Digital Transformation in Pharma Manufacturing

Patent Cliff Deals, Tariff Pressures, and the In Vivo Cell Therapy Bet

Behind the Headlines, Episode 23

ICH Q12 and Post-Approval Changes

Speed, Flexibility Top Large-Molecule Manufacturing Trends

Drug Digest July 2025

Key Insights from Industry Survey Results

Bio/Pharma's Tariff Response

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

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Tecelra (afamitresgene autoleucel), a first-of-its-kind gene therapy for the treatment of synovial sarcoma made by Adaptimmune, was approved by FDA on Aug. 2, 2024 for use in adults with an unresectable or metastatic case of this rare form of cancer and who have received prior chemotherapy, are positive for certain human leukocyte antigens (HLA), and whose tumor(s) may express melanoma-associated antigen (MAGE)-A4 as determined by a diagnostic device (1).

According to a press release from FDA, Tecelra is also the first FDA-approved T-cell receptor (TCR) gene therapy, an autologous immunotherapy composed of a patient’s own T cells, which are modified to express a TCR that targets MAGE-A4 (1). As an immune system trigger, that antigen is normally expressed by cancer cells in synovial sarcoma; among the other antigens for which Tecelra patients may be positive are HLA A*02:01P, -A*02:02P, -A*02:03P, and -A*02:06P.

Synovial sarcoma, which affects about 1000 people annually in the United States, most of them adult males under the age of 40, is a cancer in which malignant cells develop and form into a tumor in soft tissue, most often in the extremities, although it can be found in all parts of the body, and cancerous cells can spread throughout the body as well (1). It is treated with surgery to remove the tumor, followed by radiotherapy and/or chemotherapy if the tumor is large, has returned after being removed, or has metastasized.

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in FDA’s Center for Biologics Evaluation and Research (CBER), in the press release. “Today’s approval represents a significant milestone in the development of an innovative, safe, and effective therapy for patients with this rare but potentially fatal disease.”

FDA’s Accelerated Approval pathway provided Tecelra with an opportunity to be approved while Adaptimmune conducts further trials to verify the therapy’s predicted benefit, and one such confirmatory trial is currently ongoing (1). Accelerated Approval allows FDA to move certain drugs forward for treatment of conditions or diseases that are serious or life-threatening and have an unmet medical need, and for which the drugs’ effects on surrogate endpoints have been beneficial (2). In a multicenter, open-label clinical trial, Tecelra produced a response rate of 43.2% among 44 patients, with six months as the median duration of response, according to FDA.

“Potentially life-threatening cancers such as synovial sarcoma continue to have a devastating impact on individuals, especially those for whom standard treatments have limited efficacy due to tumor growth and progression,” said Peter Marks, MD, PhD, director of the CBER. “The approval of this state-of-the-art immunotherapy technology provides a critical new option for a patient population in need and demonstrates the FDA’s dedication to the advancement of beneficial cancer treatments.”

1. FDA. FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma. Press Release. Aug. 2, 2024.
2. FDA. Accelerated Approval. 

Articles

Synovial sarcoma is a rare form of cancer impacting about 1000 adults in the United States each year, most of them men in their 30s or younger.

First Gene Therapy for Adults with Metastatic Synovial Sarcoma Approved by FDA

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Contract organizations offer sponsor companies flexibility by providing capacity, expertise, knowledge, and cost savings. Contract manufacturing organizations (CMOs), contract development and manufacturing organizations (CDMOs), and other contract organizations can also offer smaller bio/pharma companies greater opportunities, by providing the resources smaller biopharma companies may not have. According to Robert O’Brien, director operations—Packaging & Logistics at Almac Pharma Services, sponsor companies should consider if contracting activities to a CMO is more cost effective than performing those activities in-house. O’Brien points to direct access to specialists and equipment, a level of control of quality standards, and requirements for scale up as factors to consider when deciding whether to outsource or not. “Outsourcing enables the sponsor company to concentrate on their core competencies, product innovation, and strategic initiatives,” O’Brien says.

When making the decision to outsource a particular process to a contract partner, there are several things sponsor companies should consider. Tech transfer is an important step when outsourcing to a CDMO and should be evaluated when choosing to outsource processes, specifies Peter Ercoli, chief operating officer, Biologics, at BIOVECTRA. Ineffective tech transfers can lead to persistent complications, adds Ercoli. “Conversely, sponsors should ensure their processes are completely defined before initiating a tech transfer, unless they want the CDMO to define it for them. In the case where sponsors are leaning on the CDMO to define their tech transfer process, both parties must be clear on this understanding from the outset,” he says.

Not following regulatory requirements can also complicate the situation when working with CDMOs, according to Ercoli. “The last thing a sponsor wants is to successfully complete the tech transfer and scale-up phases only to fail a pre-approval inspection. Such a failure can be catastrophic, potentially setting back the project by months or even years. While other challenges can be managed with guidance or collaboration, the readiness of facilities and personnel for regulatory inspections is non-negotiable and must be thoroughly vetted,” he says.

The benefits of an outsourcing partner extend to most, if not all, aspects of development and manufacturing, and analytical testing is no different. “CDMOs amass a great breadth and depth of knowledge through their exposure to a wide range of product types including small molecules, peptides, biologics, conjugates, highly potent, and controlled substances,” says Susan Hackett, associate director—Technical Operations, Almac Sciences. “Additionally, not all companies have the appropriate infrastructure to accommodate analytical testing; therefore, outsourcing these operations to an established CDMO helps to save time and cost.”

Outsourcing finished product testing is beneficial for sponsors, because it can provide unbiased results, according to Shailesh Vengurlekar, senior VP Quality & Regulatory Affairs, at LGM Pharma. Sponsor companies should consider the quality of the work and the data provided by a contractor when selected a testing partner. Turnaround time, infrastructure, cost, and communication are also key, according to Vengurlekar.

“Sponsors typically benefit most when outsourcing complex testing services that they may not have the capability (equipment, personnel expertise, time, etc.) to perform in-house,” says Vengurlekar. “[Whereas], it is also beneficial to sometimes outsource simple and routine testing involving a lot of the sponsor’s time and labor. The time can be better utilized by the Sponsors to develop their product database as well as on timely submissions to meet company goals.”

A robust methodology can be achieved by outsourcing method development and validation, remarks Hackett. “As the drug develops, working with a provider who has a dedicated team utilizing orthogonal techniques such as mass spec[trometry], ID testing, can be hugely beneficial and help to resolve any issues much quicker,” says Hackett. “For finished product testing, outsourcing to a partner who has the capability, capacity, and resources to manage all testing aspects together can alleviate many of the issues which inherently arise during drug development.”

Hackett stresses that both the sponsor and the contractor are responsible for analytical testing and should maintain good communication. “Ensuring that there is equivalent equipment between the labs is an obvious solution, and that the methods are fully understood by both teams,” she says. “Robust processes, particularly with method transfer and familiarization, should also ensure the chances of success. However, as stated, having access to a team who are well experienced in orthogonal techniques can be hugely beneficial if [testing failures] occur to conduct deeper analysis to troubleshoot and find a resolution,” says Hackett.

“[Testing results] may vary [from sponsor to contractor] if the method transfer has been incorrectly performed or same methodology/equipment are not used by testing laboratories. Significant variations or laboratory errors are observed due to lack of proper training, poor quality of protocols, or detailed procedures,” says Vengurlekar. “Typically, collaboration between both parties is required to investigate the results from both ends to determine the true value. The sponsor should always take the lead to investigate the root cause and guide contractor labs to put appropriate corrective and preventive actions (CAPAs) in place.”

Packaging is one of the final steps when manufacturing a bio/pharmaceutical product and sending it out to the market. The quality of a product can be compromised by a variety of factors, including temperature; therefore, O’Brien notes that packaging materials should be carefully selected. Other challenges include labeling and serialization requirements.

Packaging providers can provide cost savings by sparing a sponsor from having to invest in equipment, facilities, personnel, and a broad network of suppliers, according to O’Brien. Contractors may offer state-of-the-art technology and staff training, he states. “[O]utsourcing allows sponsors to achieve scalability and flexibility, enabling them to scale their packaging operations up or down based on demand. This flexibility is crucial for adapting to market fluctuations and growth opportunities,” O’Brien states.

Contracting out packaging services can also offer a layer of quality control. Contract packagers offer experience with regulations in various territories and can help ensure safety and quality standards are correctly met, specifies O’Brien. “External partners often have robust quality control systems in place. This ensures that packaging adheres to industry and highest quality standards ensuring products maintain stability throughout the supply chain,” he says.

When partnering with a contract packager, O’Brien stresses that specifications, timelines, and quality standards must be aligned with both parties. “Risk management is a key concern—it’s vital to mitigate potential disruptions to the supply chain that may arise due to unforeseen events. Quality control is similarly critical—consistency and compliance across the packaging process must be maintained. Cost management—balancing cost-effectiveness with quality—is a perpetual consideration,” says O’Brien. “Lastly, intellectual property protection must be addressed to safeguard proprietary information during collaboration. Overall, these challenges can be overcome through close collaboration, transparency, and clear agreements between both parties to ensure successful outcomes.”

Partnerships don’t always work out. But what if that partnership is the development and/or manufacture of an important drug product? If a sponsor company must change from one contract manufacturer to another when a project is already underway, what challenges may they face? Transferring mid-project from one contract to another requires close coordination, according to O’Brien, to minimize delays and costs.

“Proactive planning and open communication including full, and early, transparency regarding any concerns, is key to overcoming these challenges,” says O’Brien. “In addition, rigorous quality control measures are essential to ensure consistent quality between the existing and new provider. Finally, internal and partner teams should be cautious and thorough when migrating data, documentation, and intellectual property to avoid delays and errors during the transition. Both parties need to adjust to new processes, communication channels, and expectations therefore continual briefing, communication and escalation, where required, is essential throughout.”

“When switching from one CDMO to another during a project, the new partner or CDMO should be given access to communicate with the innovator directly,” says Ercoli. “This approach allows for a clear understanding of the development context and enables questions to be answered accurately. Direct access to the innovator ensures that the original intent of the project is preserved. Otherwise, transitioning from one CDMO to another often results in miscommunication. The process can resemble a game of ‘telephone’, where information is passed along through multiple intermediaries, leading to potential distortions. By the time the message reaches the new CDMO, the original intent may be lost, complicating the project further. To mitigate these risks, all parties involved should strive to keep open lines of communication as much as possible during the transition.”

Outsourcing can provide a variety of benefits for a sponsor, whether the outsourced service is testing, packaging, manufacturing, or another process in the lifecycle of the product. If a sponsor chooses to outsource work, they should keep quality in mind. Contractors will most likely have several customers; therefore, sponsors should look for customized quality control (1).

“When CDMOs develop quality agreements with a greater focus on client needs, it can increase trust, compliance, and even make audits easier to manage. Complex procedures can be simplified by engaging all parties and clearly documenting in the quality agreement from the start. While this may add initial time and cost, over the long run this will pay out with less process issues, including errors or oversights,” said Iain McGhee (1).

Taking these factors into consideration can help a sponsor company create the best outsourcing strategy for the company, the product, and the patient.

1. McGhee, I. Ensuring Quality in Contracted Support. 

BioPharm International Partnerships for Outsourcing eBook.

®
Vol. 48, No. 8
August 2024
Pages: 31–33

When referring to this article, please cite it as Haigney, S. Contracting Out Frees Sponsors Up. 

Contract organizations offer sponsors specialized equipment, capacity, and expertise for testing, manufacturing, and packaging bio/pharmaceutical products.

Contracting Out Frees Sponsors Up

Cheryl Barton is director of PharmaVision, 

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Over the past two decades, 32 cell and gene therapies (CGTs) have been approved by the regulatory authorities worldwide, and more than 2000 novel products are under clinical investigation (1). However, many patients do not have access to these life-saving therapies, partly due to the complexity and high cost of manufacture (2). But how can CGTs be made more cost-efficient given the high labour and facility costs?

According to Miguel Forte, CEO, of Kiji Therapeutics, France, and president of the International Society for Cell & Gene Therapy, “It is clear that CGTs have the opportunity to deliver enormous value to patients; nonetheless, manufacturing is complex, and it has been challenging to deliver the product. Innovative technologies and services have enabled the industry to move towards an automated, closed-system approach that is easier and safer to operate and is less costly and closer to the patient.”

Cell therapies can be derived ex vivo from autologous cell therapies (patient to patient), allogenic cell therapies (donor to patient), or in vivo cell therapies (cell line to patient). Each approach requires manufacturers to tailor the biomanufacturing process to generate specific cell types (and/or vectors), safely, efficiently, and cost-effectively. Manufacturing tools have tended to lag behind scientific advances in CGTs leading to bottlenecks in cell production. Currently, most CGT manufacturers use disconnected single-step/modular or semi-automated solutions; however, the industry is migrating towards fully automated cell therapy manufacturing processes (3). And this approach could significantly reduce manual intervention, risk of contamination, and human error; improve product quality and speed of delivery; and reduce production costs (4).

According to David Smith, vice president of Development, BioCentriq, “Labour costs, and facility costs are sky high, which have led to high price points, particularly in autologous cell therapies where production is 1:1. Automation is a key part of improving costs, reducing labour both in and outside the clean room, and implementing release by exception can help to reduce bottlenecks. Companies are trying to integrate unit operations whether it’s an ‘all-in-one-box’ approach or a ‘unit-operator’ approach where units can be plugged in or out and are integrated within robotic systems to offer greater flexibility.”

For instance, Lonza’s Cocoon Platform and Miltenyi Biotec CliniMACS Prodigy offer an ‘all-in-one-box’ approach providing a closed, automated system for patient-scale cell therapy manufacturing from cell isolation, activation, transduction/transfection, expansion, and harvest within a validated cell manufacturing system (5,6). CliniMACS Prodigy modular Instruments can also be run in parallel to provide large-scale batch production.

UK-based Ori Biotech launched its IRO platform developed in 2024 in collaboration with CTMC (a joint venture between Resilience and MD Anderson Cancer Center). This platform automates the activation, transduction, expansion, and harvest of a wide range of cell types to rapidly scale up manufacturing from the clinic to the commercial setting (7).

Paris-based Astraveus SAS has developed the Lakhesys Benchtop Cell Factory, an end-to-end solution for the manufacture of adherent, non-adherent, and inducible pluripotent stem cells (iPSCs) (8). The company has raised €16.5 million in seed financing and received a €10.4 million grant from the French government as part of its “Innovation in Biotherapies and Bioproduction” initiative, to advance the development of its technology (9).

Several companies are developing integrated bioreactors, robotic systems, and smart monitoring technologies that can support a ‘unit operator’ approach.

UK-based Cellular Origins, launched Constellation, a closed fully automated, and configurable robotic platform for CGT manufacture in 2023 (10). In May 2023, it forged a partnership with ScaleReddy (a joint venture between Bio-Techne, Fresenius Kabi, and Wilson Wolf) to automate its CGT manufacturing workflow using Cellular Origin’s robotic system (11). According to Jason Jones, Global Business Development lead, Cellular Origins, “Our company integrates existing, proven technologies with mobile robotics to provide fully automated factories that can be scaled up to manufacturers’ requirements, minimize risks, and are GMP [good manufacturing compliance] compliant. We can achieve a 30-fold increase in space efficiency and manufacture and a 16-fold labour reduction, equating to a 51% reduction in cost-of-goods and enabling manufacture 24/7, 365 days a year.”

Swiss-based Limula has taken a different approach and developed a modular solution that combines a bioreactor and centrifuge into one device for on-demand and at-scale manufacturing of cell therapies (12). In May 2024, the company raised CHF 6.2 million (US$6.8 million, €6.24 million) in seed funding to develop its automated CGT manufacturing platform, the funding round was over-subscribed highlighting the interest that venture capitalists have in this field (13).

UK-based MicrofluidX has developed a space-saving stackable multi-bioreactor instrument—the Cyto Engine Stack. Each bioreactor can be controlled and monitored independently, to allow cell therapy manufacturers to expand their manufacturing capacity without increasing the facility footprint. The first Cyto Engine product is scheduled for launch in early 2025 (14).

Other companies have focused on leveraging digital tools and advanced analytics to streamline the manufacturing process. For instance, UK-based Autolomous has launched AutoloMATE Launchpad, a cloud-based CGT platform that allows for the scalability and adaptability of different CGT modalities (15). According to Alexander Seyf, the CEO of Autolomous, “Addressing manufacturing challenges effectively demands a shift towards more integrated and automated systems. By leveraging digital tools and advanced analytics, we can enhance process control, increase reproducibility, and reduce labour-intensive procedures which, in turn, decrease costs significantly. Moreover, digitization can streamline data flow across the manufacturing process, ensuring that critical information is accessible and actionable. This integration leads to improved decision-making, faster turnaround times, and ultimately, more standardized production of therapies.”

In 2024, US-based Cellares, became the first Integrated Development and Manufacturing Organization (IDMO) to offer a high-throughput fully, automated smart manufacturing platform Cell Shuttle. In April 2024, the company signed a US$380 million (€349 million) supply agreement for the manufacture of chimeric antigen receptor-T cell therapies with Bristol-Myers Squibb, and it announced a similar agreement with Kite in June (16,17).

Over the next decade, the demand for CGTs is expected to grow as they move further up the treatment cascade and target more common diseases. It will be essential for companies to address the challenges associated with scaling up the manufacturing process to provide high-quality, consistent autologous and allogenic cell products while adhering to stringent regulatory standards. Fully automated space-saving modular technologies will allow manufacturers to steadily scale up capacity and adapt to demands (18).

Smith notes, “CDMOs [contract development and manufacturing organizations] are looking at the trajectory of pipeline products and questioning where and when they need to invest in new facilities and technologies. Manufacturing is one of the biggest areas of risk in CGT developments, but if we can de-risk the process by deploying robust engineered manufacturing processes and automation, we can reduce the cost of autologous cell manufacture and increase the speed and flexibility to meet individual needs. On the allogenic side, the processes tend to be on a larger scale, and the drug product cost is shared amongst many patients. Although automation can assist in cost reduction, the burden is less steep than for autologous, that said, many of the same automation tools can be used across processes, and the industry is looking to standardize manufacturing.”

In the longer term, the industry could move towards a more decentralized manufacturing model that utilizes automated point-of-care technologies to enable on-sitepreparation of CGTs in or near hospitals, helping to bring therapies closer to the patient.

“The current acute unmet need is on scaling centralized systems, but we’ve had some interesting conversations around decentralization negating operator variability/increasing process comparability and digitalization of information of the product and opening up facilities at the national, regional, and near-hospital levels depending on the therapy and medical need,” observes Jones.

Gene, Cell, and RNA Therapy Landscape Report.

 Q1 2024 Quarterly Data Report. 11 Apr 2024.

Harrison, P.T., Friedmann, T. Correction: Cost of Gene Therapy. Gene Therapy, 2024, 31, 195-196.

Closed, Automated Cell Therapy Manufacturing–Is Your Facility Ready?

Harris, R. Cell Therapy Manufacturing Shifts to Automatic. Genetic Engineering & Biotechnology News. 4 Oct 2021.

The Cocoon® Cell Therapy Manufacturing Platform.

 miltenyibiotec.com (accessed July 2024).

Ori Biotech Unveils IRO Platform at Annual International Society for Cell & Gene Therapy Conference

Lakhesys™ Benchtop Cell Factory - Astraveus - Enable a Healthier Tomorrow

PRNewswire. Astraveus Raises €16.5 Million Series Seed Round to Advance the Development of its Automated, Microfluidic Cell and Gene Therapy Manufacturing Platform. News Release. 27 Jun 2023.

Cellular Origins Launches Constellation™, Its Configurable Robotic Platform to Enable Scalable Manufacture of Advanced Therapies

Cellular Origins Partners with ScaleReady to Simplify, Standardize, and Automate Cell Therapy Manufacturing

The Future of Cell and Gene Therapy is Automated

Limula Raises CHF 6.2 Million in an Oversubscribed Seed Round to Develop an Automated Cell and Gene Therapy Manufacturing Platform

MicrofluidX Secures Innovate UK Award to Advance High Throughput

Autolomous Releases the CGT industry’s First Free eBR Builder, autoloMATE Launchpad, to Empower Digital Planning

Bristol Myers Squibb, and Cellares Announce a $380M Worldwide Capacity Reservation and Supply Agreement for the Manufacture of CAR T Cell Therapies to Bring the Promise of Cell Therapy to More Patients, Faster.

Cellares Announces Agreement with Kite to Evaluate Its Cell Shuttle Automated Manufacturing Platform.

Small Footprint Automated Closed Production Platforms for CAR-T and Other Advanced Therapies

Cheryl Barton, PhD, is director of PharmaVision, 


Vol. 36, No. 7
July/August 2024
Pages: 14–16

When referring to this article, please cite it as Barton, C. Frontrunners in Automated Cell and Gene Therapy Manufacturing. 

Innovative solutions are making personalized cell and gene therapies accessible to all.

Frontrunners in Automated Cell and Gene Therapy Manufacturing

Mike Hennessy Jr. is the Chairman and CEO of 

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This year has indeed been a bountiful year of sport already, with the recent finale to the EURO 2024 soccer competition seeing Spain setting the record for the most titles and the United States co-hosting the T20 World Cup cricket tournament for the first time, to name but a few. However, the most impressive sporting events that have a global audience are the Olympic and Paralympic Games, which are taking place in Paris, France from July 26 until Aug. 11, 2024 and Aug. 28–Sep. 8, 2024, respectively.

Host city Paris has waited 100 years to welcome the Olympic Games back and has never before been the host for the Paralympic Games, which should make for some historic and memorable occasions over the next few months. Sanofi, which is a giant in the field of vaccines and anti-inflammatory treatments, is not usually involved with sporting or cultural events, but has made an exception for the 2024 games being held in the city where the company is headquartered (1).

Younger viewers are increasingly being attracted to watch the games—thanks to the inclusions of sports such as breakdancing and skateboarding—which is something that Sanofi, as a premium sponsor for the 2024 games, hopes to use to its advantage. “We’re using the Olympics to show that we are [cool],” said Josep Catlla, head of corporate affairs at Sanofi, when speaking with Reuters (1).

It is hoped that, through the increased awareness gained from sponsoring the games, the company will be able to attract new talent and remove its conservative image (1). In 2022, Sanofi committed to its ‘ignite the potential in everyone’ campaign for the Paris 2024 games (2). This campaign is aimed at demonstrating the similarities between science and sport, such as overcoming challenges to continue to progress forwards, and to make science inclusive and open to all (3).

We will have to wait and see whether Sanofi’s investment in the Olympics and Paralympics will pay off in the long run with the public or their investors, and whether or not it will be possible to ignite the potential of pharma for the next generation of scientists.

1. Naidu, R.; Burger, L. Drugs Group Sanofi Makes Olympic Jump in Rebrand Bid. Reuters, Jan 10, 2024.
2. Sanofi. Sanofi Commits to Ignite the Potential in Everyone. 

Mike Hennessy Jr is president and CEO of MJH Life Sciences®

When referring to this article, please cite it as Hennessy, M. Igniting Pharma’s Potential. 

Will Sanofi’s plan to recruit the younger generation through its participation in the upcoming 2024 Olympic and Paralympic Games, being held in Paris, pay off?

Igniting Pharma’s Potential?

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

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It is rare indeed for the European Commission (EC) to go against the decision of the European Medicines Agency (EMA); however, for Spanish pharmaceutical company, PharmaMar, such a rare occasion has become a reality.

Six years ago, in July 2018, the EC implemented its decision to reject the marketing authorization application of PharmaMar’s multiple myeloma treatment, plitidepsin (Aplidin), in concurrence with the opinions of EMA’s Committee for Medicinal Products for Human Use (1). PharmaMar contested the decision and filed a lawsuit against the EC, aimed at getting the rejection decision annulled (2).

After being assessed in the General Court of the European Union (EU) in 2020, PharmaMar’s claim that there was a conflict of interest in the experts appointed to assess plitidepsin by EMA was upheld. However, the decision was appealed before the EU Court of Justice, and three years on, in July 2023, the 2020 judgement was set aside, and the case was referred back to the General Court of the EU to rule again (3).

In July 2024, PharmaMar received notification that the EC had revoked its refusal to grant marketing authorization for its multiple myeloma treatment as a result of a member of the EMA’s scientific advisory group’s conflict of interest (2). This is unusual, not least because of the rarity of such an occurrence happening, but also because the EC did not wait for the final judgment of the General Court (4).

And this is not the only case in progress pertaining to conflicts of interest within EMA advisory committees. French independent pharma company, D&A Pharma, has also had the refusal decisions of EMA and the EC for its alcohol dependency treatment sodium oxybate (Hopveus) overturned in court (5).

For now, EMA will need to re-evaluate plitidepsin with absolute impartiality; whether such actions will become more commonplace in the future remains to be seen, but if they do, the integrity of the regulatory authority for Europe could be called into question.

Commission Implementing Decision of 28.6.2024 Revoking Decition C(2018) 4831 (final) Refusing Marketing Authorization Under Regulation (EC) No. 726/2004 of the European Parliament and of the Council for “Aplidin–Plitidepsin”, a Medicinal Product for Human Use

. Brussels, Belgium, 28 June 2024.
2. PharmaMar. Aplidin Will Be Re-evaluated by the EMA. The European Commission Revokes the Decision that Initially Denied PharmaMar’s Marketing Authorization for Multiple Myeloma due to a Conflict of Interest. Press Release, 8 July 2024.
3. EMA. Aplidin. 

 (accessed 4 Aug. 2024).
4. Miñano, L. Deadly Prices: European Commission Rejects Cancer Drug Removal over ‘Impartiality’ Concerns. 

, 22 July 2024.
5. D&A Pharma. The Court of Justice of the European Union Overturns the Decision to Reject the Marketing Authorization for Hopveus: A New Hope for Patients. Press Release, 27 March 2024.

When referring to this article, please cite it as Thomas, F. Demanding Impartiality. 

Potential conflicts of interest with advisory group members have led to EMA’s impartiality coming into questioned for some marketing authorization decisions. 

Demanding Impartiality

Feliza Mirasol is the science editor for 

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

Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.

Q: I am working on making our quality control test laboratory methods more sustainable and environmentally friendly. Do I need to let the regulatory authorities know I am undertaking this initiative?

A: This is a great initiative. Focusing on methods that minimize waste and eliminate the use of hazardous substances is in line with current industry and regulatory trends. Global regulatory authorities have long-term initiatives to encourage quality control (QC) laboratories to adopt sustainable methods within their companies. For example, the 

) has an initiative to remove the rabbit pyrogen test from the Ph. Eur. by 2026.

While you don’t need to inform the regulatory authorities of the initiative during the feasibility phase of exploring alternative methods utilizing sustainable technology, you will need to inform them of your intent to implement these methods when you are ready to use them as your primary methods for evaluating excipients for manufacturing and for releasing the final product for patient use.

One strategy for implementing sustainable testing for monographed items is to submit your test procedure along with the appropriate validation and comparability results to the compendial authorities showing the new method to be equivalent or better than the current existing test method(s). If the compendial authorities adopt the new procedure as part of the official monograph, and, assuming you have indicated in your filing that you follow the current compendia(s), you can just implement the change, noting the adoption of the new compendial procedure in the annual report per Appendix B in FDA’s 

Guidance for Industry, CMC Postapproval Manufacturing Changes To Be Documented in Annual Reports

, which states “Any change made to comply with the official compendium, except relaxation of an acceptance criterion or deletion of a test (see 21 

The drawback to this approach is the unknown amount of time it may take the proposed change to work its way through the monograph revision process and become officially adopted. This approach could take years, and there is no guarantee that it will be successful because the global pharmacopoeias are not harmonized.

The filing requirements when implementing new test method changes to proprietary items can also be accomplished in an annual report, if you submit it as an alternate procedure according to the aforementioned document, according to the FDA guidance, which says, “For drug substance and drug product, the addition or revision of an alternative analytical procedure that provides the same or increased assurance of the identity, strength, quality, purity, or potency of the material being tested as the analytical procedure described in the approved application or deletion of an alternative analytical procedure. The appropriate validation and comparability results against the original procedure will still need to accompany the annual report” (1).

Sustainable product safety tests are straightforward to conduct, but, before implementing them, the company must make sure they are sufficiently validated and yield comparable results to the original method, in addition to notifying the relevant regulatory bodies.

Guidance for Industry, CMC Postapproval Manufacturing Changes to Be Documented in Annual Reports

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates.

When referring to this article, please cite it as Schniepp, S.J. Going Green: Updating Your Filings.

The implementation of new quality control methods must be reported to regulators, says Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates. 

Going Green: Updating Your Filings

ROSS FDA-3500 dual shaft mixer | Image Credit: Charles Ross & Son Company

The ROSS line of Dual Shaft Mixers are robust, versatile systems with enough power to batch dispersions, suspensions, and emulsions with viscosities up to several hundred thousand centipoise. The custom-built ROSS FDA-3500 has a maximum working capacity of 3500 gallons, a two-zone stainless-steel dimpled jacket for heating/cooling, a 4-inch pneumatic discharge valve, and an explosion-proof load cell system rated for up to 20,000 lbs.

This multi-agitator system is equipped with independently controlled drives and is designed to efficiently produce good turnover and impart shear to a viscous batch. Powered by a 300 HP TEFC inverter duty motor, the high-speed disperser runs at tip speeds up to 5000 ft. per minute, inducing high shear forces. Meanwhile, the 60 HP Three-Wing Helical Anchor Agitator feeds product towards the disperser blade and ensures that the mixture is constantly in motion. Teflon scrapers on the anchor wipe materials from the vessel wall, enhancing heat transfer from the jacket.

The ROSS FDA-3500 dual shaft mixer is equipped with independently controlled drives and is designed to efficiently produce good turnover and impart shear to a viscous batch.

Dual Shaft Mixers with Multi-Agitator System

GEA Pharma & Healthcare has introduced NexGen Press 45, the latest member of its NexGen Press line of tablet presses. The larger NexGen Press 45 builds on the previous NexGen Press 30 version and offers the same benefits as the smaller generation, including flexibility to adapt to any containment level (up to occupational exposure band 5 [OEB5]), which is attributed to the FAST CHANGEOVER Exchangeable Compression Module (FCO ECM). The new press can also be equipped with the same option packs as the previous version, enabling agile production and making it a system that can be tailored to accommodate a wide range of tableting applications (e.g., multi-unit pellet system, bilayer, poorly flowing products, high yield, microtablets, etc.). Additionally, the system can accommodate different cleaning strategies (wash offline or inline). A further advantage of the NexGen Press range is that every machine is equipped with six compression modes and each benefits from GEA’s unique Air Compensator technology, which effectively reduces common compression issues.

The NexGen Press 45 is the latest member of GEA Pharma & Healthcare’s NexGen Press line of tablet presses.

Next-Generation Tablet Press

Syngene International, a contract research, development, and manufacturing organization (CRDMO), now offers a new protein production platform aimed at rapid protein synthesis. The platform uses a cell line and transposon-based technology that Syngene licensed from ExcellGene, a Switzerland-based service provider specializing in mammalian cell line development. 

Editor’s note: this article was published in the Aug. 1, 2024 issue of 

The new protein synthesis platform, combined with Syngene’s clone selection and development processes, offers significant improvement in efficiency and precision. The platform offers faster preclinical and clinical development and shorter timelines to product launches, shortening time to market. Advantages include up to 10 weeks reduction in time versus traditional cell line development methods; better predictability and protein yields, with high-titer levels of up to 10 g/L achieved; support for a variety of modalities, including monoclonal antibodies, biosimilars, bispecific antibodies, antibody drug conjugates, and other recombinant proteins. In addition, the platform’s versatility facilitates integration with perfusion and fed-batch manufacturing processes.

Syngene’s protein production platform uses a cell line and transposon-based technology licensed from Switzerland-based ExcellGene.

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