Susan Haigney

Communication between the manufacturing plant and retail stores. | Image Credit: © Cagkan - © Cagkan - stock.adobe.com

IMA Life North America held a groundbreaking ceremony on May 8, 2024 for its new 80,000-square-foot facility in Tonawanda, NY. The facility is being built to increase production for the company’s freeze-drying equipment.

The Tonawanda facility is planned to open in September 2024 and will feature 50,000 square feet of production space and 30,000 square feet of office space on 15 acres. This new facility will supplement IMA Life’s current 60,000-square-foot facility in Tonawanda. New York State will provide up to $1,127,443 in performance-based Excelsior Jobs Program tax credits through the NY’s economic development agency, Empire State Development (ESD), in return for IMA’s commitment to job creation with an additional 70 employees. ESD promotes the creation of new job through the use of loans, grants, tax credits, and other financial assistance to enhance private business growth in New York State.

“New York is continuing to bring the companies, the investment, and the talent to build the future of medicine in our state. IMA Life’s investment in Western New York will help provide the critical equipment needed for pharmaceutical companies to manufacture life-saving drugs, while also creating the jobs needed to grow and support the healthcare sector,” said New York Governor Kathy Hochul during the groundbreaking ceremony (1).

Ernesto Renzi, president of IMA Life North America, said, 

We have deep respect for the life-saving medicines our customer’s process using IMA equipment, and we look forward to expanding our production capabilities and adding jobs right here in Western New York. The impressive competence of the workforce has allowed us to grow our customer base and expand the company.”

IMA Life North America is one of six IMA Life production sites. IMA Life produces equipment that meets maximum levels of sterility and is shipped worldwide. The Tonawanda facility manufacture large freeze dryers that rapidly convert vials of liquid medicines into a shelf-stable powdered form that is easy to transport. Products include blowers, washers, depyrogenating tunnels, liquid and powder fillers, freeze dryers, automatic loaders/unloaders, labelers, and isolation systems.

At INTERPHEX 2024 in New York City in April, IMA Life received the Best New Product/Service award for the company’s KryoAir air-based refrigeration system for freeze dryers. KryoAir is a single-state, oil-free system that requires minimal maintenance and can deliver consistent cooling output across different temperatures, according to the company (2).

The turbo-compressor-expander technology is augmented by the Cold Thermal Energy Storage (CTES) system, which harnesses the power of phase-transitioning compounds to maximize capacity per unit of volume. This enables the turbo-compressor-expander technology to support intensive and discontinuous energy applications.

“Pairing CTES with the turbo compressor expander, KryoAir transforms a well-established technology into a powerhouse of clean energy utilization. This dynamic synergy allows KryoAir to achieve extreme low temperatures with unprecedented efficiency, all while maintaining a compact and reliable design,” the company stated in a press release (2).

IMA Life. Groundbreaking Ceremony for IMA Life North America in Tonawanda, USA. Press Release. May 16, 2024.

IMA Life. IMA Life Wins INTERPHEX NY Awards for the Third Consecutive Year. Press Release. April 10, 2024.

Articles

The new 80,000-square-foot facility will increase production of the company’s freeze-drying equipment.

IMA Life North America Breaks Ground on New Facility in Tonawanda, NY

Science laboratory test tubes, laboratory equipment | Image Credit: © BillionPhotos.com - © BillionPhotos.com - stock.adobe.com

Regeneron presented results from an ongoing Phase I/II clinical trial for its investigational gene therapy, DB-OTO, at the annual American Society of Gene and Cell Therapy (ASGCT) meeting, being held in Baltimore, Md. from May 7–11. DB-OTO, a gene therapy for genetic deafness, improved hearing in one child, treated at 11 months old to normal levels within 24 weeks. A second child, treated at 4 years old, also showed hearing improvements at a six-week assessment, according to the company (1). Both children were born with genetic deafness due to variants of the otoferlin gene.

The results are from the ongoing Phase I/II CHORD (

) first-in-human, multicenter, open-label trial. The trial evaluates the safety, tolerability, and preliminary efficacy of DB-OTO in infants, children, and adolescents with otoferlin (OTOF) variants in the United States, United Kingdom, and Spain. CHORD is a two-part study where participants will receive a single intracochlear injection of DB-OTO in one ear in Part A of the study. In Part B, participants receive simultaneous single intracochlear injections of DB-OTO in both ears at the selected dose from Part A.

Congenital deafness impacts approximately 1.7 out of every 1000 children born in the United States, according to Regeneron (1). Otoferlin-related hearing loss is especially rare and caused by variants in the otoferlin gene, “which impairs the production of the OTOF protein that is critical for the communication between the sensory cells of the inner ear and the auditory nerve.”

Study data presented at ASGCT showsat the 24-week assessment the first participant, a 16-month-old child, had “improvement of hearing to normal levels across key speech frequencies, with an average 84 dB improvement from baseline and one frequency measure reaching 10 dB in hearing level per PTA. Across all tested frequencies, an average 80 dB improvement from baseline was observed.” There was also positive ABR responses, with best frequency reaching 45 dB.

The second participant, a four-year-old child, experienced consistent results to the first participant, including “initial improvement of hearing with responses to loud sounds, which was observed across key speech frequencies, with an average 19 dB improvement from baseline and one frequency measure reaching 80 dB in hearing level per PTA. Across all tested frequencies, an average 16 dB improvement from baseline was observed.” Positive ABR responses had best frequency reaching 75 dB.

“The opportunity of providing the full complexity and spectrum of sound in children born with profound genetic deafness is a phenomenon I did not expect to see in my lifetime,” said Lawrence R. Lustig, MD, chair of Columbia University’s Department of Otolaryngology–Head & Neck Surgery and a clinical trial investigator, in a press release. “These impressive results showcase the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related deafness, and we are excited to see how this translates into an individual’s development, especially [because] early intervention is associated with better outcomes for speech development. With the DB-OTO CHORD trial now enrolling participants in sites across the US and Europe, we’re part of the beginning of a new era of gene therapy research that looks to create treatment options that address the root cause of profound genetic deafness.”

1. Regeneron. Latest DB-OTO Results Show Dramatically Improved Hearing to Normal Levels in a Child with Profound Genetic Deafness Within 24 Weeks and Initial Hearing Improvements in a Second Child at 6 Weeks. 

The company’s presentation at ASGCT includes preliminary data results for a child who received the gene therapy.

Regeneron Presents Update on Gene Therapy for Genetic Deafness at ASGCT

Capsida Biotherapeutics presented new preclinical evidence for its first-in-class IV administered gene therapy, CAP-002, on May 7, 2024 at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in Baltimore. The presented data support the potential of CAP-002 to achieve levels of gene supplementation that corrects neurological phenotypes associated with genetic epilepsy due to syntaxin-binding protein 1 (STXBP1) mutations. CAP-002 is a “first-in-class next-generation intravenous (IV)-administered gene therapy that achieves brain-wide neuronal expression while simultaneously detargeting the liver” (1). The program is in investigational new drug-enabling studies and the company expects the therapy to enter the clinic in the first half of 2025.

Mutations in the syntaxin-binding protein 1 (STXBP1) gene cause genetic epilepsy, which impacts an estimated one in 30,000 children born each year globally. Severe developmental delay and intellectual disability, treatment-resistant seizures, and sudden unexpected death in epilepsy (SUDEP). The STXBP1 protein is present in every neuron in the brain and is essential for normal neurotransmission. There are no disease-modifying therapies for this disorder.

According to the company, earlier-generation adeno-associated viruses (AAVs) or wild-type AAVs could not achieve the level of widespread neuronal transduction that would be needed to modify the disease. Gene therapy for genetic epilepsy due to STXBP1 mutations, therefore, has not been previously possible.

The first presentation at the ASGCT event, “AAV Gene Therapy Corrects Neurological Phenotypes with Clinically Relevant Doses in a Mouse Model of STXBP1-Related Developmental and Epileptic Encephalopathy,” is co-authored with Mingshan Xue, PhD, associate professor, Department of Neuroscience, Department of Molecular and Human Genetics at Baylor College of Medicine and the Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.

The study showed that “IV administration of the gene encoding STXBP1 in adult mice lacking one functional copy of the STXBP1 gene rescues key phenotypic defects in a dose-dependent manner and does so with long-lasting effects” (1). The dose-dependent rescue of neurological phenotypes (i.e., epileptic seizures, motor deficits, and cognitive impairments) was observed to be dependent on “supplementation of STXBP1 in neurons throughout the brain and at levels not achievable by wild-type serotypes, such as AAV9.”

“This study built upon our previous proof-of-concept study and represents a significant advancement in our understanding of the therapeutic potential of engineered AAV gene supplementation therapy in the treatment of genetic epilepsy and developmental disorders due to STXBP1 mutations. These data are encouraging and emphasize the potential for CAP-002 to meaningfully improve outcomes in patients with this disease,” said Xue.

On May 8, 2024, Capsida will present additional data in a poster presentation that show “a single IV infusion of CAP-002 results in brain-wide STXBP1 gene expression and is capable of transducing up to 70% of neurons at therapeutically relevant doses in non-human primates (NHPs). This level of gene expression raises neuronal STXBP1 protein to levels comparable to those that reversed disease phenotype in the mouse model. CAP-002 had no clinical pathology, histopathology, or immunogenicity findings” (1).

“These data demonstrate that our STXBP1 program effectively crosses the blood-brain barrier in NHPs following IV delivery and achieves breakthrough levels of widespread brain transduction and STXBP1 protein expression needed to achieve disease-modifying impact as demonstrated in the mouse model data,” said Capsida’s Chief Scientific Officer, Susan Catalano, PhD. “Coupled with significant detargeting of the liver compared to AAV9, CAP-002 holds the promise of effectively reversing disease and does so via less-invasive IV administration. We look forward to advancing our STXBP1 program into clinical development in the first half of 2025, so that we can bring this disease-modifying treatment option to people suffering from this devastating disease.”

1. Capsida. Capsida Biotherapeutics Presents New Preclinical Evidence Indicating Novel First-in-Class IV-Administered Gene Therapy Effectively Treats Genetic Epilepsy Due to STXBP1 Mutations. Press Release. May 7, 2024.



The company is presenting preclinical data at the American Society of Gene & Cell Therapy annual meeting that supports the potential of the company’s CAP-002 gene therapy for correcting neurological phenotypes associated with genetic epilepsy due to syntaxin-binding protein 1 (STXBP1) mutations.

Data for First-in-Class IV-Administered Gene Therapy to Treat Epilepsy Presented at ASGCT 2024

On April 17, 2024, CordenPharma, a contract development and manufacturing organization (CDMO) that manufactures APIs and injectable products, provided an update on the company’s partnership with GENEPEP, a contract research organization (CRO) that designs, synthesizes, and optimizes peptides, peptide libraries, and proteins. The CDMO and CRO created their partnership in 2023 to support biotech companies with the development and manufacturing of peptides for early clinical phases.

To assist their clients, the CDMO and CRO have combined CordenPharma’s current good manufacturing practice (CGMP) capacities and regulatory experience with GENEPEP’s discovery and drug development knowledge. GENEPEP provides research and discovery services and support for initial investigational new drug (IND) applications, which includes selection of lead and alternative compounds, research grade samples, and gram peptide manufacturing samples. CordenPharma then provides early clinical GMP manufacturing at its Frankfurt site, as well as access to the company’s global sales and marketing organization.

“With our new early clinical GMP peptide manufacturing investment in Frankfurt and the strategic partnership with GENEPEP, we are proud to strengthen our peptide offering for biotech and pharma customers in early discovery to first-in-human clinical stage,” said Stéphane Varray, CordenPharma’s Global Peptide Platform director, in a press release (1). “In the past 12 months, we have demonstrated together how this collaboration has simplified and expedited the critical milestones of lead development and validation in a clinical setting, bringing added value for our global customers.”

“Thanks to this collaboration between GENEPEP [and] CordenPharma, customers of both companies now have access to collaborative and specialized teams tailored to meet the needs of each of the research and development phases of their project,” added Karine Puget, founder and CEO of GENEPEP.

CordenPharma also announced on April 17 the launch of a lipid nanoparticle (LNP) β-sitosterol process that supports sustainable emission reduction targets (2). In December 2022, CordenPharma joined the Science Based Targets initiative (SBTi) and evaluated and developed science-based targets for reducing greenhouse gas emissions. In February 2024, the company introduced β-sitosterol, which enhances endosome escape ability and advances messenger RNA transfection efficacy.

“Because of our commitment to SBTi targets, during the process design of β-sitosterol we prioritized the identification of a reliable and sustainable source of starting material for its production, thereby reducing the high CO

 [carbon dioxide] emissions impact normally in place with traditional chemical steps requiring solvents and chemical consumption. Working closely with members of the American Forest & Paper Association, known for their leadership in sustainable forest management practices, CordenPharma committed to the responsible sourcing of an innovative plant-based β-sitosterol starting material derived from softwoods used in the kraft paper making process, and in the process ensured that every harvested tree is replaced by three new trees,” the company stated in a press release (2). “The β-sitosterol production process concludes with a sophisticated purification technology, enabling the recycling of over 98% of the main eluent directly into the same process, further enhancing sustainability and resource efficiency. These actions reinforce CordenPharma’s green initiatives and further our overall goal to create efficient SBTi reduction targets.”

“Joining the Science Based Targets initiative underscores our unwavering commitment to sustainability in order to combat climate change,” Matthieu Giraud, CordenPharma’s senior director, Global Lipids & Carbohydrates Platform, said in the release. “We recognize the urgent need for action, and through this initiative, we are taking concrete steps—as exemplified in our implementation of sustainable β-sitosterol production—to reduce our environmental footprint not only in our facilities, but across our platforms using innovative technologies that contribute to a healthier planet.”

1. CordenPharma. CordenPharma & GENEPEP Celebrate Strong Collaboration Leveraging Peptide Drug Substance Discovery & Clinical Development Expertise. Press Release. April 17, 2024. 

https://cordenpharma.com/articles/press-release-cordenpharma-genepep-leverage-peptide-drug-substance-discovery-and-clinical-expertise/

2. CordenPharma. Launch of Innovative LNP β-sitosterol Process Supports Sustainable Emission Reduction Targets. Press Release. April 17, 2024. 

https://cordenpharma.com/articles/innovative-beta-sitosterol-process-supports-sustainable-emission-reduction-targets/

CordenPharma’s partnership with GENEPEP expedites lead development and validation in project phases, and its LNP β-sitosterol supports sustainable emission reduction targets.

CordenPharma Leverages Peptide Drug Discovery and Development with GENEPEP and Works on Reducing Emissions

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Cytiva unveiled the Xcellerex single-use magnetic mixer at INTERPHEX 2024 in New York City on April 16, 2024. The single-use mixing system was designed to combat challenges in large-scale monoclonal antibody (mAb), vaccine, and genomic medicine manufacturing processes. The mixer is offered in 2000 L and 3000 L capacities and can be configured in several ways to accommodate diverse mixing processes. Its compact size benefits facilities with space constraints or complicated installation of large-scale consumables.

According to the company, minor leaks may cause significant delays and losses. “When dealing with a 3000 L batch of cell culture media, the estimated financial loss can cost between $60k to upwards of $100k” (1). The system helps prevent expensive leaks with a novel mixer biocontainer that incorporates user-centered design elements to improve durability and ease of use. The design provides enhanced safeguards and added protection from leaks that may occur during shipping, storage, and operation.

Time taken to mix batches can inhibit product development times, specifically the challenge of mixing floating powders such as cell culture media. Current systems have underpowered impellers with circular or cubical shapes that make producing large volumes challenging, according to Cytiva. This new single-use system “has a powerful impeller that when combined with the mixer’s hexagonal shape creates a vortex, enhancing the interaction at the liquid surface. This vortex effectively pulls down the floating powders into the main body of the liquid to allow for a more efficient and shorter mixing process,” the company stated in a press release.

“We're tapping into our differentiated portfolio to solve a wide range of challenges for our customers. Our new magnetic mixing system is flexible and capable of meeting the many demands and constraints during buffer and cell culture media preparation,” said Amanda Halford, president, Bioprocess at Cytiva in the release. “By reimagining the design, we’ve tackled some of the biggest obstacles to downtime.”

Cytiva is also working to advance messenger RNA (mRNA) manufacturing. In an interview with 

Scott Ripley, general manager, Nucleic Acid Therapeutics and Precision Nanosystems at Cytiva, 

discussed technology that enables the “democratization” of mRNA manufacturing

 (2). Many mRNA therapies and other types of genetic medicines in clinical development are designed to be delivered with the help of lipid nanoparticles. One such platform is Cytiva’s Precision Nanosystems NanoAssemblr microfluidic-based nanoparticle manufacturing platform, which enables the development of genetic medicines with potentially increased stability, efficacy, yield, and quality of non-viral genetic medicines, according to Ripley.

Ripley was enthusiastic about this platform’s ability to “democratize” the good manufacturing practice (GMP) manufacturing aspects for advanced therapies, while managing to cope with the increased molecular diversity of the molecules being handled.

“For example,” Ripley says, “the mRNA platform is unique in that, on one end of the spectrum, it is vaccinating the planet, on the other end, it’s personalized cancer vaccines.”

Cytiva Unveils Latest Innovation for Large Scale Mab, Vaccine, and Advanced Therapy Manufacturing Processes–The Xcellerex Compact Single-Use Magnetic Mixing System

. Press Release. April 16, 2024.
2. Spivey, C. 

Democratizing GMP Manufacturing for the New Therapeutic Pipeline

The Xcellerex magnetic mixer, single-use mixing system was designed to address challenges in large-scale mAb, vaccine, and genomic medicine manufacturing processes. 

Cytiva Showcases Single-Use Mixing System at INTERPHEX 2024

AES Clean Technology announced the launch of its CleanLock Module at INTERPHEX 2024 on April 16, 2024. The airlock solution for cleanrooms is engineered to minimize the risk of contamination by integrating AES’ proprietary cleanroom finishes, patented lighting, predictable airflow patterns, and advanced door controls. These features can be integrated into any facility without delay. The CleanLock Module allows for secure transition of people and materials entering and existing cleanrooms. AES, a modular cleanroom facilities provider, is inviting attendees of INTERPHEX 2024 to visit their booth, 2509, to learn more about the CleanLock Module.

"We are thrilled to introduce the CleanLock Module airlock to the market," said Grant Merrill, AES chief commercial officer, in a press release (1). "This product addresses the critical need for maintaining ultra-clean environments in industries such as pharmaceuticals, biotechnology, and medical device manufacturing. With its state-of-the-art technology and precision engineering, the CleanLock Module will set a new standard for contamination control and efficiency in design and construction execution."

The CleanLock Module joins the company’s series of cleanroom products. Its three-dimensional design modularizes coordinated and repeatable segments of any cleanroom project “to accelerate installation, maximize quality, improve site safety, and deliver predictable performance” in one single packaged solution.

Cleanrooms are an integral part of contamination control in pharmaceutical manufacturing. Flexibility in constructing cleanrooms should consider the process application they are used for (2). “This [flexibility] is especially important for multi-modal or multi-product processing streams and new therapies, which may not have a clearly defined process design or require process modifications along the way … To truly determine flexibility, one needs to dissect the different flexibility needs and the available solutions. Only then can an appropriate decision be made, which will not just satisfy the short-term requirements, but also show long-term benefits” (2).

In other AES Clean Technology news, in February 2024 the company appointed Chris Barbieri as vice president of Engineering to oversee product development, innovation, and technical advancement initiatives.

“It is an exciting time to welcome Chris to our leadership team. He has a wealth of experience in the industry and will support our mission as the leader in modular cleanroom technology. Bringing passion, energy, and tenacity to his new role, Chris is well positioned to make a real impact on our people, projects, and clients, and our overall future success,” said Shawn Reniker, AES Clean Technology’s senior vice president of Operations, in a press release (3).

“AES has been an established and recognized name within the cleanroom industry for almost 40 years. The team’s capabilities from a design-build and manufacturing standpoint, coupled with its focus and commitment to continuous improvement, innovation, and growth, align perfectly with my professional goals. My extensive background in engineering and project delivery will allow me to provide valuable insights and feedback as AES continues to grow the design and engineering teams. I look forward to elevating AES’ profile as a technical leader and innovator,” Barbieri said in the release.

AES Clean Technology. AES Clean Technology sets new standards for cleanliness and efficiency in cleanrooms with the launch of its CleanLock Module. Press Release. April 16, 2024.

Jornitz, M.W.; Backstrom, S.; Williams, B.; and Powers, D. The Quest for Cleanroom Flexibility. 

Pharmaceutical Technology Trends in Manufacturing

https://www.pharmtech.com/view/the-quest-for-cleanroom-flexibility

AES Clean Technology. AES Clean Technology Appoints New Vice President of Engineering. Press Release. Feb. 20, 2024.

The airlock solution for cleanrooms offers contamination controls for a highly controlled environment.