Feliza Mirasol is the science editor for 

Feliza Mirasol

BioIVT has launched new cleanroom manufacturing space in Winchester, Va. A research partner and biospecimen solutions provider for drug and diagnostic development, the company partnered with Germfree, a provider of modular cleanroom infrastructure and services, to build the space, according to an Aug. 1, 2024 company press release.

The cleanroom comprises design and solutions from Germfree that boost BioIVT’s capabilities in cell and gene therapy (CGT) development. The integration of cleanroom processes will include BioIVT’s good manufacturing practice (GMP)-compliant raw materials for supporting CGTs, including Human AB serum.

“This facility will play a significant role in our expanding portfolio of GMP-compliant products,” said Parijat Jain, vice-president of Cell & Gene Therapy at BioIVT, in a company press release. “The cleanroom was designed in collaboration with Germfree, relying on their extensive expertise to build a facility that will support client-specific manufacturing requirements and configured for high-volume production enabling product use in late-stage clinical and commercial manufacturing. We continue to evolve and strengthen our support for the development of CGT research, and our future-ready cleanroom will provide expanded capabilities and access to developers.”

The new space is purpose built to support workflows for excipient and ancillary material bioprocessing. The cleanroom ensures quality and regulatory compliance and includes the following features:

qualified in accordance with FDA requirements

FDA-current GMP, International Organization for Standardization, ion selective electrode, Center for Disease Control–Biosafety in Microbiological and Biomedical Laboratories, and American Society for Testing and Materials tested

heating, ventilation, and air conditioning controls systems

high efficiency particulate air filtration.

"We at Germfree are honored to contribute to BioIVT's groundbreaking manufacturing space by providing our modular cleanroom technology,” said Kevin Kyle, CEO, Germfree, in the press release. “This new facility reflects BioIVT's dedication to advancing biospecimen solutions and scientific research, and the company’s deep experience in helping manufacturers build cutting-edge facilities. We are excited to support their mission and look forward to the innovative achievements that will benefit the life sciences and pharmaceutical industries, fostering advancements in research and development."

The cleanroom addition is the latest in a series of expansions BioIVT has pushed forward. In February 2024, the company increased its capacity for delivering readily available fresh, standard, and mobilized human leukopaks (1). The additional capacity further builds the company’s ability to scale its network of diverse and highly characterized cell donors. Earlier in October 2023, BioIVT expanded its biospecimen portfolio with the launch of its new Center for NeuroExcellence. Through this center, BioIVT can offer neurology researchers a single source from which they can obtain supplies, from controls to difficult-to-collect biofluid samples from populations with neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (2).

1. BioIVT. BioIVT Announces Expansive Fresh Leukopak Capability in Europe. Press Release, Feb. 22, 2024.
2. BioIVT. BioIVT Expands its Biospecimen Portfolio in Support of Neuroscience Research. Press Release, Oct. 27, 2023.

Articles

BioIVT opened new cleanroom manufacturing space, using Germfree’s technology to boost its capabilities for cell and gene therapy development.

Partners BioIVT and Germfree Open New Cleanroom Manufacturing Space at US Site

Finished pharma product inspection requires stringent oversight that may be lacking in systems that rely on manual or only semi-automated processes. With the rise of automation technologies applied to biomanufacturing systems, having an automated finished product inspection system in place can make up for gaps where a lack of trained personnel may persist.

Finished product inspection starts with an evaluation of the inspection process to determine if it is able to detect defects in a pharmaceutical presentation. Once that determination is made, it is important that the inspection method is established, whether manual, semi-automatic, or fully automated. There are cases where a semi-automated or automated inspection system is not an option, which leaves manual inspection; however, if semi-automated or automated inspection options are available, then an inspection method should be determined based on lot size. In one example, lot sizes under 5000 are likely to utilize manual inspection, while lot sizes between 5000 and 15,000 would likely require a semi-automatic inspection. Above a 15,000-lot size, a fully automated inspection system is the better choice (1).

Mike Pipe, head of Global Sales & Product Management at Mettler-Toledo, points to X-ray technology as one solution in product inspection, noting that there are three main quality control issues that X-ray technology can solve in the packaging area: detection of foreign body contaminants, identifying incomplete or missing medicines, and identifying damaged packaging.

“As any responsible manufacturer knows, there can be no trade-offs in quality standards when it comes to the manufacture of pharmaceutical products. Whether the medicine is in liquid or tablet form, it is essential that foreign body contaminants are detected and removed,” Pipe states. He emphasizes that the dosage or fill levels must be correct, and that the integrity of both the packaging and the product must not have been compromised.

Pipe explains that it is now commonplace for product inspection equipment to be used in the pharma sector to overcome these challenges. “Metal detection systems can be used before tablets are pressed or packed to detect ferrous, non-ferrous, and stainless-steel metal contaminants. Vision systems and checkweighers also play a vital role in ensuring that products are complete, labeled correctly, and are at the correct weight,” he says.

Pipe points out, however, that with tablets being increasingly packaged in aluminum foil-based blister packs, metal detection systems may have a difficult time identifying if metal contaminants are present if the pharma products are inspected after packaging. “This is where X-ray technology can help. [X-ray] can detect a wide range of foreign body contaminants, including metal, both before and during packaging. It can also deliver several further quality assurance benefits,” he states.

Pipe highlights five key areas where X-ray inspection can make an important contribution in pharma production and packaging:

 As pipe points out, foreign body detection is a critical aspect of any pharma manufacturer’s product inspection operation. While metal detection is a robust inspection technology for detecting metal contaminants, including stainless steel, in the preparation or tableting process, X-ray inspection can complete contamination checks early in the production process. Using X-ray can also allow for inspection of contaminants at the final packaging stage following the blister-packing process. X-ray measures differences in absorption between low and high-density matter and can provide exceptional detection not only metal contaminants, but also glass and certain plastics and rubbers, regardless of the contaminant’s shape, size, or location within the product.

Help ensure product and packaging integrity.

 X-ray inspection can carry out a range of additional quality control (QC) tasks while simultaneously detecting foreign body contaminants, including:

Product completeness checks, including counting components and identifying damaged components—with comparison to the known number of items that should be in a pack

Identifying damaged packaging, inspecting seal quality to detect product trapped in the seal, and identifying missing components such as screw caps

Measuring product mass and comparing it to a known mass value for a reference pack

Checking fill levels—X-ray inspection images show clear discrepancies in fill levels between packs, where, for example, one pack may be under-filled and another pack may be over-filled, which can make the overall pack weight seemingly correct.

 Product recalls represent a twin-headed peril for pharma manufacturers, says Pipe. On the one hand, a product recall is costly because of wasted products and production time; on the other hand, a recall causes damage to the pharma manufacturer’s good name. “While the costs of the former are often quickly absorbed, the negative effects on brand reputation can be much more long lasting,” he notes. Therefore, implementing a well-designed X-ray inspection program can cut the risks and the costs involved in product recalls. X-ray “run codes” are assigned to each product run and can be compared to checkweigher batch data, which potentially helps isolate smaller contaminated batches that need to be recalled, instead of an entire production run.

 The absence of good product inspection can endanger patient health and safety. Such incidents can lead to major legal action being taken. Even without a worst-case scenario such as major legal action being taken; however, there is still danger posed to a pharma brand. For example, in the United States, says Pipe, pharma producers that fall foul of FDA 21 

) Part 210 (Current Good Manufacturing Practice in Manufacturing Processing, Packing, or Holding of Drugs) (2) and 21 

 Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals) (3) are issued warning letters that are publicly available. The issuance of a warning letter can impact public trust in the brand and the brand’s reputation in the industry as well as cause extra delays and costs in bringing products to market.

 Because the pharmaceutical industry is highly regulated, compliance is critical for both patient safety and the furtherance of responsible drug supply. Quality assurance programs should therefore be robust and comprehensive, with risks identified and mitigated, Pipe says. The requirements specified in FDA’s 21 

 Parts 210 and 211 include that pharma producers must take steps to protect against contaminants getting into products and protect against damaged or compromised products reaching the market. “X-ray technology can play a key part in helping to ensure compliance, for the reasons already listed above. In addition, modern X-ray inspection systems keep digitalized records of activity, helping producers to meet the demands of 21 

 Part 11 (i.e., audit trails and digital signatures) (4),” Pipe adds.

The advantages offered by automated visual inspection include speed, precision, and consistency. An automated system can quickly process large volumes while at the same time detecting small defects, which can be missed in a manual inspection (5).

It is important to note that automated vision inspection systems have their own limitations, namely that the system’s performance is only as good as its programming. For instance, if the system has been programmed to account for every possible variation in inspection conditions, then there is a risk that it may erroneously flag safe products as defective (6). Meanwhile, there are practical considerations that may hinder widespread implementation of automated vision inspection systems across all operational scenarios. Contract development and manufacturing organizations may encounter challenges, for example, when justifying the capital investments needed (significant capital investments) and associated validation processes for implemented automated inspection. Justifying implementation could be particularly difficult when dealing with products manufactured in small batches or products that have infrequent production cycles (7).

1. Grand River Aseptic Manufacturing. Finished Product Inspection: Automation, Complex Therapeutics, and Quality Standards. 

 (Government Printing Office, Washington, DC).
3. 

 (Government Printing Office, Washington, DC).
4. 

 (Government Printing Office, Washington, DC).
5. Marsale, T. Balancing Act: Human vs. Machine Inspection in Pharmaceutical Manufacturing. 

 online, Oct. 18, 2023.
6. Yadav, V.; Kennedy, C. Vision Inspection Using Machine Learning/Artificial Intelligence. 

. November/December 2020.
7. Melchore, J. A. Sound Practices for Consistent Human Visual Inspection. 

 (1), 215–221. DOI: 10.1208/s12249-010-9577-7

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Vol. 48, No. 8
August 2024
Pages: 29–30

When referring to this article, please cite it has Mirasol, F. Considerations for Finished Product Inspection Systems. 

Manual and automated inspection technologies have their own advantages and limitations.

Considerations for Finished Product Inspection Systems

On Aug. 1, 2024, Freudenberg Medical announced  an expansion to its biopharma product portfolio, which now includes custom single-use assemblies. The assemblies will be combined with the company’s expertise in silicone extrusion and molding. Included in the new offerings are single-use Y-connector manifolds, tubing assemblies, and bottle cap assemblies with multiple inlets/outlets. Both labs and current good manufacturing practice (CGMP) bioprocesses commonly use bottlecap assemblies with Y-connector tubing for critical fluid transfer applications, according to the company in a press release.

The assemblies are cleanroom manufactured according to customer specifications. Among the advantages, Y-connector overmolds offer unobstructed flow within a critical fluid path and can prevent leaks from occurring. Leaks are commonly seen with standard fluid couplings, fittings, and connectors, according to Freudenberg. “Validated production processes with proven process capabilities will continuously ensure consistent overmolding of Y-manifolds on customer-specified tube ends,” the company stated in the press release.

The expanded biopharma portfolio complements the company’s existing PharmaFocus Premium product line containing high purity, platinum-cured silicone tubing and sanitary ends for single-use systems. The company’s tubing, molded components, and systems are used in bioprocessing, biotechnology, lab processes, GMP manufacturing, small batch processes, and cell and gene therapy as well as for the production of messenger RNA, biosimilars, and regenerative proteins.

The company’s other expansion activities include a $50 million investment in a new Hemoteq AG production facility in Aachen, Germany, to expand its coatings business (1) and a $25 million investment to establish a manufacturing site in Costa Rica (2). The expansion in Germany, which Freudenberg announced in June 2024 will triple its manufacturing footprint with a new 130,000-ft

 facility in Alsdorf, near the existing site. The new facility houses ISO Class 7 cleanrooms, laboratories, and offices and will serve as a hub for R&D and production as well as drive innovation in medical coatings (1).

The new Costa Rica facility, announced in February 2024, is slated to come online in the beginning of 2025 and will be dedicated to assembling high-volume minimally invasive catheters for electrophysiology, vascular and structural heart therapies, and other medical devices requiring high-precision manual assembly. The first phase of construction comprises a build on 50,000 ft

 and the facility will house three ISO 7 cleanrooms. The company also expects to add another 50,000 ft

 to the site within three years of its opening. This added construction will quadruple Freudenberg’s total footprint in Costa Rica (2).

Of the Germany site expansion, Mark Ostwald, CEO of Freudenberg Medical, said in a company press release issued at the time, "The convergence of medical devices and drugs is inspiring a new generation of innovative products that fundamentally improve patients’ outcomes. With this innovation driven investment, we are strengthening our position as a strategic partner to our customers, offering vertically integrated solutions along the entire supply chain" (1).

Meanwhile, Róger Gómez, vice-president/general manager of Freudenberg Medical in Costa Rica, said of the Costa Rica facility expansion at the time it was announced, “The investment in this new site underlines Freudenberg Medical’s confidence in Costa Rica as an integral part of our global growth strategy. In the next three years, we will triple the number of employees from the current 300 to over 900 team members. Committed to diversity and inclusion, we offer equal opportunities to all” (2).

1. Freudenberg Medical. Freudenberg Medical Expands Coatings Business with New Production Facility. Press Release, June 11, 2024.
2. Freudenberg Medical. Freudenberg Medical Establishes Second Production Facility in Costa Rica. Press Release, Feb. 14, 2024.

Freudenberg Medical has introduced custom single-use assemblies for silicone extrusion and molding for biopharma applications.

Freudenberg Expands Biopharm Product Portfolio with Addition of Custom Single-Use Assemblies

AbbVie has completed its acquisition of Cerevel Therapeutics, a clinical-stage biopharmaceutical company specializing in neuroscience diseases. Cerevel is now a part of AbbVie, AbbVie announced in an Aug. 1, 2024  press release. The acquisition, which AbbVie initially announced in December 2023, is valued at $45 per share in cash, or a total equity value of approximately $8.7 billion (1).

"AbbVie's acquisition of Cerevel strengthens our foundation in neuroscience and positions us to deliver sustainable long-term performance into the next decade and beyond," said Robert A. Michael, chief executive officer, AbbVie, in a company press release. "Our new Cerevel colleagues share our commitment to deliver meaningful change for patients living with neurological and psychiatric conditions. We are excited to welcome the talented Cerevel team to AbbVie."

Under the acquisition, AbbVie gains Cerevel's pipeline, which comprises multiple programs across several neurological and psychiatric conditions with significant unmet need, including schizophrenia, Parkinson's disease, and mood disorders. According to the press release, Cerevel's pipeline complements AbbVie's existing neuroscience portfolio.

Among Cerevel’s promising drug candidates is emraclidine, a potential best-in-class, next-generation antipsychotic. Emraclidine is a positive allosteric modulator (PAM) of the muscarinic M4 receptor that is currently being studied for treating schizophrenia. A Phase Ib study showed that emraclidine demonstrated promising efficacy and safety. It is currently completing two Phase II trials.

Tavapadon is a first-in-class dopamine D1/D5 selective partial agonist for managing Parkinson's disease. This late-stage drug candidate is currently in Phase III studies and has the potential to work as both a monotherapy and an adjunctive treatment. The efficacy and safety-tolerability profile for tavapadon could enable its utility in treating early Parkinson's disease and can be complementary to AbbVie's existing symptomatic therapies for treating advanced Parkinson's disease, according to the press release. Tavapadon met its primary endpoint in a pivotal Phase III study, and data from additional Phase III trials are anticipated to come out later this year.

Meanwhile, CVL-354 is a potential best-in-class kappa opioid receptor (KOR) antagonist currently in Phase I development. This drug candidate can potentially provide significantly improved efficacy and tolerability compared to existing treatments for major depressive disorder (MDD). Finally, darigabat, currently in Phase II development, is an alpha 2/3/5 selective γ-aminobutyric acid type A receptor PAM for treatment-resistant epilepsy and panic disorder.

The acquisition of Cerevel marks an additional multibillion-dollar transaction AbbVie has completed within this year. In February 2024, the company completed its acquisition of ImmunoGen (2), a 

 that added promising next-generation antibody drug conjugate drug candidates to AbbVie’s pipeline, boosting AbbVie’s presence in solid tumor therapeutics (3).

1. AbbVie. AbbVie to Acquire Cerevel Therapeutics in Transformative Transaction to Strengthen Neuroscience Pipeline. Press Release, Dec. 6, 2023.
2. AbbVie. AbbVie Completes Acquisition of ImmunoGen. Press Release, Feb. 12, 2024.
3. AbbVie. AbbVie to Acquire ImmunoGen, including its Flagship Cancer Therapy ELAHERE (mirvetuximab soravtansine-gynx), Expanding Solid Tumor Portfolio. Press Release, Nov. 30, 2023.

This acquisition gives AbbVie clinical-stage assets from Cerevel’s pipeline that complement AbbVie's emerging neuroscience pipeline and branded products for treating psychiatric disorders, migraine, and Parkinson's disease.

AbbVie Strengthens Neurological Pipeline with $8.7 Billion Acquisition of Cerevel Therapeutics

A new biotech company, Third Arc Bio, which specializes in the development of multifunctional antibodies that are optimized for T cell engagement across solid tumors and inflammatory and immunology (I&I) diseases, has raised $165 million in oversubscribed Series A financing. The company plans to use the funds to advance its drug development programs in clinical studies that address significant unmet needs in oncology and autoimmunity, Third Arc Bio announced in a July 23, 2024 company press release.

Since its initial launch in 2022 with seed financing from Omega Funds, the company has advanced multiple programs that are anticipated to enter the clinic starting in early 2025. The company’s leadership team has collectively brought 19 drugs to market from the discovery and development phases.

“With a powerful discovery engine and a stellar development team, the company is well-positioned to deliver best-in-class therapies and regimens,” said Peter Lebowitz, MD, PhD, CEO of Third Arc Bio, in the press release. “We are grateful for the strong support from Omega Funds and our investor syndicate, who believe in the value of our precise and targeted approach to modulating the immune response with advanced biologics.”

Third Arc Bio’s leadership team consists of:

Peter F. Lebowitz, MD, PhD, who joined as Third Arc Bio’s CEO in January 2024. Lebowitz has extensive drug development experience in his prior role as global head of Oncology R&D at Johnson & Johnson, which achieved 13 major new drug approvals with first and best-in-class medicines, according to the press release. Prior to Johnson & Johnson, Lebowitz also served in multiple leadership roles at GSK, including vice-president, global head of Oncology Early Clinical Development, and vice-president, medical development leader in Late Development at GSK. In those roles, he filed 10 investigational new drug applications (INDs) and played a crucial role in the global registration of two oncology medicines.

Sanjaya Singh, PhD, is founder and chief scientific officer of Third Arc Bio and has more than 25 years of experience in biotherapeutics. He has co-invented multiple immunology and immuno-oncology compounds, including risankizumab (Skyrizi). Singh’s prior roles include global head of Janssen Biotherapeutics, Johnson & Johnson, as well as at Boehringer Ingelheim, Biotherapeutics Discovery, and Tanox (acquired by Genentech). He is co-founder and scientific advisory board member of Aliada Therapeutics.

Joe Erhardt, PhD, chief operating officer, Third Arc Bio, has served for more than 20 years in roles ranging from early discovery through to late clinical development. He most recently served as vice-president, global head of Oncology Discovery and External Innovation, Johnson & Johnson. In his prior roles, Erhardt had operational oversight of expansive portfolios as well as licensing and collaboration for oncology discovery and early development. He has delivered a significant number of internal and external candidates in discovery and clinical pipelines across different modalities, including T cell redirection, T cell co-stimulation, antibody drug conjugates, and targeted radiotherapy.

“The Third Arc Bio team has an outstanding track record of developing impactful medicines, including multiple approved drugs that have redefined standard-of-care in oncology and I&I,” said Arjun Goyal, MD, co-founder and managing director of Vida Ventures, which led the Series A financing, in the press release. “We are tremendously excited to lead this round alongside a high-caliber syndicate of life science and strategic investors at a pivotal time for the company’s growth. With Third Arc’s leading portfolio of best-in-class biologics, multiple INDs planned for 2025, and an extraordinary team of drug developers, the company is poised to create bold new treatments leveraging T cell biology for patients globally.”

Engineered T cells are emerging as highly effective treatments, particularly for hematological cancers. This is evidenced by the hundreds of clinical programs that are underway to expand the efficacy, safety, and applications of this modality, otherwise known as a “living drug” (1).

1. Kirouac, D.C.; Zmurchok, C.; Morris, D. Making Drugs from T cells: The Quantitative Pharmacology of Engineered T Cell Therapeutics. 

With the Series A funding, the new biotech company will advance the development of enhanced biologics for treating solid tumors and inflammatory and immunology diseases.

Third Arc Bio to Advance Biologic Drug Development Programs on $165 Million Funding 

STADA and Alvotech have launched Uzpruvo in Europe, marking the first approved biosimilar to Stelara (ustekinumab) in the European market, according to a July 22, 2024 company press release. Uzpruvo is now available across a majority of European countries, including the largest markets in the region where pricing and reimbursement approvals have been secured to ease the biosimilar’s market entry. 

This launch follows close on the heels of the expiry of exclusivity rights related to the European reference molecule patent. The availability of a biosimilar ustekinumab offers expanded access to patients, physicians, and payers for a therapy to treat certain indications in the gastroenterology, dermatology, and rheumatology disease areas. The companies expect to conduct additional launches in other European countries over the coming months following national price approvals and utilizing a fully European supply chain, according to the press release.

“Launching Uzpruvo at the earliest opportunity in Europe’s largest pharmaceutical markets promotes access by creating competition,” stated Peter Goldschmidt, STADA’s CEO, in the release. “This opportunity to improve patient access through wider usage of a life-changing biological treatment emphasizes STADA’s purpose of Caring for People’s Health as a Trusted Partner.”

The European Commission approved Uzpruvo in January 2024, making the product the first ustekinumab biosimilar to be approved in Europe with equivalent efficacy, safety, pharmacokinetics, and immunogenicity to the reference biologic, Stelara (1). Uzpruvo is indicated for treating Crohn’s disease and psoriatic arthritis in adults and for treating plaque psoriasis in adults and children aged from six years. Uzpruvo is not currently approved to treat ulcerative colitis, however, because the originator biologic still holds exclusivity in this indication.

“With comparable safety, efficacy, and immunogenicity, Uzpruvo gives clinicians an opportunity for a seamless and simple switch for their patients, who can benefit from a thinner needle and latex-free syringe,” commented Bryan Kim, STADA’s Global Specialty head, in the press release.

Uzpruvo is offered in a pre-filled syringe that has a thinner needle than the reference biologic. The biosimilar is also latex-free to minimize the risk of allergic reactions. According to the companies, Uzpruvo was developed and is manufactured and packaged wholly within Europe. It has a shelf life of 36 months.

Ustekinumab is the second immunology biosimilar to reach the market through the STADA and Alvotech partnership. In December 2022 the companies launched Hukyndra a high-concentration, citrate-free adalimumab therapy, a biosimilar to Humira, on the European market (2).

Meanwhile, in June 2024, the partners expanded their collaboration by entering into a development, manufacturing, and marketing alliance for a proposed biosimilar candidate to Prolia/Xgeva (denosumab), a human monoclonal Immunoglobulin G2 antibody for treating osteoporosis in women and bone loss in men (3,4). Under this agreement, Alvotech is responsible for the development and manufacturing of biosimilars within the partnership at its Reykjavik, Iceland, facility.

Union Register of Medicinal Products for Human Use

 (accessed July 29, 2024).
2. Alvotech. Alvotech and STADA Broaden Access to Hukyndra Adalimumab Biosimilar in Europe. Press Release, Dec. 7, 2022.
3. Alvotech. Alvotech and STADA Add to Strategic Alliance Through Denosumab Partnership. Press Release, June 11, 2024.
4. EMA. 

STADA and Alvotech have launched Uzpruvo in Europe, making it the first approved biosimilar to Stelara (ustekinumab) in the European market.