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

Felicity Thomas

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.

Videos

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. 

Felicity Thomas is associate editorial director for 

®
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. 

Articles

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.

On the final day of CPHI Milan 2024, Oct. 10, 2024, a panel brought together by Fujifilm Diosynth Biotechnologies debated the numerous paths to “Building the Future Pharma Workforce” (1,2). Moderated by Pushpa Vijayaraghavan, healthcare practice lead at Sathguru Management Consultants, the other contributing panelists were Nagarjun Chakilam, director of Maithri Drugs; Jakub Knurek, business development specialist at Mabion; Morgan Rex, senior quality engineer at ApiJect; and Megan Smyth, senior team leader at Almac Group.

“There's two significant changes that I've really seen in my nine years of being in the industry so far,” Rex said. “The first is that there's a general trend, and this is really relevant in the United States, to bring healthcare out of the hospital in[to] the clinic and bring it directly to the patient as much as possible. And that trend is being driven by this desire to decrease the cost of healthcare while also increasing the access to healthcare, which will increase the adherence of patients to their medicine, which will improve vaccine accessibility—and so that's what we're seeing in the developed world, and … we're creating different formats for drug delivery and injections.”

Accelerating these changes in the industry have been some necessary adjustments in workflow and, in tandem, newly forged technologies resulting from the COVID-19 pandemic.

“So, the way it impacted us is, you know, [to] think about digitizing all the quality processes,” Chakilam said. In the past, quality processes were manual and siloed, according to Chakilam. “But now for us to embrace these new technologies, what we thought was it is more crucial and more important to digitize them first, and not just digitization like transforming from paper to screen or just doing something on the computer, but we want to have all those systems integrated in the back end as well.” Chakilam suggested technology trends be embraced and for the industry to move to implement flow chemistry once digitalization is completed. “Maybe at that point it will be a little bit more easier and more effective.”

“We're really excited about how we can unleash the power of AI [artificial intelligence] in our roles, in our organizations and our industry,” moderator Vijayaraghavan added. “How do we get our human capital, the security that there is still a people-driven future here? And how should people think of staying ahead of this curve and not feeling threatened by it, but, you know, being part of [the] revolution?”

Discussing the rise of women in leadership positions in the pharmaceutical industry, Vijayaraghavan made light of the expert panel consisting of more women than men, a point that was then elaborated on by Knurek.

“In every gender, [to] have that passion for biotech, for improvement that's really challengeable for all companies, how we can search, I think, more about headhunting, talent acquisition from that perspective?” he said.

In any case, Smyth said, the industry is expanding, and job recruitment is hearty. “There's just so many opportunities to be able to do so much in this industry. And you know, we've been building our capabilities towards manufacturing, and yeah, I think I'm really excited,” she said. “It's not going to be without its challenges, because we're doing a lot of these things for the first time, and it's exciting to be an innovator, but it's also going to have the challenges that need to be problem solved. And I think ultimately that's why most of us are in this industry, to be able to improve it and make it better.”

1. Vijayaraghavan, P.; Smyth, M.; Chakilam, N.; Rex, M.; and Knurek, J. Building the Future Pharma Workforce. Presentation at CPHI Milan 2024, Milan, Italy, Oct. 10, 2024.
2. CPHI Milan, Conference Agenda. cphi.com/europe/en/whats-on/agenda (accessed Oct. 10, 2024).

Five speakers discussed the impact of the COVID-19 pandemic, the rise of artificial intelligence, more women in leadership tracks in the industry, and various emerging technologies.

CPHI Milan 2024: What Does the Future Pharma Workforce Look Like?

CPHI Milan 2024: Evolution of Coating Design

 Europe spoke with Ali Rajabi-Siahboomi, vice president and chief innovation officer at Colorcon, about the evolution of coating design and how it has impacted investment, as well as innovations in packaging for oral solid dosage products.

Coating design for solid dosage products has evolved from sugar coating to film coating to solvent-based and then to aqueous coating over the years, according to Rajabi-Siahboomi. “But the development of this robust and optimized formulation that we've had, and the umbrella of the Opadry system, has made it much easier to have the right film coating, but at the same time, apply it much more efficiently,” he says. 

The functionalities of film coating have changed over the years as well, according to Rajabi-Siahboomi. “Many years ago, [film coating] was just more for adding color and recognizing different dosages and different product. Nowadays, we apply functionalities [such as] moisture barrier … putting tags in those film coating so that we can identify them as part of authentication and counterfeiting, anti-counterfeiting. So, there has been a whole evolution, but when we talk about some of these challenges, … it highlights the need for continuously focusing on innovating, bringing continuous improvement and innovation in this field.”

Click the above video to watch the full interview.

 is being held from Oct. 8–10, 2024 in Milan, Italy.

Ali Rajabi-Siahboomi is the vice-president and chief innovation officer at Colorcon, based at the Global Headquarters, USA. Rajabi-Siahboomi has held various academic positions in Nottingham and Liverpool JM Universities in the United Kingdom before joining Colorcon as technical director, responsible for Europe, the Middle East, and Africa, in 2000. His main research interests are solid dosage form pharmaceutics, pharmaceutical technology with emphasis on oral drug delivery systems, solubility enhancement to improve bioavailability, and consistency of drugs and bioequivalence formulations. He has published more than 300 articles, book chapters, abstracts, and patents and obtained his B.Pharm. and PhD in pharmacy from the University of Nottingham (UK).

Pharmaceutical Technology Europe spoke with Ali Rajabi-Siahboomi, vice president and chief innovation officer at Colorcon, about the evolution of coating design and how it has impacted investment, as well as innovations in packaging for oral solid dosage products.