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

Feliza Mirasol is the science editor for 

On Oct. 19, 2023, Waters Corporation announced that it has launched OligoWorks solid phase extraction (SPE) Kits and components, which are meant to improve sample preparation for liquid chromatography (LC)–mass spectrometry (MS)-based bioanalytical quantitation of therapeutic oligonucleotides.

The kits are designed to deliver up to 2x higher oligonucleotide recovery from biofluids, according to a company press release. The kits’ design also delivers improved LC­MS sensitivity and reproducibility for supporting robust quantitation. Because these capabilities enable lower limits of quantitation, the kits can reduce the need for repeat experiments.

The kits also use an innovative, enzyme-enhanced, and detergent-free sample pre-treatment that, according to Waters in the press release, reduces washing steps and improves mass spectrometer compatibility. This design enables for direct injection LC–MS analysis and is also what allows for the lower limits of quantitation. The kits can also be fully automated, which can improve productivity or simply help scientists gain back time via the reduction of manual steps and oversight.

The OligoWorks SPE Kits are available immediately and complement other Waters tools, including MaxPeak Premier Columns, ACQUITY Premier LC System and Arc Premier LC System, Andrew+ Pipetting Robot. The new kits also support the sensitivity of the Waters Xevo TQ Absolute Mass Spectrometer.

" … Waters is committed to solving customer pain points and enabling greater analytical performance and productivity. Our new OligoWorks SPE Kits directly address oligonucleotide bioanalysis sample prep challenges across diverse oligo therapeutics," said Erin Chambers, vice-president, Consumables and Lab Automation, Waters Corporation. "The science and societal effects of these therapies are exploding given their ability to address human health issues. Our workflow and kits will drive an acceleration of oligo bioanalysis projects and drug development timelines; ultimately improving the experience for drug candidates."

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Waters has launched OligoWorks SPE Workflow and Kits, which is aimed at accelerating the bioanalysis of oligonucleotides.

Waters Launches New Oligonucleotide Bioanalysis Kits

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On Oct. 17, 2023, Lisata Therapeutics announced that the European Medicines Agency (EMA) granted orphan drug designation to LSTA1, Lisata’s lead product candidate for pancreatic cancer treatment. As of the publication of this article, LSTA1 has several ongoing and planned clinical studies conducted globally. These studies use a variety of solid tumor types, including pancreatic cancer, with a range of anti-cancer regimens.

LSTA1 is an investigational drug intended to aid co-administered or tethered anti-cancer drugs to more effectively penetrate solid tumors by activating a novel uptake pathway. LSTA1 activates the pathway in a tumor-specific way, potentially modifying the tumor microenvironment and making tumors more venerable to immunotherapies. There is significant non-clinical data showing LSTA1 enhancing delivery of a variety of existing and emerging anti-cancer therapies, including immunotherapies, chemotherapeutics, and RNA-based therapeutics.

The orphan drug designation is given to drugs and biologics that treat rare disease, which affect no greater than five in 10,000 people in the European Union. The designation is based on a positive opinion from the EMA Committee for Orphan Medicinal Products. The companies of eligible products receive EU marketing exclusivity for 10 years after approval, possible fee reductions, and protocol assistance from EMA.

“To date, LSTA1 has demonstrated favorable safety, tolerability, and activity to enhance delivery of standard-of-care chemotherapy for patients with metastatic pancreatic cancer,” said Kristen K. Buck, M.D., executive vice president of R&D and Chief Medical Officer of Lisata, in a press release. “Obtaining orphan drug designation from the EMA reinforces our belief that LSTA1 offers major improvement in treating patients with this terrible disease. We are excited by the promise of LSTA1 for the treatment of pancreatic cancer and other solid tumors and are committed to advancing our development programs with the goal of providing a benefit to patients.”

The designation will grant Lisata EU marketing exclusivity for 10 years after approval and protocol assistance from EMA.

Lisata Therapeutics Announces EMA LSTA1 Orphan Drug Designation for Pancreatic Cancer Treatment

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Royalty Pharma announced on Oct. 19, 2023 that it has signed an agreement with PTC Therapeutics to acquire additional royalties on Roche’s Evrysdi. Royalty will pay $1.5 billion upfront, with the possibility of purchasing the remaining royalties for up to $500 million at a later date. Evrysdi, which is marketed by Roche, is an “orally administered survival motor neuron-2 (SMN2) splicing modifier for the treatment of spinal muscular atrophy [SMA].” It received FDA approval in 2020 and has since treated more than 11,000 patients internationally. In 2022, Evrysdi generated approximately $1.2 billion in sales, 87% higher than in 2021.

As of the publication of this article, Roche’s royalty payment on Evrysdi is tiered, ranging from 8% to 16%. Following this transaction, Royalty Pharma’s ownership of the Evrysdi royalty is increasing from 43% to 81%. Until Dec. 31, 2025, PTC will have the option to sell its remaining Evrysdi royalties to Royalty Pharma for $500 million in five equal tranches. If PTC uses less than three of these options, Royalty Pharma will have the opportunity until March 31, 2026 to purchase 50% of the remaining royalties for $250 million.

“We are excited to acquire an additional royalty interest in Evrysdi, a convenient, oral therapy that has transformed the lives of SMA patients worldwide,” said Pablo Legorreta, founder and chief executive officer of Royalty Pharma in a Royalty Pharma press release. “This is our second transaction with PTC, which builds on our longstanding partnership, and highlights our ability to structure creative, win-win funding solutions for our partners. Further, our unmatched scale and deep knowledge of SMA positioned us to provide PTC with substantial capital in a timely fashion, another unique aspect of our business model. This transaction is expected to further enhance Royalty Pharma’s long-term growth and diversification. We remain incredibly excited for our future given our robust transaction pipeline.”

The spinal muscular atrophy treatment, currently marketed by Roche, generated $1.2 billion in sales in 2022.

Royalty Pharma to Purchase up to $1.5 Billion of PTC Therapeutics’ Royalty on Roche’s Evrysdi

The trend toward digital transformation in biopharmaceutical manufacturing continues as advanced technologies enter the scene and work their way through to manufacturing operations. With the availability of technologies to take automated biomanufacturing from preclinical to commercial-scale, the industry may start to see a wave of changeovers from manual processes to an automated, digital environment. This episode of the 

Podcast will discuss the realities of switching over from manual to digital, and what to expect.

Ajit Yeole, senior director, Life Sciences Manufacturing, Cognizant

Ajit Yeole is the senior director for Life Sciences Manufacturing at Cognizant, based in London, UK.He is responsible for strategy, smart manufacturing, developing new service offerings, and digital accelerators targeted towards addressing the industry needs. Has been closely working on engagements around manufacturing and quality involving emerging technologies (Industrial IoT, advanced analytics, AR/VR , and others) using agile and design-thinking-led approaches. He has led the manufacturing operations management practice for Cognizant in Europe and has delivered large manufacturing programs while collaboratively building tools and templates for consulting offerings. Previously, he worked in manufacturing operations management, IoT (M2M) and OT/ industrial automation as a consultant, solutions architect, and business unit head.

Laks Pernenkil, principal and practice leader, US Life Sciences Product & Supply Operations, Deloitte

Laks Pernenkil, PhD, is a principal in Deloitte’s Life Sciences Product, Supply, Manufacturing and Quality Operations practice based in McLean, Va. He has more than 15 years of consulting and technical operations experience in pharmaceutical, biologics and medical device sectors. At Deloitte, his experience includes smart/digital manufacturing and plant floor operations, plant engineering, facilities management, material sourcing, distribution, performance improvement, operational excellence, and market entry operations strategy.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

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In this episode of the Drug Solutions Podcast, industry experts discuss the challenges and advantages of the digitalization trend in the biopharma industry, with particular emphasis on the impacts to biomanufacturing.

Drug Solutions Podcast: Digital Transformation in the Biopharma Industry

On Oct. 18, 2023, SCHOTT announced that it has launched a new component for biopharmaceutical process analysis, the ViewCell flow cell. The purpose of this new component is to optimize downstream processes in the biopharmaceutical industry by enabling safe, continuous process control directly in the production line.

The introduction of the ViewCell flow cell follows the company’s launch of its ViewPort sensor port for bioreactors. Through a sterile-safe optical window, the flow cell allows for 

 measurements of biological and physical parameters in downstream processing. The flow cell can be used during purification and filtration as well as during subsequent formulation. This capability thus reduces the need for both physical sampling and storage tanks, according to a company press release.

According to the press release, optical sensors or spectrometers are connected to the flow cell for monitoring, which means that the measuring instruments do not come into contact with the medium, and thus do not penetrate the sterile barrier. This allows for the sensors or spectrometers to be easily replaced during ongoing production, which the company states in its press release is a major advancement compared to fixed probes. In addition, a glass-to-metal connection allows for a sterile-safe design, which also increases the safety and efficiency of process analysis, contributing to an overall optimized yield.

The company stated in the press release that ViewCell allows biomanufacturers to quickly build and test small-scale flow systems for Raman analysis, which are used to mimic real-world industrial processes. The compact design of the device reduces the overall volume of sample material required, which cuts down on waste and costs—key considerations in the handling of expensive or difficult-to-obtain test materials.

SCHOTT now offers ViewCell, a new component meant to add flexibility to biopharmaceutical process control.

SCHOTT Launches ViewCell Flow Cell for Biopharma Process Control

Key highlights from the CPHI Pharma Survey were announced as of Oct. 13, 2023, and the full findings will be published at CPHI Barcelona as part of the CPHI Annual Report. These results will provide insights from more than 250 global pharma executives, including discoveries such as pharma confidence dipping below the record scores of 2022, although it has remained extremely resilient despite wider macro uncertainly, according to the press release.

Further, the CPHI Pharma Index reported its second highest ever total, which was 2.5% down on the 2022 all-time high. These results highlight the medium-term trajectory of the industry and the strength of market fundamentals. The United States remained the top overall ranked nation, with India also continuing to make year-on-year inroads for significant growth in 2024. India did, however, remain at the top of the “growth” category for the second year in a row, scoring 7.8 out of 10. It also saw improvements in the score for “biologics quality” and finished behind the United States for “overall competitiveness”. According to the report, India is predicted to undergo a fast transformation from a generics hub to an innovation-focused pharma economy, driven by the incremental steps of large contract development and manufacturing organizations.

One of the more startling discoveries, according to the press release, is that the report predicts that an “India plus one” strategy will be adopted in the next five years. “When you look collectively at the data points in the Annual Survey, you see that after a reset from record scores in 2022—when many reported record profits—the industry is now well positioned for growth in 2024,” said Tara Dougal, Content Director–Pharma, in a press release.

The report also identified that many of the industry’s growth drivers that were seen in 2019 are still present but are now supplemented by the breakthroughs in microbiome therapeutics, while artificial intelligence now looks like the next efficiency used in the industry over the next five years.

“Our analysts predict outsourcing will continue its growth trajectory in 2024 and beyond—which is obviously a tremendously positive message for the industry as we approach CPHI Barcelona,” Dougal said in the press release. “It is also why we have ensured that ‘outsourcing strategies’ are a central theme of this year’s content, and the overall takeaway is of quiet and confident optimism. In fact, this will remain an ongoing theme for CPHI content, helping our audience to meet their objectives around partnering and supplier selection year-round.”

These results will provide insights from more than 250 global pharma executives, including discoveries such as pharma confidence dipping below the record scores of 2022, although it has remained extremely resilient despite wider macro uncertainly, according to the press release.

CPHI Annual Survey Finds Global Pharma Resilient with India the Chief Beneficiary of Macro Changes

On Oct. 17, 2023, SpliceBio, a genetic medicines company headquartered in Spain, announced that it has signed an exclusive collaboration and licensing agreement with Spark Therapeutics under which SpliceBio will use its proprietary protein splicing platform to develop a gene therapy for treating an inherited retinal disease. Details about the disease target were not disclosed.

Under the agreement, both companies will conduct a research collaboration utilizing SpliceBio’s technology platform. The protein splicing platform offers the potential to address diseases that currently cannot be treated with gene therapies. In those cases, the gene required for the treatment is too large to be delivered by adeno-associated virus (AAV) vectors. With this agreement, Spark will have exclusive worldwide rights to develop, manufacture, and commercialize a gene therapy resulting from this research collaboration; the gene therapy will target an undisclosed inherited retinal disease, according to a company press release. The agreement makes SpliceBio eligible to receive upfront, opt-in, and milestone payments of up to $216 million as well as royalties on net sales.

“This research collaboration and license agreement is an exciting opportunity to develop a novel gene therapy in an area of high unmet medical need. We are proud that Spark Therapeutics recognizes the potential of our pioneering [p]rotein [s]plicing platform and the profound impact it could have in the treatment of inherited retinal diseases that are unable to be effectively addressed by other gene therapy approaches,” said Miquel Vila-Perelló, CEO and co-founder of SpliceBio, in the press release. “In addition to the Spark collaboration, we continue to develop our lead program in Stargardt disease and further build our capabilities and pipeline of wholly owned gene therapy programs to develop life-changing therapies for patients in need.”

“This partnership builds on Spark’s leadership in gene therapies for inherited retinal diseases. Our breakthrough gene therapy LUXTURNA [voretigene neparvovec-rzyl] demonstrated how we can change the lives of patients with biallelic mutations in the RPE65 gene whose physicians have determined their eligibility for treatment. At the same time, there are many more people with other inherited retinal diseases that need treatment options,” said Federico Mingozzi, chief science and technology officer of Spark Therapeutics, in the release. “With our complementary capabilities, combined deep technical knowledge, and SpliceBio’s impressive protein splicing platform we hope to make further progress in the treatment of inherited retinal diseases, bringing new gene therapies into the clinic and to commercial availability.”

Spark Therapeutics and SpliceBio have formed a collaboration to develop a gene therapy that can treat an inherited retinal disease.

Spark Therapeutics Partners with SpliceBio on a Gene Therapy for Eye Disease

Kent Malmros is senior director of training at Veeva Systems. He has spent the majority of his career delivering technology-enabled training solutions to life-sciences companies and has held leadership positions at companies that include AdMed, ClearPoint (Red Nucleus), and UL EduNeering (UL).

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The number one reason biopharma companies receive a warning letter from FDA is not having procedures in writing or fully followed signaling an opportunity to improve employee training practices (1). The training matrix can be the unsung hero of a well-defined good practices (GxP) training program because it ensures the accountability and traceability required by regulators.

Every company tries to deliver effective training by getting the right content to the right people at the right time to ensure qualification, job readiness, and professional development. Establishing a GxP training matrix and a strategic plan can help, but without a single programmatic approach to building a matrix, many tend to lean on traditional processes that haven't worked well in the past.

Industry leaders at the forefront of improving learning outcomes have shared insights on why every company can benefit from developing a training matrix and best practices to get started.

The training matrix and training plan are interdependent, each feeding off the other to support employees and ensure they can meet all requirements. Understanding the role each play is critical to developing a comprehensive and compliant learning program.

Training matrices include a collection of all the curricula that employees need to complete for qualification to perform a job. The training plan defines the order in which courses should be taken, how they will be delivered, and key deadlines for completion.

"A training matrix provides the overarching strategy for what a particular group or organization needs to do to qualify an employee," said Christian Torstensson, director of learning and development at Sanofi. "The plan details how to execute that matrix" (2).

Developing a training matrix should be a priority for all companies, large or small. Unfortunately, a frequent practice across the industry is putting all existing training plans into a learning management system (LMS) and using it as the default matrix. This approach provides a quick fix but can increase risk when deployed without a defined strategy.

To address this challenge, thoughtful strategies around how the different training plans work together should be created. Additionally, looking at the plans holistically can help drive efficient qualifications practices and lower the risk of non-compliance.

Understanding regulations to streamline employee education

A poll of training and employee development executives found that 93% take a role-based approach to building curricula (2). While role-based training can provide a solid blueprint to cover all education needed for core compliance, it may not give organizations the best path toward extended qualifications and personal development of employees.

) Title 21, "each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience" to enable them to do their job (3). With such broad guidance on training, companies adopt numerous strategies to drive job requirements and prove completion.

"The regulations don't provide details about how companies need to conduct qualification," said John Constantine, senior vice president at Orchestrall. "Pick the right matrix or method that fits best within the organization to ensure inspectors can confirm the company has done what is in its documentation. Stick with your matrix, and don't deviate from it" (2).

A usual pitfall is designing an overly complex matrix to meet regulatory requirements. Increased complexity leads to processes that are hard to track and data that are not unified. FDA's guidance is simple, so push that through to your strategy. A simple matrix incorporating governance and adherence is an excellent approach to apply.

To assemble a matrix, it is imperative to develop a logical hierarchy and structure driven by individuals involved in learning and development. The business function should own what an employee needs to be trained on, and the training department handles the execution.

"It is imperative to have a good solid structure and management within the individual departments that ensure that people are trained on what they need," said Nicole Donovan, former director of organizational development at TOLMAR (2).

Next, identify buckets for training and define them. This step could include qualification, role, or skills-based training. Defining buckets helps people understand why they received a request to complete a training assignment. Ensure they don't overlap and make it easy for staff to choose the required courses by answering simple questions.

"Figure out what those buckets are and make it so people can answer simple questions like, are you based at this site? Are you in a GMP role? Do you work in a cleaning space?" adds Torstensson. "Those employees will be much more successful getting assignments completed."

Taking this approach defines what you need on the most basic level. Be flexible with the framework to determine what works and what doesn't. Talking to individuals can provide a deeper understanding of their job requirements and how those fit with FDA guidance. Ultimately, the process helps learning teams match individuals, teams, and departments with the training they need to perform and ensure qualification and competency.

Establishing real-time visibility with a digital approach

A digital learning management system (LMS) can help provide process rigor by allowing team leaders to tag training by location, site, department, and facility while adding recurrences based on requirements. This helps to bring together data all in one place, making it easier to analyze information, identify patterns or missing assignments, and prove compliance.

"Many companies try to fit the old way of doing things into their digital LMS, which is not the right way to go," says Constantine. "The path forward is to take the best of how things are done now, with a training matrix, and adapting it to what the system is best at doing."

When evaluating an LMS, look for solutions that offer:

assignment mapping based on industry, job functions, departments, or roles

automatically triggered training tasks based on events such as approved content changes and CAPA plans.

"With a digital system, we know when people are completing training on time, if they are late, or not completing it at all," adds Donovan. "These are big milestones we need to know to improve our processes and ensure staff are qualified to perform their jobs. A digital system helps eliminate all the unknowns of using paper."

Companies that can build a training matrix and an execution plan are on the fast track to ensure audit readiness. Establishing common terminology and understanding the relationships across definitions, processes, systems, and delivery are key. Keeping each aspect simple helps make it understandable and implementable in the long term.

At times, training leaders are battling each other instead of helping. Not intentionally, but just because they're trying to execute every day without context. A training matrix can provide alignment across leadership, departments, line managers, and employees, delivering clarity and accountability.

Companies can remain a step ahead by establishing a strong GxP training matrix and pairing it with a strategic plan and LMS. But all three support each other. No one alone can transform training operations, as Torstensson pointed out. "When organizing training to see trends and consistency, the LMS shouldn't drive the process. Far too often, a system is selected because, in some way, the thought is it will magically make the training program into something that it isn't," he said (2).

Best Practices for Developing and Maintaining a GxP Training Matrix

Kent Malmros is vice president of training strategy at Veeva. He has spent most of his career delivering technology-enabled training solutions to life sciences companies and has held leadership positions at AdMed, ClearPoint (Red Nucleus), and UL EduNeering (UL).

Companies can benefit from developing a single programmatic approach to a GxP training matrix.

Quality's Unsung Hero: The GxP Training Matrix

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On Oct. 18, 2023, the European Medicines Agency (EMA) announced that national competent authorities have notified the agency that pre-filled pens falsely labeled as Ozempic (semaglutide, 1 mg, solution for injection) have been found at wholesalers in the European Union (EU) and the United Kingdom. EMA stated in a press release that these reports of fake Ozempic follow an increase in demand for the diabetes medication, which has also created a shortage of the drug.

The pens’ labels are in German and originated in Austria and Germany. The falsified pens include genuine information from Ozempic packs including batch numbers, 2D barcodes, and unique serial numbers. According to EMA, the serial numbers came up as inactive when they were scanned. The falsified pens also differ in appearance from the genuine pens. A photo of the falsified pen can be found on the 

Regulators in the EU and police are investigating the falsified pens, and wholesalers and pharmacies have been warned of “suspicious offers of Ozempic.” German and Austrian regulators have issued statements of non-compliance with good distribution practices to wholesalers. It is recommended that wholesalers and pharmacies use caution with purchasing Ozempic from supplier and that packages be checked in the verification system.

EMA is advising patients to check the patient information leaflet that comes with the medication to be sure the pen looks correct. If they suspect the pen is fake, they should not use the medication and return the product to the pharmacy. However, the agency reports that there is no evidence that the falsified products have been given to patients from legal pharmacies.

The agency is monitoring the situation and will provide updates as they are available.

The agency is warning patients and healthcare providers about pre-filled pens falsely labeled as Ozempic.

EMA Warns About Falsified Ozempic Pens

Forge Biologics (Forge), a US-based contract development and manufacturing organization (CDMO), announced on Oct. 11, 2023 that it has joined the California Institute for Regenerative Medicine’s (CIRM’s) Industry Resource Partner Program under which Forge will manufacture adeno-associated adenovirus (AAV) vectors to help advance gene therapy programs in California. The state of California is providing $5.5 billion in funding, according to the company press release.

Under the partnership, Forge will offer assistance to CIRM’s partners, which include industry and academic investigators, to accelerate gene therapy development and manufacturing. As a result of the assistance provided by Forge, it is expected that CIRM’s programs will run more efficiently and accelerate progression through clinical phases of development to commercialization.

Forge focuses on accelerating AAV gene therapy programs at any stage, from preclinical to clinical and commercial manufacturing. All manufacturing is done at Forge’s 200,000-ft2 current good manufacturing practice facility in Columbus, Ohio.

“We are enthusiastic about collaborating with the California Institute for Regenerative Medicine to help advance gene therapy programs through our clinically proven manufacturing processes, which may help CIRM programs more quickly reach clinical trials in a state fulfilling the promise of gene therapy to help patients in need,” said Timothy J. Miller, CEO, president, and co-founder of Forge, in the press release.

“CIRM’s Industry Resource Partner Program aims to create a force-multiplier effect by bringing in industry partners who possess resources, experience, and expertise to accelerate CIRM-funded regenerative medicine research projects,” said Shyam Patel, senior director of Business Development and Alliance Management at CIRM, in the release. “By agreeing to provide access to its AAV manufacturing services, Forge Biologics joins our collaborative network of partners who share our unwavering commitment to advancing transformative regenerative medicine therapies for patients.”

The California Institute for Regenerative Medicine has partnered with Forge Biologics, which will manufacture AAVs to help accelerate gene therapy programs in California.

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