Feliza Mirasol is the science editor for 

Feliza Mirasol

Sweden-based biotech company, Cellevate, which specializes in developing next-generation cell culture systems, announced on Oct. 3, 2024 that it is ready to pre-launch its nanofiber microcarriers for viral vector manufacturing in gene therapy production at CPHI Milan, occurring Oct. 8–10, 2024 in Milan, Italy. According to a company press release, these nanofiber microcarriers are the first to be available on the world market.

The nanofiber microcarriers, marketed as Cellevat3d, are designed to provide up to 60 times more surface area for cell growth than conventional systems, increasing yield and productivity in upstream bioprocessing of gene therapy applications. The microcarriers are engineered for stirred-tank bioreactors and support a wide range of upstream bioprocessing applications in addition to gene therapy, including pluripotent stem cell (PSC) expansion, organoid formation, human embryo kidney (HEK)-based recombinant proteins, and HEK-based vaccine production.

“Scalable, sustainable, and single use, Cellevat3d nanofiber microcarriers closely mimic the human extracellular environment, providing higher cell densities and enhancing yield for viral vector production compared to current standard microcarriers based processes,” said Laura Chirica, PhD, CEO, Cellevate, in the press release.

The company will make Cellevat3d nanofiber microcarriers available for pre-order at CPHI Milan. The product’s official commercial launch is slated for the upcoming BIO-Europe in Stockholm, Sweden, on Nov. 4–6, 2024.

“Our nanofiber microcarriers effectively address the key challenges of low productivity and high manufacturing costs facing the industry. With this pre-launch of Cellevat3d nanofiber microcarriers starter pack at CPHI Milan, we’re excited to provide early access to a completely new category of cell culture systems currently unavailable on the market. Cellevat3d nanofiber-based cell culture systems truly have the potential to transform biomanufacturing for advanced therapies and take a significant step toward making these therapies more accessible to patients,” Chirica said in the press release.

The Cellevat3d technology is a green and sustainable technology innovation, according to the company. The platform allows for industrial-scale production of nanofiber microcarriers—with significantly enhanced surface area for cell growth, reproducibility, customization, and scalability. The company expects these advantages will ultimately lead to an improved biomanufacturing productivity and process economy.

Safety concerns over virus-based vectors are driving investigative attention toward nanotechnology-based non-viral vectors. However, challenges around low transfection rates with nanotech-based non-viral vectors and their poor tissue-targeting ability need to be addressed. Current research suggests that nanocarriers such as non-viral vectors may have a critical role in enhancing gene therapy delivery, especially in the field of pulmonary disease therapy (1). In addition, other non-viral nanocarriers are being investigated as drug delivery systems, including organic-based nanoparticles—such as cellulose, collagen, silk-like polymers, elastin-like protein, silk-elastin-like protein—and inorganic-based nanoparticles (2).

1. Wang, H.; Qin, L.; Zhang, X.; Guan, J.; Mao, S. Mechanisms and Challenges of Nanocarriers as Non-Viral Vectors of Therapeutic Genes for Enhanced Pulmonary Delivery. 

, 970–993. DOI: 10.1016/j.jconrel.2022.10.061
2. Hajebi, S.; Yousefiasl, S.; Rahimmanesh, I.; et al. Genetically Engineered Viral Vectors and Organic-Based Non-Viral Nanocarriers for Drug Delivery Applications. 

 (20), 2201583. DOI: 10.1002/adhm.202201583

Articles

The nanofiber microcarriers are the first of their kind for manufacturing viral vectors used in gene therapy production, according to Cellevate.

Cellevate Plans Pre-Launch of First Nanofiber Microcarriers for Viral Vector Manufacturing at CPHI Milan

On Oct. 1, 2024, SGD Pharma, a global provider of pharmaceutical glass packaging solutions, announced that it plans to exhibit an innovative range of products and services at CPHI Milan in Milan, Italy, from Oct. 8–10. As part of its exhibition, the company will introduce its siliconized molded glass vials. The company’s siliconization process is an internal treatment that provides additional functionalities to a glass vial, according to a company press release.

The internal silicon coating provides protection for sensitive, aggressive, and viscous drug products. In doing so, the coating reduces interactionwiththepackagingandpreservesdrugproductintegrity, according to the press release. SGD stated in the release that siliconizationisavailable for all glass types and for vials ranging in size from 3 mL to 500 mL, both clear and amber glass. The siliconization processissuited toallroutesofadministration, including parenteral,oral, andnasal administration.

“SGDPharma’s €5 million [US$5.5 million] investment in the siliconization production line at its state-of-the-art Saint-Quentin Lamotte(SQLM)plant [in France]enablescustomerstoreceiveordersofhigh-performancevialsatspeed meeting global demand,” the company stated in its press release.

The growing demand for the approval of biologics as well as new therapeutic approaches and the development of specialty drugs is driving the need for ready-to-use (RTU) packaging, SGD Pharma said in its press release. The company offers a RTU solution in molded glass, which includes its Sterinity EZ-fillvials (aregisteredtrademarkofStevanatoGroupand/oritsaffiliatesinoneormorejurisdictions). The Sterinity EZ-fillvials are designed for the rigorous requirements demanded by the pharmaceutical industry. The increased quality and flexibility of these vials enable the shortening of time-to-market and reduce total cost of ownership, according to the press release. Sterinity is suitable for various applications in veterinary and human health.

“AtCPHI2024,weareshowcasingsolutions developedwithourpharmaandveterinarycustomers’needsinmind,aimedatenablingthem tobringtheirdrugstomarketquicklyandsafely.Thiscommitmenttoinnovationisreflectedby our dedication to sustainability, which is an integral component of our company strategy. As we support theUNGlobalCompact forthefifthconsecutiveyear, we are particularlyproudof our progress in reducing carbon emissions at our global glass manufacturing sites,” said OlivierRousseau,CEO,SGDPharma,in the release. “SGD Pharma’s renewable energy initiatives, including the upgrade of our furnace at Saint Quentin Lamotte (SQLM) in France and the installation of solar panels at our Vemula, India, plant, underscore an overarching focus on decarbonization with the company-wide goal to cut emissions recorded in 2020, by 35% by 2030, and by 65% by 2040. These efforts reflect our responsibility to our customers, partners and the planet as we strive for a safer and healthier environment.”

The company will present an extension to its Sterinity range at CPHI, including the debut of aRTUTypeIImoldedglassvial. Sterinity RTU in Type II is expected to initially be available in size 10H, and an extendedrangeofsizes is expectedto launch during2025. SterinityTypeIiscurrently available in sizes 10 mL, 20 mL, 25 mL, 50 mL, and 100 mL. Type I is available in both clear and amber glass.

In addition, SGD Pharma will present an extension to its IDENCY range that includes 20 mL and 6 mL sizes. The company will also introduce new caps for its Ensiemo syrup bottles. The presentation will include the following:

IDENCY, a Type I glass vial that combines the benefits of both molded and tubular technologies, for parenteral sensitive drugs.

Ensiemofull packaging solution, apharma-grade TypeIII glass vialand pipette, which is now available with polypropylene or polyethylene caps for a tamper evident and child resistant closure.

The company now offers LabServices, an analytical testing service in molded glass for its customersandpartners (1). Through this service, experts at SGD Pharma’s SQLM plant provide analytical testing for pharma and biopharma companies, contract manufacturing organization and contract development and manufacturing organizations, and other glass manufacturers. The company expects to launch more LabServices in 2025.

The showcase will be held at SGD Pharma’s booth, 20B11, during CPHI.

1. SGD Pharma. New Labservices for Pharmaceutical Molded and Tubular Glass, Available Exclusively to SGD Pharma Customers and Partners. 

As part of a range of sustainable products and services that SGD Pharma plans to showcase at CPHI Milan, the company will introduce its siliconized molded glass vials.

SGD Pharma to Introduce Siliconized Molded Glass Vials at CPHI Milan to Showcase Sustainable Packaging

On Sept. 27, 2024, CPHI Milan announced survey results showing that growth in the contract services sector is expected to accelerate in 2025. The predictions come from new research findings from 280 pharmaceutical companies that are to be released at CPHI Milan as part of the CPHI Annual Report and Survey. In addition to suggesting accelerated growth for contract development and manufacturing organizations (CDMOs) next year, the research findings suggest that the industry does not feel favorable toward the recently passed BIOSECURE bill (1).

CPHI Milan noted in a press release that most analysts assessed the first half of 2024 as having slower-than-expected recovery. The press release quoted Gil Roth, president of the Pharma & Biopharma Outsourcing Association (PBOA), as having said, “While reports indicate that dollars are flowing back to late-stage assets [at CDMOs], there is little evidence that early stage pipeline products are receiving funding [yet]. This means that the lifeblood of CDMOs—projects moving through the development pipeline and smaller customers sticking with key service providers—remains hobbled.”

In the upcoming 2024 CPHI annual report, the organization takes note that the wider pharma industry is more optimistic with a forward-looking outlook for contract services companies’ growth in the next 18 months. The report shows that 49% of industry respondents are “highly positive” and 44% are “neutral”, while only 7% are predicting “negative” prospects.

Discussion in the contract services sector also revolves around the shortage of available contract capacity for glucagon-like peptide 1 (GLP-1) drugs. The impact of the BIOSECURE Act and how it may affect contract service industry prospects is also a major concern. According to the report, a consensus among survey respondents suggest that the Act has further accelerated the post-COVID trend for greater supply chain diversity; both US-based and particularly India-based CDMOs are reporting greater interest in establishing strategic partnerships.

A significant finding in the report is that a majority of the industry does not support the BIOSECURE Act’s stated goals. Nineteen percent view China based-CDMOs as “a threat and should be removed from Western supply chains”, whereas 38% of respondents argue that BIOSECURE is a “politically motivated issue that sets a concerning precedent for the industry.” The remaining 43% of industry respondents, in other words, the largest grouping, have a balanced view, where they both support “WuXi’s tremendous contribution to the industry,” but at the same time want to err on the side of caution, believing it is sensible for the industry to “diversify supply partners.”

“The contract services zone at CPHI continues to grow year on year, in large part driven by the industry’s need for trusted partners who can provide capacity, help navigate the nuances of complex therapeutics and support the road to commercialization. CPHI Milan serves as a vital platform for connecting existing and prospective partners, and we look forward to continuing to serve this growing industry segment in 2025, and beyond. We also see a desire among our attendees [i.e., the people awarding contracts] to meet current partners and advance projects, but also to significantly widen their networks as we head into 2025,” said Tara Dougal, Brand & Content director at CPHI Milan, in the press release.

The research findings show that global innovator and generic-drug pharma companies are actively looking for wider supply chain customers and key development partners. With more than 600 contract services providers expected to attend CPHI Milan on Oct. 8–10, partnering discussions are expected to increase as biotech funding motivates greater deal volumes for 2025 and beyond.

CPHI Milan will host 150 speakers and hold more than 100 sessions across multiple facets of pharmaceutical discovery, development, manufacturing, and production. Approximately 62,000 professionals in the pharmaceutical industry are expected to attend.

According to the survey results, 49% of industry respondents are “highly positive” on the contract services sector seeing growth over the next 18 months.

Results from CPHI Milan Survey Find No Favor Among Industry for BIOSECURE Act While Predicting Faster Growth for CDMOs in 2025

Biopharmaceutical manufacturing largely involves biomolecules whose stability depends on temperature. Antibodies, insulin, and, more recently, messenger RNA (mRNA)-based vaccines are examples of biotherapeutics that require cold storage. This article explores the difficulties with developing stability-enhancing formulations for temperature-sensitive biomolecules and technology innovations that are enabling their formulation. 

Prioritizing Formulation Strategies for Temperature-Sensitive Biotherapeutics

Factors that have been most challenging in developing formulations that enhance stability in temperature-sensitive biomolecules include buffer, pH, and sugar. These are usually the typical factors that need to be evaluated to thermodynamically stabilize monoclonal antibodies (mAbs), notes Joseph Cao, PhD, senior scientist, Analytical and Formulations Development, Bionova Scientific. He explains that there are different types of buffers, sugars, and a range of pH to choose from when developing a proper formulation for mAbs that will prevent aggregation, degradation (such as deamidation, oxidation), and particle formation. Besides those factors, amino acids, salts for ionic strength, and excipients are also important in developing a formulation recipe, he adds.

In addition, the limited amount of therapeutic protein to work with poses another challenge to formulation development. “With design of experiment (DoE), it has allowed us to cut the amount of protein and help us efficiently screen for factors,” Cao says. “Freeze-thaw cycles, container combability, and manufacturing impurities should also be considered during formulation development.”

Heonchang Lim, director, Formulation Development, Samsung Biologics, agrees that finding the ideal range of pH and buffer conditions while selecting the optimal formulation condition to get a good thermal stability property are primary factors that challenge formulation development in these molecules. However, he notes, the thermal stability problem can mostly be solved by using optimal pH buffer and excipient combination.

“Nowadays, we bump into another challenge to develop an optimal formulation condition. That is regarding solubility and hydrophobicity of the molecule. Though clients would prefer higher concentrations, when taking unique characteristics of molecules into consideration, formulation scientists cannot always get high enough concentrations. In addition, pH shift may occur due to the Donnan effect,” Lim says. “Consequently, when a client requests a highly concentrated formulation, particularly above 100 mg/mL, [the] formulation team at Samsung Biologics implements rigorous gate checks to prevent such challenges from arising during formulation stages.”

Meanwhile, Caroline Ailhas, Pharmaceutical Development director, CARBOGEN AMCIS says that, for her, the main factors challenging formulation development for temperature-sensitive molecules revolve around maintaining the structure and functionality of the molecule and defining the required duration of stabilization. The latter can vary from a few days—to allow for manufacturing and visual inspection before storage at 2–8 °C—to several months, or even years. “The definition of this duration significantly impacts the formulation strategy,” Ailhas says.

“One of the key performance indicators for the development of biotherapeutic formulations is colloidal stability to prevent protein aggregation and potentially precipitation,” Greg Chrimes, site head and vice-president, Analytical and Formulation Science, KBI Biopharma, adds. He points out that proteins may denature and aggregate at interfaces such as air/liquid, liquid/liquid, and liquid/solid. Chemical modifications and degradation may also impact effector function, efficacy, conformational stability, and other important parameters, he emphasizes.

Pharmaceutical Technology’s Trends in Formulation

When referring to this article, please cite it as Mirasol, F. Prioritizing Formulation Strategies for Temperature-Sensitive Biotherapeutics. 

Solving the challenge of better-stabilized temperature-sensitive biomolecules hinges on innovative formulation strategies.

The biopharmaceutical industry has long been working on methods to delivery biologic therapeutics in a manner that will enhance ease-of-use and patient compliance. Biologics today are largely administered parenterally, a method that can be painful and undesirable for patients. Furthermore, parenteral formulations of biologics require a strict temperature-controlled environment. Researchers have long been exploring means to formulate biologic-based molecules that can ensure their molecular stability and mitigate some of the stringent manufacturing requirements. In this episode of the Drug Solutions podcast, Feliza Mirasol, science editor of 

® explores the issues challenging biologic formulation and the progress made so far in moving toward alternative routes of biologic drug delivery with Nigel Theobald, CEO of N4 Pharma, a specialist pharmaceutical company developing novel delivery systems for oncology, gene therapy and vaccines.

Nigel Theobald is CEO of N4 Pharma, a specialist pharmaceutical company developing novel delivery systems for oncology, gene therapy and vaccines. Theobald has over 25 years’ experience in healthcare, in building businesses, strategy development and implementation, and in a strong network covering all aspects of pharmaceutical product development and commercialization. He was the head of healthcare brands at Boots Group plc in 2002 before leaving to set up a series of successful businesses, including Oxford Pharmascience Group plc, which he grew over five years into an AIM-quoted company with a market capitalization of £40 million (US$53 million) upon departure. Theobald formed N4 Pharma in 2014.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this podcast episode, we discuss both the challenges of and the progress made so far by the biopharma industry toward non-parenteral means of delivering biologic drugs.

Drug Solutions Podcast: Alternative Drug Delivery Methods for Biologics: Where Are We At?

Lonza announced on Sept. 24, 2024 that it has entered into a long-term commercial supply agreement with Vertex Pharmaceuticals under which it will manufacture Casgevy (exagamglogene autotemcel), the first clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9)-gene-edited cell therapy for treating sickle cell disease (SCD) and β thalassemia.

Under the agreement, Vertex will have access to Lonza’s scientific, regulatory, and manufacturing expertise as well as its global manufacturing network and its experience in the commercial manufacture of cell therapy products. Lonza plans to manufacture Casgevy at its cell therapy manufacturing facilities in Geleen, the Netherlands, with plans to expand to its Portsmouth, NH manufacturing facility in the United States.

“It is a privilege to work with Vertex on bringing its innovative and cutting-edge medicines to patients suffering from life-threatening diseases. We are also pleased to reach a significant milestone towards supporting the commercial manufacture of Casgevy by receiving the regulatory approval at our state-of-the-art cell therapy manufacturing site in Geleen,” said Daniel Palmacci, president, Cell & Gene, Lonza, in a company press release.

The Geleen facility recently received a good manufacturing practice (GMP) license from FDA, the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Lonza expects the Portsmouth site to begin GMP operations in 2025.

“Manufacturing a first-of-its-kind therapy [such as] Casgevy is complex and requires advanced technology and capabilities. The Lonza team have been excellent partners as we have invested in our global manufacturing network to ensure Casgevy will be available for the patients who need it. We look forward to our continued collaboration,” said Morrey Atkinson, PhD, executive vice-president and chief technical operations officer, head of Biopharmaceutical Sciences and Manufacturing Operations, Vertex, in the press release.

Casgevy was approved by the MHRA in November 2023 (1), by FDA in December 2023 (2), and by EMA in February 2024 (3). Following the MHRA and FDA approvals in late 2023, Vertex 

, a UK-based cell and gene therapy contract development and manufacturing organization, in December 2023 (4) to manufacture Casgevy. RoslinCT runs manufacturing facilities in Edinburgh, Scotland, and Boston, Mass., which are purpose-built for cell therapy products. The CDMO had been working with Vertex on an adaptive basis while Vertex moved through clinical and regulatory development of Casgevy.

1. Vertex Pharmaceuticals. Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia. Press Release, Nov. 16, 2023.
2. FDA. 

FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease

. Press Release, Dec. 8, 2023.
3. Vertex Pharmaceuticals. European Commission Approves First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia. Press Release. Feb. 13, 2024.
4. RoslinCT. RoslinCT to Manufacture First-Ever US FDA Approved CRISPR-Based Gene Therapy Casgevy (exagamglogene autotemcel). Press Release. Dec. 11, 2023.

Lonza signed a long-term supply agreement to manufacture CASGEVY (exagamglogene autotemcel) for Vertex at its facility in Geleen, the Netherlands, and plans to expand manufacturing to Portsmouth, NH, in the United States.