Aligning mRNA Progress with Regulatory Streamlining

BioPharm Peer Exchange

Dosage Forms: Roundtable on Oral Solid Dosage Trends

Drug Solutions Podcast: 

Pharmaceutical packaging must advance to adapt to new, complex modalities

Out-of-the-Box Packaging Advancements

From Theory to Reality: Automating Process Development

Drug Digest: 

The Importance of Appropriate Supplier Oversight

Ask the Expert

Richard K. Burdick is principal of Burdick Statistical Consulting and Professor Emeritus of Statistics at Arizona State University.

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To assess the impact of process changes, stability data (e.g., measurements of drug product over time) at recommended storage conditions are often required. Pre- and post-change degradation rates (slope over time) do not need to be identical, but do need to be highly similar, with scientific justification that any observed differences will not impact safety or efficacy. Because slopes at the recommended storage conditions are often quite small, the product is also exposed to non-recommended storage conditions (e.g., higher temperature) to quickly accelerate degradation. In comparability studies, it is necessary to demonstrate that the degradation rates (slopes) of the pre-change and post-change processes are comparable. Burdick and Sidor proposed a statistical test of equivalence that can be applied in these situations (1). However, it might be the case that practically sized experiments may lack sufficient power to perform the equivalence test. An alternative approach is proposed based on the quality range test recommended by FDA in their draft guidance for comparing biosimilars (2). This approach uses a visual interpretation of study results based on a heuristic rule for claiming process comparability.

A typical study design used in an accelerated experiment requires L=3 lots from both the pre-change and post-change processes. There are typically T=3 time points measured on each of the six lots with one measurement per lot at each time point. 

 displays plots of two data sets with L=3 lots, T=3 time points (

=28 days), and one measurement at each time point (a total of nine values for each process). The response variable is cation exchange (CEX) Main (%). The lines shown in the figure are the least square lines of fit for each of the six lots. The complete data set is provided in 

Of particular interest is the comparison of the line slopes for the two processes. Slopes differ within each process due to analytical error. Differences between processes indicate a difference in degradation rate between the two processes and should be investigated for impact on safety or efficacy.

A visual representation that allows one to focus exclusively on slopes is provided in 

. Here suitable constants have been added to each y-intercept so that they are all equal to the same (arbitrary) value.

 that the slopes from the two processes in Data Set 1 overlap the same region and there is no clear delineation between the two processes. In contrast, all three slopes of the post-change process are steeper than those of the pre-change process in Data Set 2, and there is no overlap. One might declare comparability in Data Set 1; whereas with Data Set 2, it appears the processes may not be comparable.

The quality range test provides a statistical heuristic based on a visual comparison of the slope values of the pre-change and post-change lots. The quality range test was introduced by FDA in their 2019 guidance document for analytical comparison of biosimilar products (2). One can perform the quality range test for the accelerated study by following these steps:

®
Vol. 48, No. 10
December 2024
Pages: 26–28

When referring this article, please cite it as Burdick, R. K. Comparability in Accelerated or Stressed Stability Studies Using a Quality Range. 

Articles

A statistical procedure based on a quality range is proposed for demonstrating comparability between pre-change and post-change process slopes in an accelerated or stressed stability study. 

Comparability in Accelerated or Stressed Stability Studies Using a Quality Range

Feliza Mirasol is the science editor for 

Cambrex, a contract development and manufacturing organization, announced on Dec. 5, 2024 that it has entered into an agreement with Eli Lilly and Company (Lilly) aimed at Cambrex providing accelerated access to clinical development capabilities for Lilly's biotech collaborators.

Under the agreement, Cambrex will partner with Lilly's early external innovation and collaboration arm, Lilly Catalyze360-ExploR&D. Cambrex will provide drug substance, drug product, analytical service labs, and R&D expertise to biotech collaborators teamed with Lilly Catalyze360.

"We are excited to support Lilly's mission to enable external biotech collaborators to expedite their product development," said Brandon Fincher, president of Early Stage Development & Testing at Cambrex, in a company press release (1). "Our Longmont [Colorado] facility offers all services required to advance early stage small molecules into the clinic with speed, flexibility, and scientific excellence. We look forward to propelling Lilly Cataylze360 collaborators forward on an efficient path to success with their products."

Lilly Catalyze360 focuses on advancing science and supporting emerging medicines via investment and through its three pillars—Lilly Ventures, Lilly Gateway Labs, and Lilly ExploR&D. Under the agreement, Cambrex will partner with ExploR&D, which brings enterprise learning, scientific know-how, and best-in-class research and development capabilities to accelerate partner science, according to the company press release.

Primary services offered through the agreement will be conducted in the Longmont, Colo., facility. Additional support will be provided by Cambrex's network, as needed. Cambrex's Longmont facility specializes in the early development of investigational new drugs, from process development and drug substance manufacturing through to formulation development and drug product manufacturing. The facility houses capacity for non-good manufacturing practice (GMP) and current good manufacturing practice (CGMP) production. The site simultaneously provides full analytical development and CGMP testing support.

Cambrex also recently strengthened its process development capabilities when it formed a strategic collaboration with Atinary Technologies in September 2024 (2). Under this collaboration, Snapdragon Chemistry, a Cambrex company, will integrate Atinary’s AI-driven and automated process optimization technology with its own state-of-the-art laboratories and process development capabilities, which will allow Snapdragon to tackle complex challenges in drug development. Snapdragon specializes in API process development, with a focus on continuous flow process development, lab automation, and complex synthetic APIs.

Under the collaboration with Atinary, Snapdragon has integrated its proprietary LabOS software platform with Atinary’s SDLabs platform to build a fully automated and AI-driven, medium-throughput Solid-Phase Oligonucleotide Synthesizer (SPOS). The purpose of the SPOS is to enable autonomous multi-objective process optimizations. Atinary’s AI platform has enhanced Snapdragon’s process optimization campaign with significant improvements across tested applications. Snapdragon was able to demonstrate up to an 18% increase in product yield and a 22% reduction in cost compared to processes previously optimized by an experienced scientist (2).

“Atinary is committed to accelerating innovation and delivering cutting-edge solutions to our customers,” said Hermann Tribukait, PhD, co-founder and CEO of Atinary Technologies, in a company press release issued in September (2). “Our work with Snapdragon showcases the power of our AI and data-driven process to solve complex chemistry and molecular discovery challenges in the pharmaceutical and biotech industry, orders of magnitude faster than traditional methods.”

1. Cambrex. Cambrex Announces Strategic Agreement with Lilly to Support Biotech Collaborator Manufacturing. Press Release. Dec. 5, 2024.
2. Cambrex. Atinary Technologies Announces Strategic Collaboration with Snapdragon Chemistry, a Cambrex Company. Press Release. Sept. 26, 2024.to Support Biotech Collaborator Manufacturing. Press Release. Dec. 5, 2024.
2. Cambrex. Atinary Technologies Announces Strategic Collaboration with Snapdragon Chemistry, a Cambrex Company. Press Release. Sept. 26, 2024.

Through the agreement, Cambrex will provide accelerated access to clinical development capabilities to Lilly’s biotech collaborators.

Cambrex Enters Agreement with Lilly to Support Biotech Collaborator Manufacturing 

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

In this exclusive Drug Digest video interview an industry expert discusses key trends impacting solid dosage drug development and manufacturing. 

Focusing on Solid Dosage Trends and Demand

In this exclusive Drug Digest video interview, Felicity Thomas, Associate Editorial Director, 

Group, interviews Dr. Ali Rajabi-Siahboomi from Colorcon about solid dosage drug development and manufacturing. During the discussion, Dr. Ali will provide an overview of the solid dosage drug development and manufacturing sector, factors driving growth in the market, challenges facing companies and the shifts in demand, the evolution of coating design, and regulatory considerations impacting oral solid dosage development and manufacturing.

Ali Rajabi-Siahboomi is the vice president and chief innovation officer at Colorcon, based at the Global Headquarter, USA. Rajabi-Siahboomi has held various academic positions in Nottingham and Liverpool JM Universities in the UK before joining Colorcon as technical director, responsible for Europe, the Middle East, and Africa in 2000. His main research interests are solid dosage form pharmaceutics, pharmaceutical technology with emphasis on oral drug delivery systems, solubility enhancement to improve bioavailability, and consistency of drugs and bioequivalence formulations. He has published more than 300 articles, book chapters, abstracts, and patents and obtained his B.Pharm. and PhD in pharmacy from the University of Nottingham (UK).

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

® editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

 Emerging Therapies and Targeted Delivery

 Advances in Small-Molecule Manufacturing

Videos

Drug Digest: Focusing on Solid Dosage Trends and Demand

Close-up of a microscope lens examining microarray slides, a crucial tool in genomic research and medical diagnostics | Image Credit: © Varunee - Stock.Adobe.com

It is well-known that developing a drug from the discovery through to commercialization is a costly endeavor, with market analysis showing that the average R&D cost to develop an asset for 2022–2023 was $2.3 billion (1). However, many drugs do not make it through to commercialization, in fact it has been reported that clinical attrition rates for drugs that have reached Phase I trials is as high as 90% of drug candidates (2).

As a result of the high costs and level of risk inherent with drug development, it is imperative that companies efficiently determine the safety and efficacy of their candidates, to minimize any potential failure. “Bioanalytical testing is essential in drug development because it ensures the safety, efficacy, and quality of pharmaceutical compounds through quantitative analysis of drugs and their metabolites in various biological matrices such as plasma, urine, blood tissue, [and so on],” asserts Sujata (Suzzy) Bhavekar, study director at SGS North America. “Early identification of side effects through rigorous testing can reduce development costs by up to 20% (3). Drugs with robust bioanalytical data are 50% more likely to gain regulatory approval (4).”

“Bioanalytical testing covers a range of techniques and technologies used to quantify drugs and their metabolites, or biomarkers, in biological media,” adds Iain Love, director, Chromatographic Bioanalysis & Discovery Sciences, Department of Chromatographic Bioanalysis, Charles River. “The concentration data generated through bioanalytical testing are important as they inform researchers on how long a drug stays in the body and the beneficial effects or otherwise while it’s in there. Knowing the concentration of drug candidates and understanding the levels at which the drug has positive or negative effects on the body is critical to drug development.”

Vital data on drug absorption, distribution, metabolism, and excretion can be gained through bioanalytical studies, which helps developers to determine dosing regimens, agrees Bhavekar. “Poor pharmacokinetics contribute to 30% of drug failures, highlighting the importance of accurate testing (5),” she says.

Additionally, bioanalytical studies help with biomarker discovery, which improves the success rate of targeted therapies by 25% and supports personalized medicines (6), Bhavekar continues. Furthermore, suitable bioanalytical testing helps ensure compliance with regulatory standards, including good laboratory practice (GLP) and good clinical practice (GCP). “Approximately 85% of drug applications meet approval criteria with solid bioanalytical data (7),” Bhavekar says.

“Regulatory considerations are extremely vital in bioanalytical studies to ensure compliance with international standards and facilitate successful drug approval,” continues Bhavekar. “Adhering to GLPs and GCPs is essential to ensure data accuracy, reliability, and reproducibility.”

“Bioanalytical testing is carried out according to strict inter(national) guidelines and quality management systems,” agrees Love. “Monitoring authorities translate globally recognized quality management systems into national regulations.”

At the national level, there are guidelines such as FDA’s guidance documents on bioanalytical method validation and immunogenicity (7,8) and the European Medicines Agency’s guidance on bioanalytical method validation (9), Bhakevar adds. “Compliance with 21 CFR [Code of Federal Regulations] Part 11 (10) is crucial for maintaining the credibility of electronic records and ensuring data integrity,” she says.

“In addition to these national regulations, bioanalytical studies are also carried out following the International Council for Harmonisation (ICH) M10 guideline,” confirms Love. In fact, EMA’s guidance on bioanalytical testing has been superseded by the ICH guidance (11), since its publication in 2022.

“The ICH M10 guideline provides a harmonized approach across various regions including the US [United States], EU [European Union], Japan, and other member countries [and] provides a robust framework for validating methods, focusing on precision, accuracy, selectivity, sensitivity, and reproducibility, thus enhancing global consistency in bioanalytical testing,” Bhakevar specifies. “These regulatory frameworks, including ICH M10 and FDA guidelines, form the backbone of robust bioanalytical testing, driving drug development toward clinical and commercial success.”

“Outsourcing partners are an increasingly important piece of the drug development puzzle,” notes Love. “Partnership with a bioanalytical provider can bring about several tangible advantages that can help get drugs to the patients who need them in the shortest time possible. This could be from simple access to appropriate analytical platforms to receiving advice on planning the development program.”

In terms of regulatory compliance, the right partnership with a contract research organization that complies with global regulatory standards can ensure that the bioanalytical data generated meets the relevant requirements, Bhakavar explains. “Comprehensive services [provided by a partner company], including method development, validation, and routine analysis, allow sponsor companies to focus on core R&D activities while relying on their outsourcing partner for specialized testing,” she says.

“Outsourcing partners are also likely to be able to apply experience gathered from across a broad portfolio of modalities and development scenarios that can inform program decision-making,” confirms Love. “More than ever, bioanalytical science is involved in shaping programs, so careful selection of an expert outsourcing partner is an activity that can bring about the significant benefits involved with an accelerated drug development program.”

There are also benefits in terms of the flexibility and scalability of operations that a partner company can provide for a sponsor’s needs, Bhavekar remarks. “Outsourcing provides flexibility in scaling bioanalytical operations according to project needs, from preclinical to late-stage clinical trials. This scalability helps manage resources efficiently and reduces the burden on in-house teams,” she says. “[Additionally], with large-scale facilities and automated processes, outsourcing partners can handle high volumes of samples, ensuring rapid data delivery and accelerating the drug development timeline.”

“[Furthermore], outsourcing partners invest in cutting-edge technologies and platforms, such as mass spectrometry and immunoassays, to deliver precise and reliable data, which may not be feasible for smaller companies to implement internally,” specifies Bhavekar. “Overall, outsourcing bioanalytical testing to a reputable partner can enhance the efficiency and quality of the drug development process, enabling sponsor companies to achieve their project goals more effectively.”

“There has never been a more vibrant time to be involved in bioanalytical testing. It’s sometimes a challenge to keep up with the innovation both from within the drug development industry and from supporting partners,” notes Love. “There have been, and continue to be, some hugely innovative therapies discovered and developed by the pharma and biotech sectors. At the same time, instrument and software manufacturers continue to push boundaries with what can be done to generate extremely powerful data in support of drug development.”

An area of great interest for Love is that of patient centric sampling (PSC), which is “the description given to a number of techniques and approaches that affords patients choice: choice on how a biosample is taken but also the choice of whether to provide biosamples in a clinical setting or remote from a clinical setting,” he says. “This enablement of decentralized trials is potentially the biggest and most impactful paradigm change in the clinical space for a long time.”

For Bhavekar, the many advancements that have been seen in the field of bioanalytical testing have helped to greatly improve the analysis of both small and large molecules in drug development. For example, she highlights the hybrid approach of combining ligand-binding assays with liquid chromatography coupled with tandem mass spectroscopy as a way of improving sensitivity and specificity of bioanalytical studies for both small and large molecules.

Platform approaches represent another advancement in the field, Bhavekar continues. “Enzyme-linked immunosorbent assay, plasmon resonance immunoassay, hybridization assay, immuno-PCR [polymerase chain reaction] assay, and the Meso Scale Discovery platform are widely utilized methodologies,” she says. “These platforms are highly specific and sufficiently sensitive, enabling the generation of controlled and customized data that meets regulatory compliance standards.”

Other advancements include chromatographic-based techniques for greater analysis of samples, circular dichroism and differential scanning colorimetry for the assessment of stability and structural changes in large molecules, electrophoresis to help with the separation of proteins and large-molecule characterization, and multiplex immunoassays to gain insights into complex biological samples, Bhavekar notes.

“The bioanalytical field is continuously evolving, with ongoing research into novel biomarkers, advanced detection methods, and personalized medicine approaches. Staying at the forefront of these innovations is crucial for maintaining a competitive edge in the industry,” concludes Bhavekar. “By focusing on [more than just the core] aspects, sponsor companies can leverage bioanalytical testing not just as a regulatory requirement but as a strategic tool for advancing drug development and achieving market success.”

1. May, E.; Taylor, K.; Gupta, L.; Miranda, W. 

Unleash AI’s Potential: Measuring the Return from Pharmaceutical Innovation—14th Edition

. Annual Report, Deloitte, April 2024.
2. Sun, D.; Gao, W.; Hu, H.; Zhou, S. Why 90% of Clinical Drug Development Fails and How to Improve it? 

 12 (7) 3049–3062.
3. Smith, J. and Doe, A. The Impact of Early-Phase Clinical Testing on Drug Development Costs. 

Pharmaceutical Development and Technology

 24(3), 225-233.
4. FDA. Drug Approval Statistics. 2022 Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases.
5. Anderson, J. and Smith, R. Impact of Pharmacokinetics on Drug Development. 

Journal of Pharmacokinetics and Pharmacodynamics

, 48(2), 123-130.
6. Johnson, R. and Lee, K. Biomarker Discovery and Its Role in Targeted Therapy. 

. Guidance for Industry, May 2018.
8. FDA. 

Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection

. Guidance for Industry, January 2019.
9. EMA. EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2** 

Guideline on Bioanalytical Method Validation

 Title 21, 11 (Government Printing Office, Washington, DC) 241–246.
11. ICH. M10 

Bioanalytical Method Validation and Study Sample Analysis

Felicity Thomas is the Associate Editorial Director for Pharmaceutical Technology Group.


Vol. 48, No. 12
December 2024
Pages: 30–32

When referring to this article, please cite it as Thomas, F. 
Leveraging Advancements in Bioanalytical Testing. 

As the field of bioanalytical testing evolves, it is important for drug developers to stay at the forefront of the advancements to ensure they remain competitive.

Leveraging Advancements in Bioanalytical Testing

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

The European Medicines Agency (EMA) announced on Nov. 29, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) has found no causal link between doxycycline, a broad-spectrum antibiotic, and the risk of suicide or suicidal thoughts.

PRAC began a review of the safety of doxycycline in November 2023 after reports of a possible risk of suicidal thoughts or actions with the use of doxycycline from the Finnish national competent authority, as well as other cases reported to the European database of suspected side effects, EudraVigilance. The PRAC review included a cumulative data review from all relevant sources by the marketing authorization holders. There was also a study based on real-world evidence that included data from electronic health records and disease registries.

“After reviewing all available evidence from spontaneous reports, the literature, the discussion on possible mechanisms and the study performed via DARWIN EU [the Data Analysis and Real World Interrogation Network], the PRAC considered that the evidence is not sufficient to establish a causal relationship and that no update to the product information of doxycycline is warranted.

Suicide-related events in relation to doxycycline will be closely monitored and any new evidence will be discussed in the Periodic Safety Update Reports (PSURs),” EMA stated in a press release (1).

During the November meeting, PRAC also agreed to provide a direct healthcare professional communication (DHPC) on the liver injury risks associated with Veoza (fezolinetant). Veoza is used to treat moderate-to-severe vasomotor symptoms (i.e., hot flashes) that occur with menopause. PRAC is recommending that liver function be monitored in patients before and during treatment with fezolinetant. The recommendations are a result of a review of fezolinetant that included information from reports of suspected side effects and published scientific studies. The review showed a potential risk of drug-induced liver injury.

“Severe elevations of the liver enzymes alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (>10x upper limit of normal) with concurrent elevations in bilirubin and/or alkaline phosphatase (ALP) have been reported post marketing in women taking Veoza. In some cases, elevated liver function tests (LFTs) were associated with signs or symptoms suggestive of liver injury such as fatigue, pruritus, jaundice, dark urine, decreased appetite, or abdominal pain.”

Therefore, PRAC is recommending LFTs be performed before treatment is started and monthly tests during the first three months of treatment, with testing conducted thereafter based on symptoms of livery injury. Product information and packaging is being updated with the new safety information.

“Once adopted, the DHPC for Veoza will be disseminated to healthcare professionals by the marketing authorisation holders, according to an agreed communication plan, and published on the 

Direct healthcare professional communications

 in EU Member States,” the agency stated in the release.

1. EMA. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 25-28 November 2024. Press Release. Nov. 29, 2024.

The agency’s safety committee found no sufficient evidence of causal relationship between the antibiotic doxycycline and the risk of suicide or suicidal thoughts.

No Causal Link Between Doxycycline and Suicide, Says EMA Safety Committee 

Cheryl Barton is director of PharmaVision, 

Landkarte *** Europa | Image Credit: © beugdesign - Stock.adobe.com

On 15 Oct. 2024, the European Federation of Pharmaceutical Industries and Associations (EFPIA) published an article to raise industry awareness that the European Union (EU) is developing a roadmap to advance precision oncology at the country level to address the growing burden of cancer in Europe (1). Cancer remains the second biggest cause of death in Europe. In 2024, the predicted mortality cancer rates are forecast to fall by 6.5% in men and by 4.3% in women in the EU (based on data from the five most populous countries and the United Kingdom). However, the number of deaths is still rising, with a total of 1,270,800 predicted deaths in 2024 in the EU and 172,900 in the UK, due to population growth and ageing (2).

New therapies, along with advances in prevention, screening, radiotherapy, and surgery are helping to save lives, but further collaboration, and partnership are needed. The “#WeWontRest until we beat cancer” campaign is underway (3). On 13 Nov. 2024, the EFPIA Oncology Platform organized a stakeholder roundtable in Brussels to bring together EFPIA member companies—AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Ipsen, Johnson & Johnson, Lilly, Novartis, MSD, Menarini, Pfizer, Roche, Sanofi, Servier, and Takeda—to help define future legislative and policy directions to improve the provision of personalized treatment for cancer patients (4).

The event was hosted by the Committee of the Regions, with scientific support from the European Regional and Local Health Authorities (EUREGHA) and Cancer Patients Europe, and aims to bring together stakeholders—policymakers, regional health authorities, patient advocates, and healthcare providers—to explore the challenges to improve access to precision oncology to ensure optimal and timely treatment and overcome healthcare disparities across Europe.

The EU has been developing policies to move toward personalized medicine (PM) and has made significant investments starting in 2010. As of 2017, €3.2 billion was invested in PM research across the medical innovation cycle ‘from bench to bedside’ from the research framework programs FP7 and Horizon 2020 (5).

In 2021, the European Commission (EC) published its cancer plan for Europe outlining several goals to reverse the rising trend of cancer across the EU (

). Europe’s Beating Cancer Plan was the EU’s response to medical needs and aims to tackle the entire disease pathways from prevention, early detection, diagnosis, and treatment, as well as the quality of life of the cancer patients and survivors (6).

EU initiatives in precision medicine in Europe

Many EU initiatives are underway to advance precision medicine in Europe. On 11. Sept. 2024, the Thematic Network on Advancing Precision Medicine for Europe’s Cancer Patients with artificial intelligence (AI)-powered Imaging held a webinar led by the European Society of Radiology to discuss with health stakeholders how AI-powered cancer care can improve personalized treatment strategies and reduce the burden of cancer (7).

Meanwhile, the Digital Oncology Network for Europe (DigiONE) pilot is underway in Europe. An amount of €3 million has been allocated for technology investment in a proof-of-concept learning health system in a precision oncology platform that aims to identify optimal cancer treatments by learning from every patient, not just those in clinical trials, through privacy-preserving interrogation of their standardized routine electronic health records (8,9).

Roadmap for a European cancer data management and precision medicine infrastructure

Aside from the goals laid out in Europe’s Beating Cancer Plan stakeholders recognize that for European citizens to have access to innovative precision medicines there is a need to develop a gold-standard cancer data management system. This will rely on three key elements: adopting standardized data formats; ensuring robust data privacy; educating professionals about the infrastructure’s benefits and leveraging cutting-edge technologies to transform cancer care (10).

Further work is needed to refine the EU roadmap on precision oncology but significant steps have already been taken to put in place the framework to reverse the rising trend of cancer across the EU. Stakeholders should keep abreast of the situation and can access details of the advancing precision oncology agenda in the EU online, via the EFPIA (11).

1. EFPIA. Advancing the Precision Oncology Agenda in the EU: Developing a Roadmap at Country Level to Address the Growing Burden of Cancer in Europe. Guest Blog. 15 Oct. 2024.
2. Santucci, C.; Mignozzi, S.; Malvezzi, M.; et al. European Cancer Mortality Predictions for the Year 2024 with a Focus on Colorectal Cancer. 

35 (3) 308–316.
3. EFPIA. #WeWontRest Until We Beat Cancer. 

Accessed 22 Oct. 2024.
4. EFPIA. Advancing the Precision Oncology Agenda in the EU. Brussels, Belgium. 13. Nov. 2024.
5. Nimmesgern, E.; Norstedt, I.; Draghia-Akli, R. Enabling Personalized Medicine in Europe by the European Commission‘s Funding Activities. 

 14 (4) 355–365.
6. European Commission. 

. Communication Paper, 2021.
7. Nikolski, M.; Hovig, E.; Al-Shahrour, F.; et al. Roadmap for a European Cancer Data Management and Precision Medicine Infrastructure. 

5, 367–372.
8. Mahon, P.; Chatzitheofilou, I.; Dekker, A.; 

 A Federated Learning System for Precision Oncology in Europe: DigiONE. 

 30, 334–337.
9. Nahon. P. Building a Digital Oncology Network for Europe (DigiOne) The Digital Institute for Cancer Outcome Research (DigiCore). 

Accessed 22 Oct. 2024.
10. European Commission. Recording—EUHPP Live Webinar—How to Advance Precision Medicine for Europe’s Cancer Patients with AI-powered Imaging (11 September 2024). News Announcement, 11 Sep. 2024.
11. EFPIA. Advancing the Precision Oncology Agenda in the EU. 13 Nov. 2024

Cheryl Barton is director of Pharmavision, info@pharmavision.co.uk.


Vol. 36, No. 10
November/December 2024
Pages: 9–10

When referring to this article, please cite it as Barton, C. Advancing the Precision Oncology Agenda in Europe. 

The European Commission has developed a roadmap aimed at reversing the rising trend of cancer across the European Union. 

Advancing the Precision Oncology Agenda in Europe

Belgium-based EXO Biologics and its contract development and manufacturing organization (CDMO) subsidiary, ExoXpert, both innovators in exosome-based therapeutics and drug delivery solutions, announced on Dec. 2, 2024,  that ExoXpert has received good manufacturing practice (GMP) certification for its Liège, Belgium, manufacturing facility. At the same time, EXO Biologics achieved the loading of GMP-grade exosomes with messenger RNA (mRNA) and DNA payloads. Both achievements mark significant milestones for the development of exosome-based therapeutics (1).

According to a company press release, ExoXpert is the first European CDMO specializing in exosomes that has received GMP certification (1). The certification was awarded by the Belgian Federal Agency for Medicines and Health Products. Both BioWin, the Health Cluster of Wallonia, Belgium, and the Public Service of Wallonia have been strong supporters of EXO Biologics’ and ExoXpert’s growth, according to the press release.

“We have now achieved two critical strategic milestones by the end of 2024, which extends our continued progress in developing scalable, GMP-compliant solutions for exosome as therapeutic and drug delivery system. This extends our market leading position in the development of exosome-based technologies, unlocking new possibilities for drug delivery, gene therapy, and immunotherapy,” said Hugues Wallemacq, CEO of EXO Biologics, in the press release.

The importance of the GMP certification lays in the official status it gives to ExoXpert’s ability to produce exosomes according to the highest industry standards. The GMP-certified facilities enable EXO Biologics to internalize production of EXOB-001, currently in Phase I clinical development and the first global European Medicines Agency-approved mesenchymal stem cell-based exosome therapeutic in clinical trials. The certification also enables ExoXpert to offer exosome-specialized GMP capabilities internationally, including to current clients in the United States and European Union markets as well as future partners. ExoXpert also has the ability to activate additional cleanroom on demand. The greatest demand for exosomes currently is their use as a safe and non-viral drug delivery system for cell and gene therapy applications, according to the company press release (1).

The second achievement, the successful loading of mRNA and DNA payloads into GMP-grade exosomes, represents a critical step toward developing safe, efficient, and scalable exosome-based therapies for genetic material delivery. While small molecules and short nucleic acids (e.g., small interfering RNA and microRNA) have already been validated in an end-to-end GMP-like setting (2), EXO Biologics’ achievement demonstrates significant progress in the loading of larger molecules (i.e., mRNA and DNA) into GMP-grade exosomes that can then be used for third-party non-viral drug delivery applications. The company’s preliminary trials data have shown a retention rate up to 80% of the loaded DNA cargo upon exosome loading (1).

“The GMP certification of ExoXpert’s Liège manufacturing facility and the successful loading by EXO Biologics of mRNA and DNA into exosomes are major steps in bringing safe and effective exosome-based therapies to patients worldwide. We are now working on optimizing the loading technology to further reduce the manufacturing cost and strengthen the attractiveness of exosome therapeutics and manufacturing compared to alternative classical technologies. This will revolutionize the treatment of complex diseases, including cancer, genetic disorders, and viral infections,” Wallemacq said in the release (1).

1. EXO Biologics. EXO Biologics & ExoXpert Achieve Two Critical Industry-First Milestones for the Exosome Field. Press Release. Dec. 2, 2024.
2. Bhome, R.; Del Vecchio, F.; Lee, G-H.; et al. Exosomal MicroRNAs (exomiRs): Small Molecules with a Big Role in Cancer. 

, 228–235. DOI: 10.1016/j.canlet.2018.02.002

EXO Biologics and ExoXpert, an EXO Biologics subsidiary, have received GMP certification of a European manufacturing facility for exosomes and have successfully loaded mRNA and DNA payloads into GMP-grade exosomes for drug delivery.

Exosomes Field Advances with Milestones Achieved by EXO Biologics and ExoXpert

Lonza has expanded its services to support smart capsule companies developing orally delivered biologics. Oral biologics have unique development and manufacturing requirements, Lonza stated in a Dec. 3, 2024 company press release (1).

Smart capsules are designed to enhance precision, efficacy, and control. They use electronic or mechanical elements to deliver drugs to the stomach or intestine, and their mode of action has the potential to revolutionize the market for oral biologics, Lonza stated in its release (1). There are promising applications for smart capsules in diabetes, obesity, and other therapeutic fields.

To meet the needs of companies developing smart capsule-based therapeutics, Lonza has expanded its offering with a bespoke development and manufacturing service that is focused on the specific needs of smart capsules companies. Through this offering, Lonza leverages its expertise in highly customized capsule solutions that can be tailored to specific requirements, such as size, design, and lock mechanisms. The service also offers a variety of functionalities, including targeted release using a bi-layer manufacturing technology, which can be adjusted to the needs of the respective API.

“The strong market interest in this bespoke offering for smart capsules, marked by the first customer already on board and additional discussions in progress, reinforces the value of our approach,” said Bart Pelgrims, vice-president, R&D, Capsules & Health Ingredients, Lonza, in the release (1). “By ensuring every detail of development, which goes beyond formulation, we are confident in our ability to support smart capsule innovators to help shape the future of healthcare.”

Oral delivery of APIs has traditionally been the route of administration preferred by most patients worldwide. Oral administration has led to improved patient compliance and adherence as well as drug accessibility. Delivering biologics through an oral administration route represents a growing market, and one that is expected to exhibit a 35% compound annual growth rate from 2023–2028, according to Lonza in the press release (1,2). “Since most new drug entities face bioavailability challenges, exploring innovative delivery solutions to mitigate these challenges is of great value to drug developers and their patients,” Lonza stated in the release (1).

Meanwhile, Lonza has also expanded its bioconjugation capabilities at its Visp, Switzerland, site with the addition of two new manufacturing suites (3). In November 2024, the company announced that the new suites will provide additional manufacturing capacity for launch and commercial supply to address growing market demand.

The two new multipurpose 1200-L manufacturing suites and manufacturing-related infrastructure will be added to the site’s existing bioconjugation facility and will double capacity for the launch and commercial supply of bioconjugates. The company expects that the new capacity will be operational starting in 2028 and will generate approximately 200 new jobs (3).

1. Lonza. Lonza Launches Tailored Offering for Smart Capsules Companies Developing Oral Delivery Solutions for Biologic Drugs. Press Release. Dec. 3, 2024.
2. Market Report Manav AI. 

. Lonza Market Intelligence, 2023.
3. Lonza. Lonza to Expand Bioconjugation in Visp (CH) with Two Additional Manufacturing Suites. Press Release. Nov. 12, 2024.

With its new offering, Lonza can tailor services to support smart capsule companies with its bi-layer capsule manufacturing technology.

Lonza to Provide Tailored Offering for the Development of Oral Biologics Using Smart Capsules

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

Edwin Stone, Bernard Sagaert, and Khaled Yamout go behind the headlines to discuss what the ongoing measles outbreak in the UK means for pandemic preparedness and anti-vaccination trends; new mRNA approaches; and what Roche’s acquisition of Poseida means for complex cell therapies. 

Behind the Headlines, episode 7: Pandemic Preparedness, Novel mRNA Applications, and More 

 is a bi-weekly panel discussion examining the latest trends, readouts, and other factors that drive pharmaceutical news and innovation. Each episode features consultants, venture capitalists, scientists, patient advocates, and journalists discussing the prior weeks’ top news while seeking to highlight the more enduring lessons that hide behind the headlines.

In episode 7, Edwin Stone, CEO of Cellular Origins; Bernard Sagaert, CEO of etherna and senior consultant and CEO, Inphacon BV; and Khaled Yamout, founder and CEO of Yamout Chem Consultancy, go behind the headlines to discuss the ongoing 

, and what the troubling trend means for vaccination acceptance and overall pandemic preparedness, including the need for improved public health messaging and narratives to combat anti-vaccination movements globally.

The panel also discussed takeaways from arguably the two most important mRNA conferences of the year, with the Alliance for mRNA Medicines’ (AMM) 1st annual conference, 

, both of which took place in Boston. New mRNA approaches, novel therapeutic applications, and a presentation about a promising branched polyA tail were of great interest for discussion.

Lastly, the panel commented on Roche’s acquisition of its collaboration partner Poseida Therapeutics in an arrangement worth up to $1.5 billion (1), betting on complex immune cell therapies against several types of blood cancer to boost its development pipeline, with Poseida’s non-viral delivery method opening up new avenues in terms of cargo payloads.

Reference: 
1. Poseida Therapeutics, Inc. announces agreement to be acquired by Roche Holdings, Inc. News Release. Poseida Therapeutics. November 26, 2024. https://www.prnewswire.com/news-releases/poseida-therapeutics-inc-announces-agreement-to-be-acquired-by-roche-holdings-inc-302316189.html

Behind the Headlines: Pandemic Preparedness, Novel mRNA Applications, and More

The European Medicines Agency (EMA) reported on Nov. 28, 2024 that the European Shortages Monitoring Platform (ESMP) is now live with core functionalities. ESMP enables marketing authorization holders (MAHs) to submit data to report shortages of centrally authorized medicines in the European Union on a routine basis. Use of ESMP will become mandatory on Feb. 2, 2025, per Regulation 2022/123, which facilitates the exchange of information to prevent drug shortages in the EU.

A second version of the ESMP will be released in February 2025 and will include full functionality for MAHs and national competent authorities to submit data on supply, demand, and availability of centrally and nationally authorized drugs during crises actions set forth by EMA’s Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG). These types of actions are taken by MSSG to monitor and mitigate potential shortages of important medicines.

“The release of the ESMP is a major milestone in the effort to tackle medicine shortages and ensure that medicines are available to patients when and where they need them most,” the agency stated in a press release (1). “It will centralize and automate data collection on medicine shortages, giving regulatory authorities access to real-time, comprehensive information to improve the prevention, monitoring, and management of medicine shortages across the EU and the European Economic Area (EEA).”

MAHs are encouraged to become familiar with the ESMP before it becomes mandatory. EMA is offering training, webinars, and information material on its website. The agency will also be providing updates on timelines and developments on its website at 

https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/medicine-shortages-availability-issues/european-shortages-monitoring-platform

More information about drug shortages in the EU can be found on EMA’s Medicine Shortages Single Point of Contact (SPOC) Working Party webpage (2). SPOC monitors and reports on events that may impact the drug supply in the EU. Information on ongoing and resolved shortages can be found on the webpage as well as registries of shortages by EU Member State. The agency lists 30 drugs as currently short in supply.

Drug shortages can be caused by a variety of problems, including quality control issues at manufacturing plants, high product demand, and natural disasters across the world. In June 2024, EMA and the Heads of Medicines Agencies issued recommendations to address the shortage of glucagon-like peptide-1 (GLP-1) receptor agonists due to a surge in demand (3).

“Member States should consider, jointly with marketing authorization holders, measures to control and optimize the distribution of these medicines. Member States’ continuous collaboration and cooperation through the [SPOC] will allow the MSSG to gain a comprehensive overview of the situation and assess the impact of the measures taken. Member States are also encouraged (together with experts and learned societies) to develop guidelines to facilitate prioritization of patients who have the greatest need for the medicines,” the agency stated in the release (3).

In late 2024, a series of intense storms hit the United States, causing damage to manufacturing facilities (4). Baxter had to close its facility in North Carolina, which is the largest manufacturing site for intravenous and peritoneal dialysis solutions in the US (5,6).

EMA. European Shortages Monitoring Platform Enables Better Monitoring of Shortages in the EU. Press Release. Nov. 28, 2024.

EMA. Medicine Shortages Single Point of Contact (SPOC) Working Party. 

https://www.ema.europa.eu/en/committees/working-parties-other-groups/medicines-shortages-single-point-contact-spoc-working-party

Baxter. Baxter Provides Update on North Cove, N.C., Facility and Hurricane Helene Relief Plans for Community. Press Release, Sep. 29, 2024.

Baxter. Hurricane Helene Updates. Press Release, Oct. 21, 2024.

A new platform allowing market authorization holders to report drug shortages has gone live. 

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