Aligning mRNA Progress with Regulatory Streamlining

BioPharm Peer Exchange

Drug Solutions Podcast: 

Employing novel technologies and more patient-centric approaches

Integrating Strategies for Formulation Success

Delving into Biopharmaceutical Development and Manufacturing

Drug Digest: 

 Quality Considerations in Changing Excipient Providers

Ask the Expert

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

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On Oct. 14, 2024, the biopharmaceutical research company Chiesi Group announced the operational launch of its Biotech Center of Excellence in its home base of Parma, Italy (1). The company’s approximately €400 million (US$436 million) investment in the new, state-of-the-art facility is broken down into €120 million (US$131 million) to be devoted to infrastructure, with about €260 million (US$283 million) earmarked for materials, innovative technologies, skills development, and training, up to the year 2030.

Chiesi Group intends to provide integration of the entire supply chain with the new center, developing and producing monoclonal antibodies, enzymes, and other proteins, and combining those with research and industrial production capabilities (1). Enhanced efficiency, the company said, will better allow Chiesi Group to innovate and bring new treatments to market. This strategy aligns with European Union priorities regarding not only innovation, but also security and private R&D investment, according to the company.

"We inaugurate a center with a production site that projects us into a new path of care, allowing us to continue making a difference in serving people and families living with chronic diseases, especially rare diseases, with increasingly innovative technologies,” said Alessandro Chiesi, Chiesi Group chair, in a press release (1). “In a rapidly changing world, this facility will help generate new knowledge and skills, contributing to a national biotech supply chain that attracts and retains the best global talents.”

Technical activities at the new center currently involve more than 60 employees, and that number is projected to grow to more than 80 by the end of 2025, with allowances for an eventual workforce of as many as 200 specialists (1).

"At Chiesi, innovation is at the heart of everything we do,” added Chiesi Group CEO Giuseppe Accogli, in the press release. “The opening of our new Biotech Center marks a bold leap forward in our commitment to delivering groundbreaking therapies that truly transform patients' lives. This center will elevate our production capabilities to new heights and reinforce our dedication to driving innovation. More than that, it will empower us to forge powerful collaborations and push the boundaries of what's possible in patient[s’] care.”

Earlier in 2024, Chiesi Group signed an agreement with Karolinksa Institutet, a medical university in Solna, Sweden, intended to accelerate R&D initiatives for rare diseases, respiratory diseases, diseases of prematurity, and other specialty care indications (2). The Karolinska agreement followed the company’s $1.25 billion acquisition of Amryt Pharma, a commercial-stage biopharmaceutical company focused on rare diseases, in January 2023, and a partnership with US-based Aliada Therapeutics signed in August 2023 for the development of drug delivery systems (3,4).

1. Chiesi Group. Chiesi Group's New Biotech Center of Excellence Brings the Future of Medicine to Parma, Italy. Press Release. Oct. 14, 2024.
2. Chiesi Group. Chiesi Group Forges Alliance with Karolinska Institutet to Tackle Urgent Health Challenges. Press Release. May 14, 2024.
3. Amryt Pharma. Chiesi Farmaceutici S.p.A. to Acquire Amryt Pharma Plc. Press Release. Jan. 8, 2023.
4. Chiesi Group. Chiesi Global Rare Diseases Announces Co-Development Agreement with Aliada Therapeutics to Advance Blood-Brain Barrier-Crossing Platform Technology in Lysosomal Storage Disorders. Press Release. Aug. 15, 2023.

Articles

The design of the center prioritizes integration of the entire supply chain, with the end goals of accelerating product development and autonomous production capacity in alignment with EU priorities.

Chiesi Launches Biotech Center of Excellence in Parma, Italy

BioDuro-Sundia, a contract research, development, and manufacturing organization (CRDMO) headquartered in Irvine, Calif., announced on Oct. 2, 2024 the launch of its new Compound Management Center in the Shanghai Free-Trade Zone in China, at the company’s Waigaoqiao site (1). Waigaoqiao is one of seven BioDuro-Sundia sites spread across the United States and China, which according to the company employ a total workforce of more than 2000.

The new center is described by BioDuro-Sundia as state-of-the-art, designed to enhance the CRDMO’s capabilities in the field of drug discovery by allowing for the systematic storage, handling, and management of compounds (1). Customers, the company said, will be able to take advantage of secure storage, comprehensively tracked inventories updated in real time, and samples ready to be accessed quickly in the interest of speedy delivery.

Combining with already existing drug discovery services, the center will expedite R&D processes, reduce costs, and accelerate new therapy candidate discoveries (1).

“Our new Compound Management Center represents a significant step forward in our commitment to providing world-class drug discovery services,” said Armin Spura, PhD, CEO of BioDuro-Sundia, in the press release disseminated by the company on October 2 (1). “By integrating this cutting-edge compound management system with our drug discovery platform, we can offer our clients faster, more reliable solutions to bring their new drug candidates to market, benefiting patients around the world.”

A compound storage laboratory with real-time temperature and humidity control will have the ability to manage more than 400,000 compounds, either solid or liquid, according to BioDuro-Sundia (1). It is equipped with a liquid handling station for fully automated workflows, while sample management software tracks steps at every point of the lifecycle. Services able to be offered include storage, weighing, dissolution, plating, liquid chromatography–mass spectrometry (LC–MS) analysis, and distribution.

Almost a year ago, in November 2023, Shanghai was the beneficiary of more expansion in the industry, with MilliporeSigma, the US and Canada life science business of Merck KGaA of Darmstadt, Germany, announcing at that time that it was opening the second phase of a new biologics testing center (2). This added 1500 square meters of lab space—notably, MilliporeSigma’s first biosafety laboratories in the Chinese market—to a facility and campus that first opened in 2022.

And elsewhere in the realm of drug discovery, Evotec announced on July 10, 2024 that it had entered into a multi-year master research collaboration and option and license agreement with Pfizer, under the terms of which the two companies would first focus on early discovery research for potential therapeutics targeting metabolic and infectious diseases. That work is being carried out at Evotec’s sites in France, namely its Campus Curie in Toulouse (3).

1. BioDuro-Sundia. BioDuro-Sundia Launches New Compound Management Center, Strengthening Drug Discovery Services. Press Release. Oct. 2, 2024.
2. MilliporeSigma. Millipore Sigma Expands Newest Biologics Testing Center in Shanghai. Press Release. Nov. 21, 2023.
3. Evotec. Evotec and Pfizer Collaborate to Advance Drug Discovery in France. Press Release. July 10, 2024.

The global CRDMO said its clients would be able to expedite R&D processes, thereby reducing costs and potentially leading to accelerated discovery of new candidate therapies.

BioDuro-Sundia Bolsters Drug Discovery Services with New Center in Shanghai

Tech Transfer Considerations

® spoke with Ahmed Youssef, senior manager, USP Process Development at Ascend, to get his input on how tech transfer may be complicated when dealing with emerging therapies, such as antibody-drug conjugates, cell and gene therapies, and patient-centric treatments. Youssef pointed to timing as being key for technology transfer.

“It takes an innovator around 12 to 24 months to make a product ready, tech transfer it, [and] complete the safety studies for it,” says Youssef. “But there could be other solutions that could be offered in the background that could make this more efficient, faster, and more attractive to product developers.”

When it comes to sponsors and contract organizations working together to ensure a secure tech transfer, Youssef says the contract development and manufacturing organization (CDMO) should shoulder the responsibility. “A good CDMO [should] have structured communication, because communication is key … when you're talking to your business partner. We always build that in a more collaborative environment,” says Youssef. “[A CDMO needs] to protect the IP rights of their clients, their partners, as well as good documentation practices, in addition to a solid IT department. All of that gives the assurance to the security of the data and the security of the transfer information between the CDMO and their partner.”

Youssef also gave his insights on how sponsors can benefit when contractors offer end-to-end services. “If you mean by end-to-end, the whole process, you know, without the whole offering, from the start of plasmid manufacturing till commercial manufacturing of the batches, and then the fill and finish and release, understand that the advantage would be that you're running all of that under one MSA [master supply agreement], one big MSA,” said Youssef.

Click the video above to watch the interview.

Ahmed Youssef, senior manager, USP Process Development at Ascend, provides insight on tech transfer when developing and manufacturing emerging therapies and new modalities.

 is senior manager, Analytics, at Abzena.

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For the pharmaceutical industry, drug formulation is a cornerstone, crucial for converting bioactive molecules into effective, stable, and patient-friendly medications. This intricate process, pivotal in the drug development lifecycle, involves a delicate balance of scientific rigor and practical application. Formulation scientists not only need a profound understanding of the drug's properties, but also must navigate the many challenges of delivering the drug in a viable, patient-centric manner. Balancing these aspects—both scientific complexities and practical realities, like manufacturability and regulatory hurdles—is key to ensuring that drugs are not only effective, but also accessible and acceptable to patients.

Formulation begins with an in-depth understanding of a drug's physical and chemical attributes, focusing on enhancing solubility and stability. Poor solubility can result in subpar bioavailability, rendering the drug ineffective; hence, techniques such as particle size reduction, salt formation, and solubilizing excipients—inactive substances used as carriers for the active ingredients—are employed. Stability is ensured through methods like lyophilization (freeze-drying) and the use of stabilizing agents, preserving drug efficacy.

Furthermore, maintaining stability across different pH levels is vital, considering the body's varied pH environments. Strategies such as buffer systems, protective enteric coatings to drugs, and pH modifiers are crucial. To improve bioavailability, especially for drugs with limited aqueous solubility, lipid-based formulations and nanoemulsions are increasingly used. These approaches are essential to meet the diverse challenges posed by different delivery methods, ensuring drugs perform their intended function efficiently and safely.

Delivery methods and patient-centric approaches

The pharmaceutical industry recognizes the unique challenges presented by different delivery methods, such as ensuring the efficacy of oral dosage forms, the sterility of injectables, the absorption of topicals, and the inhalation efficiency of dry powders. These forms must be carefully developed to address the specific mode of delivery, while maximizing patient compliance and comfort.

Formulation scientists are increasingly tailoring drug formulations to meet the individualized needs of patients, including considerations for age, health condition, and preferences. This patient-centric approach can manifest in forms such as orally disintegrating tablets, which are typically easy-to-swallow, effervescent tablets for the elderly, or flavor-enhanced syrups for pediatric drugs, to ensure that personalized medicine extends beyond the active ingredients to the very form and function of the medication itself.

Effective drug formulation hinges on the early detection of drug instabilities, typically achieved through a series of rigorous stress tests. A step-by-step, comprehensive process enables performing of tests designed to predict and counter potential issues that can compromise a drug's solubility and stability. This proactive approach ensures the efficacy and safety of a new drug. Strategic decision-making in drug development is informed by the outcomes of these tests, guiding developers in refining the formulation process. By identifying formulation challenges early, potential setbacks in later stages of development can be avoided, which is essential for efficient and successful drug production.

This type of proactive approach involving early detection of potential instabilities is vital to ensure successful drug formulation. By exposing the drug to various conditions, such as high or low pH, heat, and intensified light exposure, scientists can assess how well the drug holds up. This early detection allows for adjustments to be made to the formulation before it progresses too far in the development process, potentially saving time, money, and resources.

The formulation of a drug is a complex process that involves multiple stages, each playing a crucial role in ensuring the safety, efficacy, and manufacturability of the final product to ensure that the target product profile is achieved. This journey begins with a thorough understanding of the drug's physicochemical properties and its compatibility with various excipients. Subsequent stages involve refining the formulation to address any potential challenges, optimizing it for manufacturing, and conducting extensive stability testing.

The stages of drug formulation from initial analysis to final optimization include:

manufacturing stress tests and analytics: assessing the drug's response to different stresses typically encountered during the manufacturing process

preformulation: evaluating the effects of pH and charge on the drug's solubility and stability, providing a foundation for subsequent formulation development

pre-manufacturing optimization: aligning the formulation with process development to ensure manufacturability and stability throughout the production process

extended stability testing: evaluating drug stability over a typical Phase I clinical trial duration, confirming the formulation's durability under various storage conditions

freeze-thaw stress: testing the formulation's resilience against freeze-thaw cycles, a critical consideration for formulations intended for long-term frozen storage.

Throughout this multistage process, close collaboration between formulation, manufacturing, and process development teams is essential to ensure that the drug is developed and manufactured consistently, and at scale. This collaboration involves discussing process designs, validating processes, and participating in continuous improvement initiatives. By working together, these teams can optimize formulation, leading to successful drug products.

Beyond the immediate impact on drug development, formulation has a far-reaching impact on the entire pharmaceutical industry. Advancements in drug formulation have significantly enhanced the stability of pharmaceuticals, leading to extended shelf lives. This has a ripple effect throughout the industry, particularly in logistics and inventory management. A longer shelf life reduces the need for frequent manufacturing cycles, which translates to cost savings and environmental benefits. Moreover, it ensures that patients have access to effective medications for extended periods, which is crucial in regions with limited access to regular pharmaceutical supplies.

Effective formulation plays a crucial role in broadening patient reach and ensuring compliance. By addressing issues such as solubility and palatability, medications become more patient-friendly and easier to administer. This, in turn, significantly impacts patient adherence to treatment regimens, which is particularly critical for chronic diseases that require long-term medication use. Improved formulations can also lead to the development of alternative drug delivery systems, such as transdermal patches or inhalers. These alternative delivery methods offer more options for patients who may have difficulties with traditional methods, making it easier for them to administer their medications correctly and consistently. Additionally, proper formulation can mitigate cold chain challenges by enhancing a drug's stability at a range of temperatures, reducing its reliance on strictly controlled storage conditions, making it more accessible to patients in underserved areas.

Efficient formulation strategies are also pertinent in streamlining the drug development process, leading to reduced costs and faster market entry. By identifying and addressing formulation challenges early in the development pathway, pharmaceutical companies can prevent costly late-stage failures. This efficiency not only translates to reduced development costs for the companies, but also accelerates the availability of new treatments to patients, who are eager to access lifesaving or life-altering medications.

Future trends and innovation in drug formulation

The field of drug formulation is constantly evolving, driven by advancements in technology and scientific knowledge. These ongoing advancements are influencing medicine and healthcare in many ways, from enabling the development of more effective and targeted therapies to improving patient accessibility and adherence.

Formulation advancements are also playing pivotal roles in the development of personalized medicine. By tailoring the formulation to the individual patient's needs, clinicians can optimize drug delivery and efficacy, resulting in better treatment outcomes. For example, nanoscale drug delivery systems can be engineered to encapsulate drugs and target them to specific cell types or tissues. Formulation advancements can also enable the development of new drugs that are otherwise difficult or impossible to deliver using conventional methods. For example, formulation scientists have developed innovative ways to deliver highly potent drugs and biologics, such as monoclonal antibodies and antibody-drug conjugates, which are notoriously challenging to formulate.

Formulation innovation is also essential for the development of combination therapies. These therapies combine two or more drugs to achieve a synergistic effect, resulting in improved efficacy and reduced side effects. Formulators are critical to developing formulations that are compatible with each other and can be delivered safely and effectively in combination.

As the field of medicine continues to evolve, the importance of drug formulation will only grow. With the increasing development of complex and targeted therapies, formulation scientists will play even more critical roles in ensuring that these therapies are delivered safely and effectively to patients.

For the pharmaceutical industry, drug formulation is a cornerstone, crucial for converting bioactive molecules into effective, stable, and patient-friendly medications.

Navigating the Complexities of Drug Formulation

Feliza Mirasol is the science editor for 

On Oct. 9, 2024, Evonik announced that it has won the 2024 CPHI Excellence in Pharma Award in the “Sustainability” category for its plant-based squalene, PhytoSquene, an adjuvant that can be used for parenteral drug delivery applications. According to a company press release, the product is the first plant-based squalene on the market that complies with good manufacturing practices (GMP).

Vaccines such as the H1N1 influenza vaccine use squalene as an adjuvant. Adding it to vaccines stimulates the body’s immune response to the active ingredient. Pharmaceutical-grade squalene is currently sourced from shark liver oil, however, which runs the risk of depleting shark populations and negatively impacting marine biodiversity, Evonik stated in its press release. “In terms of quality, animal-derived squalene may be susceptible to batch-to-batch inconsistencies which can complicate regulatory processes. Some patients also cannot use animal-based products for cultural or religious reasons,” the company also stated in the release.

PhytoSquene belongs to Evonik’s Next Generation Solutions (NGS) portfolio, in which products are categorized by a distinct sustainability profile. Evonik’s Health Care business unit aims to transform more than 70% of its portfolio by revenue to NGS by 2030. This goal also includes commitments from the company’s life sciences division, Nutrition & Care, to reduce the need for animal-derived products while growing its biosolutions portfolio, according to the company.

“Sustainability drives us! This award confirms that we are pursuing the right goals: to offer our customers alternatives that enhance patient outcomes and protect our planet,” said Yann d'Hervé, head of the Health Care business line at Evonik, in the press release.

PhytoSquene is manufactured in Germany using a proprietary process. It comes from amaranth (

) oil. Amaranth is an herbaceous plant cultivated in many parts of the world, making it a renewable feedstock. The manufacturing process produces consistent quality and is compliant with 

 regulations. Evonik launched commercial-scale PhytoSquene in 2023.

In 2022, Evonik won a CPHI Pharma Award in the category “Packaging and Drug Delivery” for a polymer-based messenger RNA (mRNA) drug delivery system. The drug delivery system is also used for delivery of other nucleic acid-based therapeutics.

Evonik also announced that it is transforming its Health Care business to focus on strategic core growth areas. Under the restructuring, Evonik will evaluate strategic options, such as partnerships or divestment, to develop its keto and pharma amino acid production sites in Ham, France, and Wuming, China. The company also plans to discontinue its production of keto acids in Hanau, Germany by the end of 2025 (1).

Evonik’s Nutrition & Care, the Health Care business within the company’s life sciences division, is transforming into a system solutions provider and is growing in core areas of expertise, including complex and highly potent APIs, oral and injectable drug delivery, and precision biosolutions, such as lipids for mRNA and gene delivery, and cell culture ingredients. The company described system solutions as tailored offerings that integrate products, technologies, and services with sustainability benefits, according to an Oct. 11, 2024 company press release (1).

For the full list of the 2024 CPHI Excellence in Pharma Awards winners, read the 

1. Evonik. Evonik to Restructure Its Keto and Pharma Amino Acid Business. Press Release. Oct. 11, 2024.

Evonik won the CPHI Excellence in Pharma Award in the “Sustainability” category in recognition of its plant-based squalene, PhytoSquene, used in parenteral drug delivery applications.

Evonik Wins Award at CPHI Milan for Plant-based Parenteral Drug Delivery Adjuvant

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The California-based contract development and manufacturing organization (CDMO) SK pharmteco, which focuses on small molecules and advanced therapies, announced on Oct. 2, 2024 that it was entering into a multi-year agreement with the German biotechnology company AaviGen to be the preferred manufacturing partner for AaviGen’s lead gene therapy product, AVG-101 (1).

According to a press release from SK pharmteco, AVG-101 is intended for the treatment of heart failure; AaviGen’s business specializes in the preclinical stage, and the company is a developer of curative gene therapies for both cardiovascular and cardiopulmonary diseases (1).

"SK pharmteco stands out from the global pool of suppliers because of its extensive experience in process development and manufacturing of adeno-associated viral-based gene therapies,” Martin Busch, PhD, COO of AaviGen, said in the press release. “Additionally, their recent investments in expanding manufacturing capacity provide us with exceptional support from the earliest stages of development to the commercial phase, especially for common cardiac disorders, such as chronic heart failure."

“We are thrilled to partner with AaviGen on their innovative gene therapy for heart failure,” added Patrick Mahieux, SK pharmteco president of cell and gene, Europe. “Our deep expertise in viral vector manufacturing and our commitment to quality and efficiency make us the ideal partner to support the development and commercialization of this promising therapy. We look forward to contributing to the advancement of this groundbreaking treatment for patients in need.”

In the press release, AaviGen’s proprietary adeno-associated viral vector technology was described as being able to enable development of therapies to target, and reverse, underlying molecular causes of heart muscle dysfunction, by concentrating on areas such as cardioprotection, contractility, and energy metabolism (1).

AaviGen has been around just since 2019, while SK pharmteco is a subsidiary of SK Inc., the strategic investment company of SK Group, which the press release identified as the second-largest conglomerate in South Korea (1).

"SK pharmteco is a key partner for AaviGen as part of our strategy to develop and commercialize innovative gene therapies against diseases of the cardiovascular and cardiovascular system,” said Patrick Most, AaviGen CEO, in the press release. “The SK pharmteco team offered the trust, competence, and understanding of how a young company like AaviGen must operate in a dynamic market from the first minute of our interactions. We look forward to the collaboration with great confidence."

In late September 2024, SK pharmteco announced another partnership, that with the supply-chain service company, Cryoport (2). The two businesses will work together to provide biopharmaceutical companies with integrated logistics and manufacturing services—such as end-to-end cell and gene therapy services that include biomaterial collection, bioservices, data solutions, and shipping systems.

1. SK pharmteco. SK pharmteco and AaviGen Announce Strategic Partnership to Manufacture AaviGen’s Lead Gene Therapy Product for Heart Failure. Press Release. Oct. 2, 2024.
2. SK pharmteco. SK pharmteco and Cryoport Partner for Cell and Gene Therapy Logistics and BioServices. Press Release. Sept. 25, 2024.

SK pharmteco will be the preferred manufacturing partner for AVG-101, AaviGen’s lead gene therapy product.

AaviGen, SK pharmteco Announce Manufacturing Agreement for Heart Failure Gene Therapy

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The European Medicines Agency (EMA) and the Heads of Medicines Agency (HMA) announced that the draft joint strategy for the European Union to 2028 (EMANS 2028) is now open for public consultation. The consultation period will be open until Nov. 30, 2024.

 has been reviewed and updated as regulatory and technical situations have changed rapidly (1). New regulations (e.g., legislation to address public health emergencies and reform of the EU medicines regulations) and technical advances, such as the use of artificial intelligence (AI), have spurred the changes to the original strategy.

“Since EMANS 2025, the availability and use of AI have become more commonplace, and the network aims to harness the full potential of AI across all the EMANS focus areas. The use of digital technology and AI has the potential to transform the network’s core work of evaluating human and veterinary medicines for authorization and monitoring their safety through the EU’s pharmacovigilance system. For veterinary medicines, the network will also push ahead with its vision to implement new digital solutions in its European Veterinary Big Data strategy,” the strategy document states (1).

The strategy to 2028 will focus on creating pathways to medicines in the EU. There is also a plan to find ways to leverage data, digitalization, and AI to improve processes.Innovation and competitiveness are priorities that will be nurtured through a regulatory science and research environment, according to EMA. Strengthening the supply chain and the sustainability of the EU network are also on the agenda. Each focus area will be evaluated by EMA and HMA to assess progress and adapt approaches, if necessary.

“The six focus areas have been carefully chosen to support the network’s core work of evaluating medicines as we take strides to promote the development of medicines and ensure that they reach those who need them,” said Maria Lamas, chair of the HMA Management Group, in a press release (2).

“The overarching theme of our updated strategy to 2028 is that of change—rapid, somewhat unpredictable, but nonetheless full of promise,” said Emer Cooke, EMA executive director, in the press release (2). “It will guide the network as it seizes opportunities and meets the challenges of the near future, including preparing for and responding to public health emergencies and threats such as antimicrobial resistance. Now is the time to share your views and help shape the direction of the network for the next few years.”

Stakeholders may provide input through an online questionnaire until Nov. 30, 2024. [https://ec.europa.eu/eusurvey/runner/EMANS2028publicconsultation] The strategy will be finalized after the consultation period and be implemented through multi-annual workplans. The final strategy is expected to be adopted by March 2025.

“While EMANS 2028 cannot preempt the legislative changes or predict the future, this strategy will prepare the network for the revisions to the pharmaceutical legislation and further changes to the technological and regulatory landscape,” Cooke says in the document’s introduction.

Seizing Opportunities in a Changing Medicines Landscape, The European Medicines Agency Network Strategy 2028 (draft)

EMA. Seizing Opportunities in a Changing Medicines Landscape. Press Release. Oct. 9, 2024. 

The draft joint network strategy for the EU until 2028 will be open for public consultation until Nov. 30, 2024.

EMA and HMA Publish Network Strategy for Public Consultation

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

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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 Olivier Rousseau, CEO, 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, Rousseau 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),” Rousseau 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, Rousseau points out the standard test procedure, published by the International Organization for Standardization, for re-closable child-resistant packaging (2). And, in Europe, he 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,” Rousseau 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 Olivier Rousseau, CEO, 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 Rousseau. “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.

Rousseau 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,” he 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,” Rousseau 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 Rousseau. 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, he 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, Rousseau 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,” he 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,” Rousseau 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 Rousseau. “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.”

Rousseau 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,” he 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. 

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.”

Videos

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.

Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Experts in cell and gene therapy weigh in on hot topics in a quick-hitting buy, sell, hold format before expanding their thoughts on complex questions. 

Buy, Sell, Hold: Cell and Gene Therapy

 is a rapid-fire expert panel covering a single topic, such as lipid nanoparticle delivery, supply chain resilience, 

 (CGT), or aseptic filling. Panelists first respond to quick-hit questions with a buy, sell, hold format before being allotted more time to share more considerate responses to complex topics.

While finance and investment perspectives flavor the discussion, science and pragmatism are the main ingredients driving these dynamic panel discussions.

“Episode 1: Cell and Gene Therapy” features the expertise of Dr. Fabian Gerlinghaus, co-founder and chief executive officer of Cellares; Dr. Claudia Zylberberg, board chair and co-founder of Arscience Biotherapeutics, and board chair and co-founder of Akron Biosciences; and Benjamin McLeod, director, Cell & Gene Therapy Segment, at NanoMosaic.

In the first 2 segments, the panelists share quick thoughts on CGT topics, including: The merits of focusing on orphan diseases; training new staff versus re-training existing staff; machine learning, artificial intelligence, and quantum computing; existing supply chain functioning; government investment into CGT; using traditional CDMOs for CGT production; facility retrofits for CGT; and CGTs as first-line treatment.

In the final segment, panelists had up to two minutes each to weigh the advantages and disadvantages of gene editing (CRISPR), gene augmentation, and gene-silencing approaches. Panelists also discussed their technology or engineering wish lists, as well as how to best to sync up regulations to current technology progress. Lastly, they exchanged ideas about the key missing piece(s) to lowering cost and improving accessibility.

Click here for more episodes of Buy, Sell, Hold

Dr. Fabian Gerlinghaus, Co-Founder and CEO, Cellares

Fabian Gerlinghaus is Co-Founder and Chief Executive Officer of Cellares. He is driven by a strong sense of purpose and is passionate about building the future of cell therapy manufacturing. With 10+ years of experience as an innovator and a leader, Fabian has established a track record of assembling top-performing teams to successfully drive novel bioprocessing technologies from ideation to commercial readiness. Prior to co-founding Cellares, Fabian served as Chief Innovation Officer at Synthego, where he co-invented the company’s proprietary RNA synthesizer technology and helped grow the company from five to more than 230 employees. He successfully led the interdisciplinary team that took synthesizer technology from whiteboard sketch to production-ready instruments within two years, enabling the company to be the first to market with its CRISPR/Cas9 product portfolio. He earned a master’s degree in aerospace engineering from the Technical University of Munich, and an honors degree in technology management from the Center for Digital Technology and Management, Munich

Dr. Claudia Zylberberg, Board Chair and Co-Founder Arscience Biotherapeutics, Board Chair and Co-Founder Akron Biosciences

With over 30 years of experience in the regenerative medicine industry, Dr. Zylberberg has established herself as a leader in her field. For nearly 15 years, she led Akron Bio as its founder and CEO with leadership, foresight, and expertise in advanced therapies manufacturing. Her passion for pushing the industry forward in the development and commercialization of safe novel therapies also led her to co-found the Standards Coordinating Body and serve as an active member of numerous industry boards and advisory committees. Claudia co-founded AssureImmune, an adult stem cell bank, and worked with Nabi Pharmaceuticals, specializing in human plasma-derived products. Her experience in product development and protein manufacturing was instrumental in the development of key materials to accelerate the regenerative medicine industry. She holds numerous patents and developed several patent-pending platform technologies in cryopreservation, novel formulations, and others. Claudia received her PhD from the University of Buenos Aires, where she studied Immunology, and conducted her doctoral research at the University of British Columbia. She also authored a children’s book called You’re Full of Genes to introduce the younger generation to genetics. Claudia is a member of the Forum on Regenerative Medicine at the National Academies of Sciences, Engineering, and Medicine.

Benjamin McLeod, Director, Cell & Gene Therapy Segment, NanoMosaic

Currently Benjamin helps many related researchers become more familiar with CGT concepts by translating complex processes into digestible bites on social media platforms such as LinkedIn and X. At OmniaBio he was product manager, collaborating with technical stakeholders to develop clear and actionable messaging around OmniaBio’s manufacturing services. At Virica Biotech he was Technical Lead, for a company whose viral sensitizer technology, increased viral yield in manufacturing, and potency in viral therapeutic products.

In episode 1, cell and gene therapy experts Dr. Fabian Gerlinghaus, Dr. Claudia Zylberberg, and Benjamin McLeod weigh in on hot topics in CGT. 

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