Nicholas Saraceno is editor at Pharmaceutical Commerce.

Nicholas Saraceno

Kedrion Biopharma, a US-based biopharmaceutical company specializing in plasma-derived therapeutics, announced on Nov. 19, 2024 that FDA has approved its manufacturing facility in Bolognana, Italy, to produce Ryplazim (plasminogen, human-tvmh), a plasma-derived human plasminogen indicated for treating patients with plasminogen deficiency type 1 (PLGD-1), or hypoplasminogenemia (1).

PLGD-1 is a rare chronic disease that mainly appears in the form of “abnormal extra-vascular fibrin-rich, ligneous” lesions on various mucosal surfaces throughout the body. Most notably, lesions occur in the eye (known as ligneous conjunctivitis); however, their appearance in the respiratory, gastrointestinal, and genitourinary tracts—along with the central nervous system, ears, mouth, and skin—is not uncommon. They can potentially lead to serious consequences, including obstruction of airways; infertility; and hydrocephalus, along with vision and hearing loss.

"The FDA's approval of our Bolognana facility is a pivotal moment for our company, and I want to thank all employees worldwide who contributed to this achievement," said Bob Rossilli, chief commercial officer, global business and US general manager, Kedrion Biopharma, in a company press release. "This expanded capacity for Ryplazim means we can provide treatment for more patients with PLGD-1. Offering a product like [Ryplazim] to patients in need is truly a privilege."

This development signifies greater patient access to this PLGD-1 medication, not only in the United States, but globally as well. Ryplazim is considered the first and only FDA-approved therapy specifically for the PLGD-1 indication after receiving approval in June 2021; Kedrion officially announced plans to commercialize and distribute the product later that year (2). The active ingredient in Ryplazim is plasminogen, which is purified from human plasma (3). Treatment with Ryplazim helps to increase the plasma level of plasminogen, helping to limit or remove the lesions.

In a single-arm, open-label (unblinded) clinical trial that enrolled 15 adult and pediatric patients with PLGD-1, patients were administered Ryplazim every two to four days for 48 weeks. Overall, the medication’s effectiveness was apparent by at least a 50% improvement of their lesions in all 11 patients who had lesions at baseline, while there were no new lesions in any of the 15 patients through these 48 weeks (3). The most common side effects that patients reported were abdominal pain, back pain, bloating, bleeding, constipation, dry mouth, dizziness, fatigue, limb pain, nausea, headache, and joint pain (3).

"With increased awareness of PLGD-1, the expanded capacity of Ryplazim ensures we are better equipped to meet the growing demand, noted Rebecca Bialas, MD, co-founder and chair of The Plasminogen Deficiency Foundation, in the release (1). “This means more patients who receive the correct diagnosis can be confident they will get the treatment they so desperately deserve and need. This is an exciting time for the PLGD-1 community, marking a significant event in our collective journey towards better health."

1. Kedrion Biopharma. FDA Approves Kedrion's Bolognana Facility for Production of First and Only Treatment for PLGD-1, Ryplazim. Press Release. Nov. 19, 2024.
2. Kedrion Biopharma. Kedrion Biopharma to Commercialize Ryplazim in US. Press Release. Oct. 20, 2021.
3. FDA. FDA Approves First Treatment for Patients with Plasminogen Deficiency, a Rare Genetic Disorder. Press Release. June 4, 2021.

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FDA's approval will allow Kedrion to manufacture Ryplazim (plasminogen, human-tvmh), the only FDA-approved therapy for treating PLGD-1, at facility in Bolognana, Italy.

FDA Grants Approval to Kedrion to Produce PLGD-1 Therapeutic at Bolognana Plant

On Nov. 20, 2024, Fujifilm Diosynth Biotechnologies announced the completion of an expansion at its Thousand Oaks, Calif., cell therapy manufacturing facility (1). At a celebration for the opening of the updated facility, the company also recognized the issuance of a Certificate of GMP Compliance of a Manufacturer for the site, granted to it by the European Medicines Agency (EMA).

The investment project was originally announced (2) in December 2023 as one component of the company's $200 million cell therapy development and manufacturing investment project; the plan also involves financially supporting its Fujifilm Diosynth Biotechnologies’ California site, Fujifilm Cellular Dynamics, Inc.’s new headquarters (HQ) in Madison, Wis., and the Cellular Dynamics' new HQ with cell therapy manufacturing services, which is expected to be up and running by 2026.

When it comes to the Thousand Oaks location, the development project features the advancement of the development labs and welcomes two new independent cell therapy production suites to the mix, which boosts cleanroom capacity. The current good manufacturing practice (CGMP) suites are capable of automated cell separation and selection, with expansion equipment, in-built decontamination for rapid changeovers, and heating, ventilation, and air conditioning systems that can support either Grade B or C backgrounds.

Further, these suites can handle either open or closed processing—they’re also large enough to accommodate multiple patients’ autologous program lots, or even greater volume batches for allogeneic programs for both the clinical and commercial marketplaces.

“The completion of the expansion at our California cell therapy facility demonstrates our ability to support the growing needs of our early-to-late-stage allogeneic customers and late-phase autologous customers for commercial cell therapies," said Lars Petersen, president and CEO, Fujifilm Diosynth Biotechnologies, in a company press release (1). “As our industry realizes the promise of precision medicine, we are pleased to be at the ready to support production at our California facility, with the specialized skill and expertise of our team on-site.”

As alluded to previously, the California plant recently was given EMA regulatory approval, specifically for the manufacturing of sterile, biological medicinal products, and quality control testing specifically for Atara Biotherapeutics’ Ebvallo (tabelecleucel or tab-cel), which is a monotherapy that was approved in Europe for adults and children with relapsed or refractory Epstein‑Barr virus positive post‑transplant lymphoproliferative disease (r/r EBV+ PTLD).

Overall, in 2023, the global cell therapy market size was estimated to be valued at $4.8 billion, and forecasts are anticipating that the market will continue to grow at a compound annual growth rate of 37% during 2023 to 2030 forecast period (3).

“I am very proud of our entire team for reaching these important milestones, which will benefit patients that rely on these important cell therapies,” commented Dave Bolish, site head of Fujifilm Diosynth Biotechnologies, California, in the release (1). “The recent EMA GMP certification exemplifies that our high-quality manufacturing processes, systems, talent, and world-class facility meet regulatory requirements, and we have the agency’s trust to manufacture and deliver product on behalf of our partner.”

1. Fujifilm Diosynth Biotechnologies Celebrates the Expansion Completion at its California Cell Therapy Facility. Press Release. Nov. 20, 2024.
2. Fujifilm to Invest USD 200 Million to Expand Cell Therapy Development and Manufacturing Capabilities. Press Release. Dec. 4, 2023.
3. Fujifilm estimates based on Evaluate Pharma November 2023.

The Thousand Oaks, Calif., cell therapy manufacturing facility now houses new production suites, updated development labs, and more after expansion.

Fujifilm's Cell Therapy Facility Expansion Completed

On Nov. 19, 2024, Pharmaceutics International, Inc. (Pii), a contract development and manufacturing organization (CDMO), announced that it is investing $3.6 million into its prefilled syringe (PFS) services, specifically to boost its advanced labeling, automated visual inspection, and fill/finish technology (1). The investment will allow the CDMO to provide end-to-end, streamlined solutions for drug manufacturing.

Pii’s decision was partially influenced by the demand for prefilled syringe solutions in the pharmaceutical and biotech sectors. The aforementioned investment will go towards a syringe labeler, along with an Antares automated visual inspection (AVI) system.

“With this expansion, Pii strengthens its role as a comprehensive partner, allowing clients to achieve faster time-to-market by managing every step of the PFS process,” said John Fowler, Pii’s CEO, in a press release. “Our streamlined approach will support customers in optimizing both cost and quality, meeting stringent regulatory demands, and ultimately improving patient access to essential therapies.”

The branded syringe labeler is in the process of being installed, and is expected to be fully operational by either the first half or early second half of 2025. Essentially, it automates syringe labeling, plunger insertion, and safety device integration.

The concept of combining advanced labeling, automated visual inspection, and fill/finish tech services limits logistical and regulatory complexities when it comes to product delivery timelines. It also helps with quality control, which reduces the risk of errors.

As for the Antares AVI technology, the anticipated operational date is the third quarter of 2025. The system is able to detect air bubbles, cracks, particles, and fill-level discrepancies. It also reportedly decreases dependence on manual inspections, while boosting large-scale production turnaround times, and supporting regulatory requirements that surround quality analysis and traceability.

In other Pii news, over the past year, the company had announced a new leadership team (2) consisting of Joseph Kiely as chief financial officer; George Sanders as vice-president (VP) of human resources, Thomas Pamukcoglu as VP of quality; James Drob as head of aseptic manufacturing; John Phillips as VP of sales; Bob Talley as general counsel and assistant secretary, and Alexander Borodin as senior director of supply chain. Devan Patel was also promoted to VP of client services, while Sara Frederick, joined the team as senior director of business operations.

“I’m delighted to continue this journey of implementing real cultural change within the company. Among their responsibilities will be oversight of new operational processes and systems that will improve our ability to deliver on time and in full,” said Pii CEO John Fowler in a press release issued at the time (2). “Every one of these new team leaders is an incredible addition to our company and an important piece of our company-wide strategy to provide best in class services to our partners.”

1. Pii Expands Prefilled Syringe Services with $3.6M Investment in Capacity and Technology Upgrades. Press Release. Nov. 19, 2024. 
2. Pharmaceutics International Onboards New Leadership Team to Drive Quality, Operational Improvements, and Growth. Press Release. March 20, 2023. 

The $3.6 million investment will allow the CDMO to boost its advanced labeling, automated visual inspection, and fill/finish capabilities.