Behind the Headlines Episode 27

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

Artificial intelligence, machine learning, and novel instruments are helping drug developers.

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

®, Susan Schniepp, distinguished fellow, Regulatory Compliance Associates, and co-chair of board of directors, Parenteral Drug Association, expands on the importance of maintaining a robust quality management system (QMS) in bio/pharmaceutical manufacturing. Schniepp hosts an interactive session on the impact of QMS on quality maturity at INTERPHEX, held in New York City on April 16–18, 2024.

For advanced therapy medicinal products (ATMPs) in particular, Schniepp emphasizes how fast-moving this sector is. “The regulations don't keep up with the ATMPs. That technology, and their way of thinking, is turning over quicker than the regulations,” she says.

“The changes in the regulations that are going to come are going to be around quality culture and maintaining a robust quality management system,” she adds. Ensuring documentation and keeping equipment calibrated are important practices to apply to these new fast-moving ATMPs, she states. Schniepp does not necessarily expect to see many changes in the regulations around ATMP development and manufacturing but thinks that there will likely be more guidance documents issued in the future, with one of FDA’s focuses being its quality management maturity model.

“There are some regulations out there that call out quality culture. In particular, the World Health Organization has one on data integrity. It has a definition and standard[s] on what quality culture is,” Schniepp says. She points out that a new aspect of her presentation at INTERPHEX this year is its interactive component, in which she sets up a scenario involving an audit where an incident occurs. She gives the audience three potential responses to discuss, but rather than simply asking them which response do they pick or which response is correct, she instead asks what does the chosen response say about that person or that company’s QMS and the maturity of that system?

Susan Schniepp, distinguished fellow, Regulatory Compliance Associates, demonstrates QMS impact on quality maturity at INTERPHEX.

Susan Schniepp of Regulatory Compliance Associates Explores the Impact of QMS on Quality Maturity (INTERPHEX 2024)

Videos

Susan Schniepp, distinguished fellow, Regulatory Compliance Associates, and co-chair of board of directors, Parenteral Drug Association, demonstrates QMS impact on quality maturity at INTERPHEX.

Experts in sterile processing address challenges related to implementing guidance from the EU's Annex 1.

Annex 1 Alignment: Addressing Contamination Control and Risk Assessment

 updated guidance on the manufacture of sterile products is imperative for industry working within the EU or servicing EU-based clients. In an interview at 

sat down with two experts in the field to discuss some of the major challenges being faced by industry in their continued effort to align with the sterile processing guidance. 

"Across the industry, what we're seeing is a lot of people are at different states for Annex I in their facilities; many have done their gap analysis, they have a timeline to compliance, and are starting to work on projects, [while] others are just starting to understand where they are in the Annex 1 world and what that really means," said Christa Myers, senior fellow and vertical market leader, Aseptic & Sterile Products at CRB Group. 

Myers noted that for many in the industry, implementing a contamination control strategy has proven complex, requiring manufacturers to take a very close look at project-related risk. That requires accessing and evaluating data, which may necessitate some companies having to retrofit or replace in order to obtain those data. 

Another challenge is standardization. "When we have these industry workshops, I think that's more of what we're looking for is, 'How do we get a site to that point, instead of kind of leaving every individual site to do it on their own, and to figure it out on their own?' And that's how we end up with so many different looks to address the same issue," Nadiyra Walker Speight, senior director, Drug Product & Finished Goods at 

, pointed out. "That's one of the mindsets that I'm looking for is that we're not all attacking this from different angles, that we're able to interpret the regulation together and actually come up with solutions together," she continued. Myers agreed, calling for a more "harmonized approach" to implementation. 

Click here for more coverage from INTERPHEX 2024

At INTERPHEX 2024, Pharmaceutical Technology sat down with Christa Myers of CRB Group and Nadiyra Walker Speight of Fujifilm Diosynth Biotechnologies to discuss implementation of Annex 1. 

Annex 1 Alignment: Addressing Contamination Control and Assessing Risk

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

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

Articles

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

Feliza Mirasol is the science editor for 

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - stock.adobe.com

Among a list of top 10 commonly seen observations during FDA inspections is the question of process validation, said Daniel Roberts, senior director of Regulatory Compliance at Sidley Austin, a global law firm, and a former FDA drug investigator. Roberts spoke in a keynote session, “FDA Regulatory Updates—Trends & Insight,” at INTERPHEX in New York City, which is being held on April 16–18, 2024.

“There [are] always [many] things to consider regarding process validation, such as making sure that your process validation is adequate and current,” Roberts said. He explained that sometimes companies with older pharmaceutical manufacturing practices get complacent with their processes, some of which were validated decades ago for a drug product that has long been on the market. However, he noted that it is important for companies to keep updated with current good manufacturing practice (CGMP) requirements.

“That is why we say the ‘C’,” Roberts emphasized, urging that companies need to take into account that their manufacturing processes must be compliant with “current” GMPs, rather than just the GMPs under which an older manufacturing process would have been validated.

“Oftentimes there will be changes in plans, and [a company’s] process validation that was done decades ago may not be reflective of [its] current processes,” Roberts said. Thus, it is important to have a process in place where it is periodically evaluated to see if it is still adequate or if it should be revised. “That is a good practice to have and, again, expectations of process validation were different in [for example] 1986 versus 2024, so just making sure that you’re current with regulatory expectations is important [for regulatory inspections].”

Another important point that Roberts made in the keynote was to emphasize the increased focus FDA has on data integrity, particularly the movement toward electronic data. “Maintaining electronic data accuracy is FDA's focus,” he said. Over time, companies are moving away from paper and more towards electronic data, and because of that, Roberts stressed that companies must have controls in place for these electronic data. However, he pointed out that data integrity still involves historical data that are on paper records.

Some of the principles of data integrity include making sure that the data are traceable back to the raw data, legible, and contemporaneously recorded. For example, Roberts said, an operator should not be weighing an item and then later recording that information based just on memory. “Making sure that things are getting recorded in a timely manner and that things are original and active kind are a big portion of this [data integrity],” he noted.

“When you submit an application to the agency, and especially when you're talking about pre approval inspections, when FDA's on site doing inspections, [the agency] wants to make sure that the data you submitted is true and accurate and right,” Roberts explained.

Former FDA drug investigator, Daniel Roberts, discusses the importance of updating process validation and maintaining proper data integrity at a keynote session during INTERPHEX.

Keynote Session Highlights Importance of Process Validation and Data Integrity (INTERPHEX 2024)

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

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.

AES Clean Technology Launches CleanLock Module

® speaks to Bill Whitford, Strategic Solutions leader at Arcadis, on the role and impact of 3D bioprinting for biologics. Whitford is a presenter on the topic of 3D bioprinting at INTERPHEX, held in New York City on April 16–18.

Whitford notes that an important aspect of 3D bioprinting is that it is one approach to 3D cell culture, which he observes is taking over cell culture in many categories. “3D culture provides many unique capabilities it's more biomimetic. Actually, there's nothing natural about growing cells in monolayer on a styrene plate, so there are many 3D culture technologies that employ many different production methods that support many categories of application and individual products,” Whitford states.

On the workflow in a 3D bioprinting facility, Whitford remarks that many complementary and supportive synergistic technologies exist that support each other. “For example,” he explains, “machine vision now is really simple. Ordering 3D printing and the ability to both direct and inspect a nascent print job using artificial intelligence (AI) … they feed on each other. The availability of bioprinters and what we call bio ‘inks’ is, in a commercial sense, what's really driving the final applications.”

“Best practices are being developed for bioprinting,” Whitford also notes, pointing out that there are many different ways of affecting bioprinting, not just with respect to the instrumentation, but with respect to the actual printing. “There is laser-effected printing; there's extrusion-effected printing. There are many different ways of getting the bio ink into the three-dimensional structure, and they all have their advantages. They all provide either a tremendous accuracy and precision or volume.”

In the interview, Whitford also discusses the future of 3D bioprinting in the cell and gene therapy sector. “The ability now—through site-directed CRISPR [clustered regularly interspaced short palindromic repeats]-type engineering—to drive the evolution of a cell towards exactly what phenotype is required is supporting the ability to … develop the bio ink … required to get the initial print job accomplished.”

At INTERPHEX, Bill Whitford, Strategic Solutions leader at Arcadis, discusses the progress made in 3D bioprinting toward commercial biologics production.

Bill Whitford of Arcadis Discusses 3D Printing for Biologics (INTERPHEX 2024)

Watson-Marlow Fluid Technology Solutions (WMFTS), a manufacturer of peristaltic pumps and associated fluid path technologies, has launched WMArchitect, a range of flexible, single-use solutions for biopharmaceutical fluid management. This platform is built on the company's predecessor product lines, such as puresu and asepticsu. The new offering aims to streamline biopharma processing, safeguard product, and reduce regulatory burden, according to an April 15, 2024 company press release.

WMFTS now offers customized designs from its component library as well as a selection of standard, ready-to-use single-use assemblies. The WMArchitect offering represents an end-to-end, single-use fluid path management solution consisting of:

Customized designs: single-use assembliescan be custom-designed to meet specific requirements with an open architecture model that allows for flexibility and compatibility with existing fluid-contact materials already used in a company’s bioprocess.

Single-use fluid transfer assemblies: these fluid-transfer assembliesare ready-to-use, are pre-designed, and offer lot traceable tubing and components for optimizing fluid transfer between equipment and process steps. The latter can be selected from a menu of validated components.

Fill/finish single-use assemblies: these fill/finish assemblies are designed tosafeguard therapeutic products during the filling process using a range of sterility-assured assembly configurations. Representative assemblies are routinely tested to determine bioburden and presence of particulates and endotoxin.

Validation testing: WMFTS specialists offer support to WMArchitectusers using bioprocessing expertise and customized validation packages. The aim is to help reduce a company’s regulatory burden.

“By listening to the evolving needs of our biopharmaceutical customers, we have created WMArchitect to provide an expert solution that supports them in mitigating their regulatory and supply chain risks,” said Nicole Hunter, head of Global WMArchitect, in a company press release. “WMFTS understands that, often, off-the-shelf products are merely a starting point. We customize our standard products to provide a complete and tested solution from a single supplier that is tailored to meet a company’s specific requirements.”

WMArchitect is suitable for high-purity biopharmaceutical process development, clinical trials, and small-to-large-scale production batches. The most critical component for maximizing performance is at the point where the tubing meets the pump, the company acknowledged in its press release. In recent years, single-use components such as tubing, connectors, and valves have allowed for more 

. For instance, single-use tubing, connectors, and valve components can eliminate cleaning-in-place (CIP) and sterilizing-in-place (SIP) procedures. Removing these steps, which are often costly, time-consuming, and contribute to downtime, can increase manufacturing throughput and productivity of a facility. Furthermore, the time and personnel once used for CIP/SIP (e.g., of stainless-steel process lines) can then be reallocated to other areas of production, thus increasing overall efficiency of the manufacturing process (1).

WMFTS’ assembly solutions are designed synergistically with the company’s peristaltic pump technologies and filling solutions to ensure reliable, repeatable performance for even sensitive processes. In addition, a dedicated WMArchitect business unit offers benefits such as reduction of validation burden, support of internal validation protocols, an open architecture approach that allows flexible integration, synergistic use with the company’s peristaltic pumps of filling systems, and supply security based on the company’s global manufacturing and supply network.

The company will be showcasing its WMArchitect single-use solutions line at INTERPHEX, held in New York City on April 16–18, 2024.

Fluid Handling Systems are Seeing Benefit from Single-Use Technologies

WMFTS has launched WMArchitect, a single-use product line that offers ready-to-use single-use assemblies and custom-designed workflows for biopharma fluid management. 

WMFTS Showcases New Single-Use Solutions Designed to Optimize Fluid Management 

Much of the current development of messenger RNA (mRNA) in the biopharma industry is focused on using mRNA-based therapeutics in the targeted treatment of cancers. Obstacles still persist, however, in the delivery method of the therapeutic. One solution lies in the formulation stage, where, for instance, lipid nanoparticle (LNP) technology has become a common mode of delivery, owing to its success in the mRNA-based COVID-19 vaccines. In an interview with Stefaan De Koker, vice-president, Technology and Innovation, etherna, 

® explores the criteria that make mRNA a good choice as a therapeutic and looks at how LNP technology is becoming a well-established vehicle for delivering mRNA. 

Evaluating the Partnership between mRNA and LNPs

Pharmaceutical Technology’s Innovations in mRNA eBook

According to De Koker, mRNA combines three significant advantages compared to other drug modalities. First, mRNA is an extremely flexible platform. For instance, mRNA sequences can be easily modulated, and, hence, they can encode virtually any therapeutic protein, “whether it’s in the cytosol of the cell, on the membrane, or even a secreted protein,” said De Koker. The ability to easily modulate mRNA sequences was on reason why mRNA was well suited to a pandemic case, such as COVID-19. It also makes mRNA well suited for developing personalized immunity, such as, a cancer vaccine. In this instance, the vaccine can be adapted to the antigen profile of a tumor.

A second major advantage of mRNA is the ease of manufacturing, says De Koker. It can be produced quickly, which, again, was exemplified by the COVID crisis, where, within a few months, mRNA vaccines were in clinical studies, he emphasizes. “They were also clearly much faster to reach approval compared to more conventional therapeutic modalities, [such as] protein-based vaccines or viral vector-based vaccines,” De Koker adds.

The reason behind mRNA’s quick synthesis is that production can be done entirely 

, and thus there is no need for cells to produce it, De Koker emphasizes. mRNA manufacture is based on an 

 transcription reaction, which uses a viral polymerase to amplify the mRNA. Moreover, De Koker explains, mRNA contains only four building blocks, which means it has constant physical and chemical properties. “Thus, regardless of the protein [one] wants to encode, [they] would have the same physical/chemical properties. This, [therefore], allows [one] to develop generic manufacturing processes,” De Koker says.

A third beneficial aspect of mRNA is the fact that the immunogenicity of the platform can be modulated. “This means that the mRNA and the formulation can either be made less (for therapeutics) or more immunogenic (for vaccines) based on the application. It really makes the immune system believe that the viral infection is ongoing, and it needs to respond to that infection by mounting a strong immune response,” De Koker explains.

“These three things together—the flexibility, the speed of manufacturing, and ability to modulate the immunogenicity of the platform—makes mRNA a versatile platform for vaccines and other uses,” De Koker states.

When referring to this article, please cite it as Mirasol, F. Evaluating the Partnership between mRNA and LNPs. 

Pharmaceutical Technology Innovations in mRNA 

The LNP success in mRNA vaccines leads to their establishment as a standard in mRNA delivery.

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - © Artur - stock.adobe.com

FDA announced on April 15, 2024 that it has established the Center for Clinical Trial Innovation (C3TI) in the Center for Drug Evaluation and Research (CDER). 

 was created in response to the need to enhance the implementation of CDER’s efforts to innovate and maximize drug development. The new center will promote activities CDER is doing to create innovation in clinical trials. These activities will include internal and external communications and collaboration.

Created as a central hub within CDER, C3TI will support approaches to clinical trials that will make drug development more efficient by sharing lessons learned across CDER’s existing initiatives in clinical trial innovation. C3TI will manage a demonstration program to expand opportunities for sponsors of trials to collaborate with CDER and spur additional implementation. This demonstration program will include point-of-care or pragmatic trials, Bayesian analyses, and trials that use selective safety data collection.

C3TI will allow internal and external parties to access information about innovation efforts, collaborate with CDER, identify resources, and identify development programs. The center will help those involved with clinical research stay current with innovations and improve the effectiveness of trials. It will also help to increase participation in clinical trials from diverse populations.

“For years, CDER has championed innovation, and our activities to foster and support innovation span drug development programs, therapeutic areas, and disciplines. These CDER efforts have led to improvements in the design and conduct of clinical trials that are intended to efficiently generate evidence on the safety and effectiveness of new therapies in ways that meet the growing demands of drug development,” the agency stated in a press release.

A public docket was opened by CDER in 2023, and a two-day public workshop was held in March 2024,in collaboration with the Duke-Margolis Institute for Health Policy, to address how drug development could be improved by innovations in clinical trial approaches. According to Kevin Bugin, PhD, lead for C3TI and deputy director of operations in the Office of New Drugs (OND), “CDER staff noted they would benefit from greater exposure to or experience with the use of innovations in their regular review work. There is a desire across the drug development ‘ecosystem’ to integrate innovation, but there is a need for more direction on how to better bridge the gap between policy and implementation” (1).

“Based on this insight, C3TI will aspire to create more opportunities for staff to participate in development programs planning to implement novel trial approaches to gain experience with a given innovation, via a C3TI Demonstration Program. C3TI will also explore how to create new opportunities for CDER staff to receive training and exposure to new clinical trial methods, technologies, and tools. Lastly, C3TI intends to better capture and disseminate lessons learned from implementing a given clinical trial innovation through improved communication and coordination with colleagues (e.g., dedicated rounds to discuss clinical trial innovation) and with external parties (e.g., public meetings or webinars),” said Bugin.

“CDER’s long-standing efforts to embed innovation in clinical trial design and conduct into our regulatory work have been crucial in bringing new therapies to areas of unmet medical need,” said Patrizia Cavazzoni, MD, director of CDER, in the press release. “We are eager to build on this foundation by launching C3TI to further spur the adoption of clinical trial innovation across industry and within CDER.”

Bugin stated that he plans for the center to accelerate innovation through collaboration and promotion of these initiatives. More information about C3TI can be found on 

FDA. CDER Launches a Center for Clinical Trial Innovation. 

https://www.fda.gov/drugs/cder-conversations/cder-launches-center-clinical-trial-innovation

FDA. CDER Center for Clinical Trial Innovation (C3TI). 

 (accessed April 15, 2024). https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/cder-center-clinical-trial-innovation-c3ti

C3TI will promote CDER’s clinical trial innovation activities both internally and externally.

FDA Establishes Center for Clinical Trial Innovation

On April 12, 2024, the European Medicines Agency announced that its Pharmacovigilance Risk Assessment Committee (PRAC) has concluded that there is no link between glucagon-like peptide-1 (GLP-1) receptor agonists and suicidal or self-harming thoughts or actions. GLP-1 receptor agonists (e.g., dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide) are used to treat type 2 diabetes; some of these medications are also authorized for weight management.

 after reports of users of liraglutide and semaglutide having thoughts of suicide and self-harm (1). PRAC requested additional data from marketing authorization holders of these types of drugs in November 2023. Results from a study published in 2024 were also analyzed by PRAC (2). The study examined the risk of suicide and self-harm in patients with type 2 diabetes. The study results did not show there to be a link between GLP-1 receptor agonists and a risk of suicide/self-harm thoughts or actions.

“After reviewing the available evidence from non-clinical studies, clinical trials, post-marketing surveillance data and the available studies the PRAC considers that no update to the product information is warranted. The marketing authorization holders for these medicines will continue to monitor these events closely, including any new publications, as part of their pharmacovigilance activities and report any new evidence on this issue in their Periodic Safety Update Reports (PSURs),” EMA stated in a press release.

between the drugs and thoughts of suicide after a preliminary evaluation. “Because the information provided was often limited and because these events can be influenced by other potential factors, we determined that the information in these reports did not demonstrate a clear relationship with the use of GLP-1 RAs. Similarly, our reviews of the clinical trials, including large outcome studies and observational studies, did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions. However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, we cannot definitively rule out that a small risk may exist; therefore, FDA is continuing to look into this issue,” FDA stated (3).

EMA’s PRAC also provided safety information to healthcare professionals regarding new Rybelsus tablets (oral semaglutide) on April 12. PRAC was asked to consult on a proposed direct healthcare professional communication (DHPC) as part of an ongoing application for new strengths of Rybelsus tablets. PRAC agreed to the content in the DHPC, and it will be forwarded to the Committee for Medicinal products for Human Use for adoption. Once finalized, the DHPC will be provided to healthcare professionals by marketing authorization holders. Rybelsus is used control blood glucose levels in adults with type 2 diabetes.

EMA Statement on Ongoing Review of GLP-1 Receptor Agonists

 Association of Semaglutide with Risk of Suicidal Ideation in a Real-World Cohort. 

FDA. Update on FDA’s Ongoing Evaluation of Reports of Suicidal Thoughts or Actions in Patients Taking a Certain Type of Medicines Approved for Type 2 Diabetes and Obesity. 

The agency’s risk assessment committee has concluded that available evidence has not been found that supports a causal association between glucagon-like peptide-1 receptor agonists and self-harming thoughts and actions.

Featured Content

Behind the Headlines Episode 27

Ask the Expert

Drug Digest September 2025

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

Top Trends Reshaping Pharma R&D