.”

Along with an increased demand for greener practices from consumers, regulatory pressures and overall industry goals to lower carbon footprints are driving the shift towards sustainability, adds Lindner. “These advancements aim to balance effective sterilization with environmental responsibility, reflecting a broader commitment to sustainability in the pharmaceutical industry,” he concludes.

Pre-Sterilized/Ready to Use Pharmaceutical Packaging Market Size, Share and Trends Analysis Report by Type of Container (Sterile Cartridges, Sterile Syringes, and Sterile Vials), by Type of Closure (Caps, Plungers, Seals, Stoppers, Tip Caps/Needle Shields), by Material of Fabrication, Region, and Segment Forecasts, 2023-2031

FEVE. Sustainability and Climate-Neutral Production. 

feve.org/glass-industry-positions/sustainability-climate-neutral/

Glass Hallmark. Why Glass is Best for Pharmaceutical Packaging. 

®
Vol. 48, No. 10
October 2024
Pages: 10–14

When referring to this article, please cite it as Thomas, F. Out-of-the-Box Packaging Advancements. 

Pharmaceutical packaging must advance to adapt to new, complex modalities.

Out-of-the-Box Packaging Advancements

CPHI Milan 2024: Pharma Industry Growth and Investment

spoke with John McQuaid, president and managing director at Almac Pharma Services, at CPHI Milan 2024, held October 8–10, in Milan, Italy, about how the pharmaceutical industry is growing and what might drive investment in the future. McQuaid also discusses the demand for analytical services and the challenges to provide those services that contract development and manufacturing organizations (CDMOs) face.

“There's quite a diverse range of drivers at the moment, anything from the BIOSECURE Act in the [United States], geopolitical factors such as that, right through to technology needs for emerging modalities,” McQuaid said. “If I speak about pharmaceutical development, first, there's never been a larger number of molecules in clinical development, and we're certainly seeing that increasing demand. We've got demand in areas such as [highly] potent [APIs], [and] age-appropriate formulations, such as pediatrics. We've got poorly soluble compounds, and the need for technologies to address that. And then we've got personalized medicines, such as, … cell and gene therapies, which drive particular needs in areas such as fill/finish and cold chain requirements.”

Commercially, McQuaid sees the rise of glucagon-like peptide-1 (GLP-1) drugs as driving demand and supply chain concerns. Auto injectors are also in demand as device combinations are common, and therefore, a growing area of the market. “And then the feedback we're also getting from many of our clients is that small molecules and small-molecule pipelines are particularly strong and healthy at the moment, and that's driving demand as well.”

Almac is addressing some of these areas by investing in technologies such as mini tablets for pediatrics and spray drying for poorly soluble compounds. “We're investing in cold chain capabilities, both for the clinical phases and the commercial phases, and then we have peptide synthesis coming online early next year at our API plant in Craigavon, with small molecule expansion kicking in later next year, and then further program for larger-scale API manufacturing.”

Pharmaceutical Technology Europe spoke with John McQuaid, president and managing director at Almac Pharma Services, at CPHI Milan 2024, held October 8–10, in Milan, Italy, about how the pharmaceutical industry is growing and what might drive investment in the future.