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

Cheryl Barton is director of PharmaVision, 

Two dosing pens of a fictitious semaglutide drug (GLP-1) on a scale facing a dumbbell. Concept for alternative ways to loose weight. | Image Credit: © Andreas Prott - Stock.adobe.com

Obesity is a major public health threat and is associated with an increased risk of obesity-related complications and mortality. It has proved a challenging target for pharmaceutical intervention, and early strategies using amphetamine-based appetite suppressants resulted in significant side effects and high-profile lawsuits against manufacturers (1).

Better understanding has fuelled product development

A better understanding of the gut-brain axis has led to the development of oral glucagon-like peptide-1 (GLP-1) receptor agonists (RA) and glucose-dependent insulinotropic polypeptide (GIP) RAs for the treatment of type 2 diabetes (T2D) and weight management (

). These include Novo Nordisk’s oral Ozempic/Wegovy (semaglutide) and Saxenda (liraglutide) and Eli Lillys’ once-weekly GIP/GLP-1 dual agonist Mounjaro (tirzepatide), which was approved by the European Medicines Agency (EMA) in 2202 to manage weight (2,3).

Regulatory-approved anti-obesity medicines.

Next-generation anti-obesity medicines are emerging

GLP-1 agonists and GIPs are not without their side effects, so companies are researching new drug targets, combinations, and formulations to overcome these shortfalls and provide safer, more robust, and sustainable body weight loss (3-6). According to IQVIA, 116 new anti-obesity medicines (AOMs) are in clinical development (

). Several of the agents modulate novel targets such as amylin, cannabinoid receptor type 1 (CB-1), diacylglycerol O-acyltransferase 1 (DGAT1), monoacylglyceroltransferase (MGAT2), and solute carrier 6 (SLC6) transporters.

 Anti-obesity agents in clinical development. 

European biotechs active in the AOM space

The AOM space has attracted a lot of attention from pharma and biopharma leading to some high-profile acquisitions during 2024 including US-based Carmot Therapeutics by Roche and US-based Versanis Bio by Eli Lilly and UK Biotech Zihipp by Metsera (7–9). Several European biotechs are making headway in this arena (

), and private investors are keen to get in on the act.

Anti-obesity medicines in clinical development from European biotechs.

European companies worth watching out for in the AOM space include the following.

The company’s lead programme, AT-7687, is a once-weekly subcutaneously administrated GLP-1 receptor peptide antagonist that binds strongly to albumin circulating in the blood to extend its half-life (10). In December 2024, Antag gained US Food and Drug Administration (FDA) investigational new drug (IND) clearance to advance to Phase I in early 2025. The company is evaluating AT-7687 as a monotherapy and in combination with Novo Nordisk’s Ozempic/Wegovy (semaglutide) (11). Antag recently completed an €80 million (US$82.4 million) Series A financing round backed by Versant Ventures and Novo Holdings, and the funds will be used to drive the development of AT-7687 (12). In January 2025, Antag announced that Joerg Moeller formerly of Bayer would succeed Alexander Sparre-Ulrich as chief executive officer, who will move to the chief operating officer role to drive the GLP-1 programme forward.

 Gubra is a pre-clinical contract research organization (CRO)/biotech founded in 2008 and focusing on peptide-based therapies. Its lead program, GUBamy, is a long-acting amylin analogue that is well-tolerated and significantly increased weight loss during the six-week Phase I study (13). Gubra is developing four anti-obesity agents in conjunction with Boehringer Ingelheim (BI) including two clinical progammes with a long-acting neuropeptide Y receptor type 2 (NPY2R) agonist, BI 1820237, and a triple agonist. In October 2024 BI discontinued its development of BI 1820237, and no further details were released (14). In December 2024, Gubra announced a new collaboration with Amylyx Pharmaceuticals to develop a novel long-acting GLP-1 receptor agonist (15). Under the agreement, Gubra will receive upfront and research payments and may receive more than US$50 million (€48 million) on milestones payments and royalties on worldwide net sales. In January 2025, Gubra announced it had appointed Anne-Marie Levy Rasmussen as the company’s new chief operating officer (previously at GlaxoSmithKline and Bavarian Nordic) to help grow and optimize the company (16).

 Verdiva Bio is a private cardiometabolic health company founded in 2024 and headed up by Khurem Farooq, Farooq, formerly chief executive of Aiolos Bio, and Gyroscope Therapeutics before their respective acquisitions by GlaxoSmithKline and Novartis, respectively. In January 2025, Verdiva Bio completed a US$411 million (€391 million) Series A financing co-led by Forbion and General Atlantic, with additional participation from RA Capital Management, OrbiMed, Logos Capital, Lilly Asia Ventures, and LYFE Capital (17). In January 2025, Verdiva acquired global development and commercialization rights outside of greater China and South Korea to their industry-leading portfolio from Sciwind Biosciences in 2024. The partnered portfolio includes:

VRB-101, a Phase II-ready, once-weekly oral GLP-1

VRB-103, a once-weekly, oral dual-acting amylin and calcitonin receptor against (DACRA) agent in preclinical development for use as monotherapy or in combination with VRB-101

VRB-102, once-weekly injectable DACRA for use in combination with VRB-101 in pre-clinical development (18).

 The biopharma company was founded by Bjarne Due Larsen, Lars Hellerung Christiansen, Leif Helth Jensen, Dan Buxbom, and Florian Schönharting in 1997 as Peptide Probe Technologies ApS, focused on the design and development of peptide-based medicine. In June 2024, Zealand Pharma completed an upsized equity offering of 8.35 million new ordinary shares raising DKK 7 billion (US$1 billion) to fund the development of its pipeline (19). The company is developing several AOMs including a long-activating amylin analogue, petrelintide (ZP8396), and GLP-1/GLP-2 receptor dual agonist, dapiglutide. In the first half of 2025, the company expects to initiate a Phase IIb trial with petrelintide in overweight or obese patients without T2D, and a Phase Ib combination trial with petrelintide and dapiglutide (20–21). In January 2025, the company appointed Steven R. Smith, MD as senior global medical advisor in Obesity to help advance Zealand’s peptide-based assets (22).

 January/February2025 digital issue. It was later published in 

The pharma and biotech industry continues to explore new modalities and targets that modulate the brain-gut axis. Late in 2024, Sanofi strategically invested in Italy-based Resalis Therapeutics to gain access RES-010, a first-in-class antisense oligonucleotide targeting miR-22, that plays a pivotal role in the molecular pathways underlying obesity (23). Meanwhile, scientists at the National Cancer Research Centre (CNIO), USA have identified a new mitochondrial protein (MCJ/DnaJC15) involved in brown fat thermogenesis that may present promising new targets for obesity and related metabolic disorders (24). There is still significant room in the multi-billion AOM market to make a mark.

1. Dolgin, E. A History of Drugs on the Weight List. 

 6 Jun.
2. Melson, E.; Ashraf, U.; Papamargaritis, D.; et al. What is the Pipeline for Future Medications for Obesity? 

. https://doi.org/10.1038/s41366-024-01473-y
3. IQVIA. A Look at the R&D Landscape in Obesity, Led by GLP-1s. 

, 19 March 2024.
4. Garza, M. FDA Approves Mounjaro (Tirzepatide) for Diabetes Treatment. 

. 13 May 2022.
5. Müller, T.D.; Blüher, M.; Tschöp, M.H.; et al. Anti-obesity Drug Discovery: Advances and Challenges. 

, 21, 201–223.
6. Quarta, C.; Cota, D. Anti-obesity Therapy with Peripheral CB1 Blockers: From Promise to Safe(?) Practice. 

, 44 (11), 2179–2193.
7. Carmot Therapeutics. Carmot Therapeutics Announces Completion of Acquisition by Roche. News Release. 29 Jan. 2024.
8. Eli Lilly. Lilly to Acquire Versanis to Improve Patient Outcomes in Cardiometabolic Diseases | Eli Lilly and Company. News Release. 14 July 2024.
9. Taylor, P. Metsera Lands with $290m to Take on Obesity Giants. Pharmaphorum. 19 April 2024.
10. Jensen, M.H.; Sanni, S.J.; Riber, D.; et al. AT-7687, a Novel GIPR Peptide Antagonist, Combined with a GLP-1 Agonist, Leads to Enhanced Weight Loss and Metabolic Improvements in Cynomolgus Monkeys. 

, 88, 102006.
11. Antag Therapeutics Antag Therapeutics Announces €80 Million Series A Financing. News Release. 4 Dec. 2024.
12. Antag Therapeutics. Antag Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application for Lead Molecule, AT-7687. News Release. 9 Oct. 2024.
13. Gubra. Gubra announces positive GUBamy Phase 1 SAD data (correction). News Release. 13 Nov. 2024.
14. Gubra. Gubra Announces New Collaboration with Amylyx Pharmaceuticals to Develop a Novel Long-acting GLP-1 Receptor Antagonist. News Release. 30. Dec. 2024.
15. Gubra. Gubra Announces Discontinuation of Development of NPY2R in Obesity with Boehringer Ingelheim. News Release. 31 Oct. 2024.
16. Gubra. Gubra Appoints New Chief Operating Officer. News Release. 15 Jan. 2025.
17. Verdiva Bio. Verdiva Bio. News Release. 9 Jan. 2024.
18. Scimind Biosciences. Sciwind Biosciences Announces Global Licensing and Collaboration Agreement for Metabolic Disease Portfolio. 10 Jan. 2025.
19. Zealand Pharma. Zealand Pharma Announces Completion of an Upsized Equity Offering of 8.35 million New Ordinary Shares Raising Proceeds of USD 1 billion/DKK 7 billion. News Release. 25 Jun. 2024.
20. Zealand Pharma. Zealand Pharma Announces the First Participant Enrolled in People with Overweight or Obesity. News Release. 10 Dec. 2024.
21. Zealand Pharma. Zealand Pharma Announces Positive Topline Results From 13-Week Phase 1b Multiple Ascending Dose Clinical Trial With GLP-1/GLP-2 Receptor Dual Agonist Dapiglutide. News Release.
22. Zealand Pharma. Steven R. Smith, MD, joins Zealand Pharma as Senior Global Medical Advisor in Obesity. 7 Jan. 2025.
23. Resalis Therapeutics. Resalis Therapeutics Gains Strategic Equity Investment from Sanofi. News Release. 28 Oct. 2024.
24. Cicuéndez, B.; Mora, A.; López, J.A.; et al. Absence of MCJ/DnaJC15 Promotes Brown Adipose Tissue Thermogenesis. 

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


Vol. 37, No. 1
January/February 2025
Pages: 16–17

When referring to this article, please cite it as Barton, C. Next-Generation Anti-Obesity Medicines. 

Articles

European biopharma companies are looking beyond GLP-1s.

Next-Generation Anti-Obesity Medicines

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role 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

Recipharm, a Stockholm, Sweden-based contract development and manufacturing organization (CDMO), announced on Feb. 5, 2025 that a new and advanced modular sterile filling system, which performs aseptic filling within a Grade A isolator, is now fully operational and operates in full compliance with good manufacturing practice (GMP) standards. The system is tailored for process development and is located at the company’s facility in Wasserburg, Germany (1).

According to the company, the system’s interchangeable modules supporting various product types, such as syringes and vials, help to increase flexibility, and an additional pre-filled syringe module that is included with the installation broadens the capabilities of the system even further (1).

Recipharm said the filling line can deliver anywhere from 500 to 50,000 units per batch, making it useful for all development phases (1). The system is also designed to limit loss of high-value products to less than 500 mL, preserving material for clinical trials and ultimately providing cost savings.

“With this unit, we offer our clients a flexible, high-quality and GMP-compliant solution for their development and clinical production needs,” Gregor Kawaletz, Recipharm chief commercial officer, said in the press release (1). “This installation reflects our commitment to investing in innovative technologies that enable faster and more efficient pharmaceutical development.”

Installation was performed during the summer of 2024, and the system has already successfully completed its first production run for a leading biotech company, although Recipharm did not identify that company by name.

 for the pharmaceutical industry at the beginning of 2025, Pharmapack and CPHI said that the ongoing demand for glucagon-like peptide-1 (GLP-1) drugs would cause aseptic filling capacity to be “tied up” in these drugs’ clinical filling needs, especially with generic GLP-1s entering the market in 2025 (2). This, Pharmapack said, could cause delays in the clinical filling of other therapies with smaller volumes.

“The result is that we will see biotechs widening supplier networks and potentially even Big Pharma searching for new partners for GLP-1s,” Pharmapack said at the time. “Consequentially, contract and device filling is predicted to be a rapid growth area.”

®’s coverage of Pharmapack 2025 can be viewed here.

® had the opportunity to speak to Uwe Hanenberg, Recipharm head of product implementation, about trends, technological advancements, and industry investments (3).

In that interview, Hanenberg predicted the increased need for efficient commercial production capabilities in 2025, specifically noting the burgeoning popularity of GLP-1 diabetes and weight loss drugs.

“There will come further big products. And that is certainly not to be executed on an existing tablet line or blister line,” Hanenberg said at the time (3). “That is something where you need more investment … I expect to see announcement on investment in high-potent capabilities, especially in [the] CDMO space, anything that is related to completion of offerings to reach an integrated solution, which means I expect a further consolidation of the CDMO market. Then I expect a very significant investment in continuous manufacturing. There are big companies who have a commitment to produce, in future, 50–80% of all new launches on continuous manufacturing.”

Watch the full interview with Hanenberg here.

1. Recipharm. Recipharm Expands Aseptic Filling Capabilities for Process Development, Pilot Scale and Clinical Supply. Press Release. Feb. 5, 2025.
2. Mirasol, F. 

Pharmapack Reports on Key Trends for 2025.

CPHI Milan 2024: Trends in Oral Solid Dosage Forms.

Installation was performed during the summer of 2024, and the system has already successfully completed its first production run for a leading biotech company.

Recipharm Launches New Fully Operational Modular Sterile Filling System in Germany

AdvanCell, a Sydney, Australia-based, clinical-stage radiopharmaceutical company founded in 2019 that specializes in the development of cancer therapeutics, has successfully completed an oversubscribed, $112 million round of Series C financing (1). The company announced the milestone in a press release on Feb. 3, 2025.

Funding was co-led by SV Health Investors, Sanofi Ventures, Abingworth, and SymBiosis, with additional support from existing investor Morningside and new investors Tenmile and Brandon Capital, among others (1).

“We are delighted to support AdvanCell’s growth and play a role in its remarkable journey through leading this oversubscribed Series C,” Jamil M. Beg, partner at SV Health Investors, said in the AdvanCell press release (1). “The company’s exceptional team, technologies, robust infrastructure, collaborations with some of the world’s largest pharma companies, and ability to consistently execute position it to truly change outcomes for patients.”

Beg has joined the AdvanCell board of directors as part of the financing, along with Christopher Gagliardi of Sanofi Ventures and Bali Muralidhar of Abingworth (1).

The mission of AdvanCell was originally built around targeted alpha-emitting radionuclides for cancer therapy, and, to that end, the company currently operates a 40,000-square-foot manufacturing facility, with a workforce of 60 (1). AdvanCell plans to expand manufacturing capacity even further and accelerate clinical development of its radionuclide therapy pipeline with the Series C funding.

Patient enrollment is currently underway for the highest-dose cohort of a multi-center, Phase I/II dose escalation clinical trial of ADVC001, which AdvanCell said may be a potentially best-in-class targeted alpha therapy for metastatic prostate cancer. According to the press release, the aim of the trial is to demonstrate the safety and efficacy of radionuclide treatment based on Pb-212, a lead isotope (1).

“This successful Series C round demonstrates strong confidence in our vision and capabilities,” said Andrew Adamovich, CEO of AdvanCell, in the press release (1). “We are grateful for the continued support from our existing investors, particularly the long-term support from Morningside and are excited to welcome new partners who share our commitment to transforming cancer care. With this funding, AdvanCell is well-positioned to scale our manufacturing operations and progress our cutting-edge therapies towards commercialization.”

Elsewhere in Australia, the nonprofit organization Genetic Cures for Kids 

 with United States contract development and manufacturing organization PackGene Biotech, and the Belfer Gene Therapy Core Center at Weill Cornell Medicine, to deliver an accessible, custom-tailored gene therapy solution for treating hereditary spastic paraplegia type 56, an ultra-rare neurological disease, as announced by PackGene on Jan. 8, 2025 (2).

Additionally, North Melbourne-based Telix Pharmaceuticals 

 that it had entered into an asset purchase agreement with ImaginAb, of Inglewood, Calif. in the US, to acquire a pipeline of next-generation therapeutic candidates and a protein engineering and research facility (3).

On the cancer front, the European Commission 

 as of Jan. 21, 2025 for two Johnson & Johnson treatments for advanced non-small cell lung cancer, Lazcluze (lazertinib) in combination with Rybrevant (amivantamab) (4). And on January 22, 

 that the National Institute for Health and Care Excellence gave positive recommendations to its Imfinzi (durvalumab) and Tagrisso (osimertinib) for treatment of lung cancer patients in England and Wales (5).

1. AdvanCell. AdvanCell Successfully Completes an Oversubscribed US$112M Series C Financing. Press Release. Feb. 3, 2025.
2. PackGene Biotech. A Global Alliance to Save Lives: How Two Parents and PackGene Are Redefining What’s Possible in Gene Therapy with Help from Weill Cornell Medicine. Press Release. Jan. 8, 2025.
3. Telix Pharmaceuticals. Telix to Acquire Next-Generation Therapeutic Assets and Innovative Biologics Technology Platform. Press Release. Jan. 13, 2025.
4. Johnson & Johnson. European Commission Approves Lazcluze (lazertinib) in Combination with Rybrevant (amivantamab) for the First-Line Treatment of Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer. Press Release. Jan. 21, 2025.
5. AstraZeneca. AstraZeneca Receives Two Positive NICE Recommendations for Lung Cancer Patients Across England and Wales. Press Release. Jan. 22, 2025.

Patient enrollment is currently underway for the highest-dose cohort of AdvanCell’s potentially best-in-class targeted alpha therapy for metastatic prostate cancer.

AdvanCell Completes $112 Million Oversubscribed Series C Financing

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

In this interview, Pharmaceutical Technology® discusses the trend of AI in pharma and how it may play out in 2025 and beyond with Ben Sidders from Biorelate.

Industry Outlook 2025: The Rising Prominence of AI in Pharma

“Undoubtedly, 2024 was the year of AI [artificial intelligence] in pharma,” notes Ben Sidders, chief scientific officer for Biorelate—an AI platform company that provides data solutions to pharma companies—when discussing the key trends of the year. This trend has manifested in several ways, he notes, from the rise of AI-first companies that have shifted the way drug discovery is undertaken, to the increasing use of AI across traditional pharma processes, and the rise of digital health and the use of real-world data.

“AI will obviously continue to rise in prominence and to dominate, and I think this will be driven by three major areas,” Sidders continues. “So, the first is data and its availability, but also the maturation of pharma’s data strategies. [… The] second area is really around the models that are available. I think the realization has been quite clear that causality is key, and so we need to develop a move towards [AI] approaches that embed the underlying causality […]. And then finally, I think probably it's around the culture. So, the culture of these pharma companies will continue to develop in 2025, really adopting a new paradigm driven by a top down mandate, where AI is put at the center of the research programs, [and] also of organizational design […]. And I think if all of this happens, then we'll actually start to realize some of the value and the efficiencies from AI, and I think that evolutionary process of adopting AI into pharma will really start to fulfill the promise, and maybe not all of the hype, but some of the hype that's been around over the last few years.”

Dr. Ben Sidders, Chief Scientific Officer for Biorelate

Dr. Ben Sidders is the Chief Scientific Officer for Biorelate, which is an AI platform company that provides data solutions to pharma companies. Ben has 20 years of experience in industry, working for both AstraZeneca and Pfizer, most recently as the head of data science for AstraZeneca oncology research functioning.

Videos

Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.

Hand of young man with pill, closeup. Image Credit: ©Africa Studio - stock.adobe.com

The careful design and development of formulated oral drug products are key to ensuring patient acceptability and compliance for achieving the desired clinical outcomes. Many APIs are extremely bitter or have other aversive attributes that can make developing palatable drug products challenging, notes Nazim Kanji, executive director of pediatric services with Quotient Sciences. Several factors can influence palatability, including the chemical structure of the drug substance and the finished medicinal product formulation, as well as the excipients used. “Undesirable taste is a common problem seen in medicines spanning all therapeutic areas, from antibiotics and painkillers to antihistamines and decongestants,” Kanji notes.

Taste masking of oral dosage forms is, therefore, an essential component of formulation development. A one-size-fits-all approach is not available, however, according to Ashish A. Joshi, pharma technical and business manager with BASF Pharma Solutions. Taste-masking strategies, he observes, must almost always be tailored to various aspects, such as the degree of inherent bitterness of the drug, the type of dosage form, the patient age-group, and whether the final formulation is in a solid or liquid form.

As the percentage of drug substances in development suffering from bitter tastes has increased and many new formulation and delivery strategies have been introduced to increase patient convenience and compliance, taste-masking technology has therefore evolved. In addition to more traditional approaches such as the use of barrier coatings, solid dispersions, and the addition of sweeteners and flavoring agents, formulators are leveraging newer strategies such as liposomes, various forms of complexation, co-crystal and pro-drug formation, emulsification, and microsphere and encapsulation technologies.

As part of developing palatable pediatric and patient-centric drug products such as solutions, suspensions, and orally disintegrating tablets (ODT), several recognized approaches can be taken to mitigate the poor taste of these APIs. “The most common approaches include using a combination of flavors and sweeteners to mask a bitter taste or barrier coatings to prevent the release of API from the drug product into the buccal cavity prior to the dose being swallowed,” comments Kanji.

Some advances in taste-masking technology are improving on these basic approaches. Researchers are, for instance, exploring methods to enhance both the perception and physicochemical stability of long-acting flavors through encapsulation and complexation techniques, according to Joao Marcos Assis, global technical marketing manager at BASF Pharma Solutions. Joshi adds that certain zinc salts have also demonstrated the ability to mask bitter taste effectively.

Improvements in pH-dependent barrier film coatings, meanwhile, have helped to overcome the coating inefficiencies for fine (small particle size) drug substances that require extended processing times due to their large surface areas. For these APIs, additional steps or approaches such as drug granulation to increase particle size or drug layering in inert pellets, can be used, Assis observes.

Lipids and insoluble polymers such as stearic acid, ethyl cellulose, and carnauba wax, when used in combination with surfactants, have also been shown to be promising as effective taste-masking approaches for drug particles. “These hydrophobic materials have low solubility in the mouth, contributing to improved taste-masking properties,” Joshi explains. He does caution, though, that it is important to be aware that use of lipid coatings may result in changes in a drug substance’s release profile, thus potentially impacting drug bioavailability.

Reverse-enteric polymers have become increasingly attractive as taste-masking polymers due to their pH-dependent solubility; they do not dissolve in the mouth at salivary pH, but once exposed to the acidic pH of the stomach, dissolve immediately to release the drug substance.

When these types of polymers are employed, the coating composition and level must be carefully balanced to prevent drug release during the residence time in the buccal cavity (e.g., up to 30 seconds for orally disintegrating tablets) while still allowing adequate drug release in the gastrointestinal tract to ensure that pharmacokinetic (PK) performance is not compromised, according to Kanji. “Realizing this balance can be a challenging prospect and may not be accurately predicted by in vitro dissolution testing,” he observes.

One example noted by Assis is a copolymer of methyl methacrylate (MMA) and diethylaminoethyl methacrylate (DEAEMA), which exhibits a lipophilic characteristic and does not dissolve at neutral to basic pH due to the amino functional group. “This lipophilic quality is very beneficial to the process [because] it reduces the required coating level for taste-masking purposes and provides moisture protection for sensitive drugs,” he observes. With these attributes, the drug substance becomes more suitable for liquid taste-masked formulations, where well-coated particles can be suspended in a neutral pH liquid, enabling the creation of a taste-masked suspension.

In the dry-powder form, water-insoluble matrices have been used effectively in melt-granulation processes, Joshi adds. During extrusion, the polymer covers the drug substance and forms a stable barrier layer once the granules are cooled. “The key advantage of this process is that it does not use any water or solvents and thus achieves efficient taste-masking of a moisture-sensitive drug substance while minimizing its possible degradation due to exposure to an aqueous or organic coating process,” he comments.

Another benefit to melt-granulation is the reduced process time compared to film coating, according to Assis. It can also be implemented as a continuous process, he notes. Reverse-enteric polymers in the dry state may also be suitable for the development of hot-melt extrusion formulations, allowing the production of taste-masked amorphous solid dispersions with improved solubility and taste, Assis remarks.

Using a mixture of water-soluble and insoluble polymers represents another newer strategy. “Tailoring the ratio of a polyvinyl acetate (PVAc)-based water-insoluble polymer and a water-soluble pore former such as a polyvinyl alcohol-polyethylene glycol (PVA-PEG) copolymer in a barrier coating allows efficient taste-masking to be achieved without significantly altering the release profile of the formulation,” Joshi explains.

The assessment and optimization of the polymer coating can be efficiently undertaken by integrating drug product formulation development and manufacturing with clinical testing activities, says Kanji. Quotient Sciences, for instance, uses a proprietary drug-development platform that enables drug products to be manufactured, released, and dosed in healthy subjects in a matter of days so that compositions can be optimized based on emerging clinical data. In addition to PK data, each formulation’s palatability attributes (e.g., bitterness, mouthfeel, grittiness, and aftertaste) can also be assessed as part of the same study, Kanji adds.

Following development of the taste-masked dosage form, confirmation of acceptability is achieved via palatability assessment of the drug product, thereby providing assurance that poor taste will not impact patient acceptability and compliance, Kanji concludes.

Lipid excipients are also being explored as encapsulating agents. One example highlighted by Joshi involves dispersing the drug substance in molten stearic acid or glycerol monostearate followed by atomization in a cold environment using a melt-congealing microencapsulation process. “This approach is particularly useful when the API is both extremely bitter and highly sensitive to moisture because it allows for effective taste-masking without the use of a typical aqueous barrier coating,” he contends.

Masking the taste of highly bitter drug substances in liquid dosage forms (solutions or suspensions) remains a significant challenge. Despite advances, effective taste masking can still be difficult when a drug substance has multiple taste and/or sensorial attributes (e.g., bitter, metallic, burning sensation), according to Kanji. This situation is particularly true for liquid formulations, which typically rely on the use of flavors and sweeteners for taste masking, he notes. Barrier coatings may also lose their effectiveness over the shelf-life of the product due to continuous exposure of the API to water, Joshi adds.

One new solution is to use micelle-forming surfactants, liposomes, or cyclodextrins to protect the drug substance. “For instance, in an aqueous environment,” Joshi comments, “certain surfactants and poloxamers form micelles that can entrap the drug substance, forming transient inclusion complexes, thus shielding it from the tastebuds and effectively masking its taste. This approach, he observes, also has potential for use in other dosage forms, such as gummies.

The use of water-in-oil (W/O) emulsions for taste masking of soluble APIs is another promising approach for liquid formulations, according to Assis. “In this case, the drug substance is effectively encapsulated within the water phase, which is surrounded by the continuous oil phase, preventing it from coming in direct contact with the taste buds and thus masking unpleasant tastes such as bitterness,” he says.

The water-soluble API is dissolved in the aqueous phase. The continuous phase comprises an oil with an acceptable taste profile, with medium-chain triglycerides (MCTs) being of particular interest, as well as surfactants with both low and high hydrophilic–lipophilic balances (HLBs) as the emulsifiers, Assis observes. He notes that polyoxyl 40 hydrogenated castor oil with a high HLB of approximately 14 to 16 is recommended for solutions and suspensions because, unlike other emulsifiers, it has a more pleasant taste. Additionally, glycerol monostearate type II (mono- and di-glycerides) is an excellent alternative as a co-emulsifier due its low HLB value of approximately 3.8.

The water phase is dispersed within the continuous oil phase, and the resulting O/W emulsion has the drug substance “hidden” within the emulsion droplets, which act as a barrier between the API and the taste receptors, Assis says. The oil phase surrounding the water droplets, meanwhile, prevents release of the drug substance while it is in the mouth; release occurs only once emulsification and absorption take place in the gastrointestinal tract.

Solutions for high drug-loading formulations

One important trend in oral dosage drugs is development of high-drug-loading formulations. “High-dose drugs in solids can be very tricky and demand better approaches to improve their taste profiles,” Joshi says. For instance, he notes, traditional barrier coatings can be challenging as long coating processing times are often required to achieve the desired level of masking.

One alternative is to use a dual-granulation coating approach to establish a barrier coating. “In this process,” explains Joshi, “the coating polymer not only covers the API and excipients, but also acts as a binder that enables formation of larger granules. The result is effective taste masking combined with improved flowability and compressibility of the drug product.” It is necessary, though, to use appropriate cushioning agents/plasticizers to maintain the integrity of the polymer following compression into a tablet. Certain methacrylic acid polymers can be effectively used in this application.

Development of additives for oral dosage drugs that block the receptors in the mouth that perceive bitterness has been a goal for many years. Taste buds elicit taste responses using G-protein coupled receptors (GPCR) or ion-channel receptors. Modulating their responses using compounds that block these receptors would be an effective means of eliminating the perception of specific tastes, according to Joshi.

This approach remains challenging, however. Such compounds need to be safe and provide transient and reversible modulation so that a patient’s taste perception is not affected for a long time after consuming the drug, Joshi says. In addition, there are at least 25 different, highly genetically diverse bitter taste receptors, and the drug substance-taste receptor pathway is not always known, Assis observes. Despite these challenges, a few specific compounds referred to as bitter blockers have been developed that interfere with the taste transduction process, at least to some degree, by inhibiting the taste cascade (interrupting the GPCR signal cascade), says Assis.

A few other approaches are also being explored. For instance, the API, which typically exists as a salt of some kind, can be converted into a more palatable compound, such as a prodrug, freebase, or different salt, according to Assis. It is necessary when using this strategy, however, to carefully consider the formulation development time and to assess any potential changes in pharmacokinetics.

Finally, complexing agents like ion-exchange resins and cyclodextrins can be used to prevent interaction of the API with bitter receptors. When using these approaches, Assis emphasizes the importance of considering factors such as the potential for drug-resin dissociation and the amount of cyclodextrin needed, respectively, as these factors may impact dosage size and costs. Cyclodextrin, for instance, can not only be very costly, but also may need to be used in a high quantity to ensure effective complexation with the drug substance at the molecular level.

Cynthia A. Challener, PhD, is a contributing editor to Pharmaceutical Technology®.

®
Vol. 49, No. 1
January/February 2025
Pages: 17–19

When referring to this article, please cite it as Challener, C.A. Evolving Approaches to Taste Masking. 

Increasing API and formulation complexity and new delivery strategies are driving innovations in taste-masking.

Evolving Approaches to Taste Masking 

Belgium-based Ardena announced on Feb. 4, 2025 that it had successfully completed the acquisition of a state-of-the-art drug product manufacturing facility from Catalent. The facility is located in Somerset, NJ, in the United States, according to an Ardena press release (1).

Ardena, a pharmaceutical contract development and manufacturing organization (CDMO) and bioanalytical contract research organization, said in the release that the transaction furthers the company’s strategic expansion into North America, enhancing its suite of drug development services—particularly late-stage, small-scale commercial manufacturing of oral drug projects (1).

“This acquisition reflects our ongoing commitment to supporting biopharma innovators at every stage of drug development,” Jeremie Trochu, Ardena CEO, said in the press release. “The addition of the Somerset facility strengthens our ability to provide tailored, high-quality development and manufacturing solutions to our clients, while accelerating the international expansion of our fast-growing bioanalytical business.”

The New Jersey facility is comprised of more than 50,000 square feet of current good manufacturing practice space and is a recognized Center of Excellence for advanced oral dosage forms, according to the release (1).

Ardena intends to open a new bioanalytical lab on the Somerset site, as part of expanding services the company offers in that region in North America. Plans outlined in the press release call for the lab to have a 2500-square-foot capacity and provide advanced analytical testing services for both small and large molecules, including platforms supporting immunochemistry, liquid chromatography coupled to tandem mass spectrometry, flow cytometry, and quantitative polymerase chain reaction (1). There are currently more than 200 workers on staff at the Somerset site.

“We are thrilled to officially welcome the Somerset team into the Ardena family,” Trochu said. “Their deep scientific and technical expertise, their impeccable regulatory track record, and unwavering dedication to excellence align perfectly with our mission of helping clients bring life-changing treatments to patients quickly and efficiently.”

In October 2024, Ardena announced a strategic investment in two sites in the Netherlands: a brand-new bioanalytical laboratory at its Pivot Park facility, located in the city of Oss, as well as added capacity and new good laboratory practice capabilities at its Bioanalytical Center of Excellence in Assen (2). Meanwhile, at the beginning of 2025, Catalent was 

 as one of five CDMOs to watch in the year ahead (3).

Ardena’s acquisition of the Catalent site is the latest of several developments with facilities in New Jersey. In November 2024, 

Avantor opened a new, flagship Innovation Center

 in Bridgewater, NJ, a 60,000-square-foot, state-of-the-art R&D space (4). Previous to that, in July 2024, BeiGene opened an $800 million biologics manufacturing facility at the Princeton West Innovation Campus, in Hopewell, NJ, intended to be that company’s flagship facility in the US. The Hopewell site also houses a clinical R&D center (5).

The new bioanalytical lab being opened by Ardena at the Somerset site is expected to be operational by the third quarter of 2025, according to the Ardena press release (1).

1. Ardena. Ardena Completes Acquisition of Advanced Drug Product Manufacturing Facility from Catalent and Expands Bioanalytical Services in North America. Press Release. Feb. 6, 2025.
2. Ardena. Ardena Expands Bioanalytical Services in Europe. Press Release. Oct. 29, 2024.
3. Bigica, A. 

, Jan. 2, 2025.
4. Avantor. Avantor Opens New Bridgewater Innovation Center Focused on Solving Life Science’s Biggest Challenges. Press Release. Nov. 14, 2024.
5. BeiGene. BeiGene Opens Flagship US Biologics Manufacturing and Clinical R&D Facility, Continues Global Expansion to Deliver Medicines to More Patients Around the World. Press Release. July 23, 2024.

A new bioanalytical lab being opened by Ardena at the site is expected to be operational by the third quarter of 2025.

Ardena Acquires Catalent Drug Product Manufacturing Facility in New Jersey

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

Leroy (Lee) Hood, MD, PhD discusses the potential impact of precision medicine, moving towards a more preventive health model, and the role of AI in health information.

Lee Hood on Precision Medicine and Shifting Towards Prevention

Leroy (Lee) Hood, MD, PhD, has developed a long list of paradigm-shifting scientific instruments that have made possible major advances in the biological and medical sciences.

We had a chance to speak with Hood at the 

 World Conference in Santa Clara, CA, where he discussed the practicalities of turning a disease care system into a health maintenance system and also his plans to develop a new peptide information-based pharmaceutical company.

"Data-driven health is at an enormous turning point, and it's going to trigger, I think, within less than a five-year period, the ability to analyze literally millions of people with regard to their genome and [transcriptome], and from that derive the optimization of wellness, healthy aging, and even the ability to detect and reverse diseases early,” Hood told 

Hood went on to talk about the real-world adoption of preventive medicine versus treatment of chronic disease, suggesting that uptake will likely need to come from an economic point-of-view, given that there would potentially be an enormous amount of savings by avoiding chronic disease.

Hood is president and co-founder of the Institute for Systems Biology. He is also senior vice president and chief science officer of Providence St. Joseph Health. He is one of only 15 individuals elected to all three US National Academies—the National Academy of Science, the National Academy of Engineering, and the National Academy of Medicine. Hood played a key role in founding or co-founding 15 different biotechnology companies, including Amgen, Applied Biosystems, Rosetta, and Arivale. Hood was the recipient of the 1987 Albert Lasker Basic Medical Research Award for translating the genetics of antibody diversity into explicit molecular terms.

Hood, a pioneer of systems biology and systems medicine, shared his personal interest in starting a new peptide-based, informational-driven pharmaceutical company that would address wellness and longevity.

Systems Biology Pioneer Lee Hood Talks Precision Medicine, AI in Health, and the Next Paradigm Shift 

 is senior director, Business Development and Alliance Management, TPU (Tjoapack US).

The global biologics market is currently experiencing considerable growth, and it is set for even greater expansion in the near future. In 2022, the market was valued at $461.74 billion and is projected to reach $817.48 billion by 2032, growing at a compound annual growth rate (CAGR) of 8.5% (1). This growth is fueled by several factors, including an aging global population, increasing prevalence of chronic diseases, and advancements in biotechnology, including innovations in monoclonal antibodies and cell and gene therapies. In recent years, supportive regulatory frameworks in many countries have also helped accelerate the development and approval of biologics.

Current and future market trends in biologics packaging

The expansion of the biologics space has influenced growth in the packaging market, with continued innovation and favorable market conditions bound to propel this area’s further expansion. The following are some of the key trends driving this market:

 spoke with Mark Staiger, PhD, head of strategy at Schott Pharma, and Stefan Verheyden, global vice president, sales, pharma & biopharma solutions—injectables at Gerresheimer, about the outlook for pharma packaging in 2025.

What drug modalities is the market most focused on?

 The market is heavily focusing on GLP-1 agonists, [messenger] RNA-based drugs, and antibody-drug conjugates (ADCs). Significant investment and development are also seen in cell and gene therapies, CAR-Ts [chimeric antigen receptor T-cell therapies], and RNA [interference]. Personalized medicines are gaining traction, with companies like BioNTech making substantial progress.

 Almost half of newly approved drugs by FDA, EMA [European Medicines Agency] or other regulatory authorities are biologics. Depending on the therapeutic area and the route of administration, biologic drugs present several challenges to effective delivery, including the potential for elevated viscosity with increased concentration, larger volumes, and the sensitive nature of the biomolecules. The pharmaceutical primary packaging and the respective drug delivery devices must address these challenges and ensure drug stability through storage and transport as well as safe, precise drug delivery with patients’ comfort in mind. Our biologics customers often require smaller batch sizes and packaging solutions matching their high-end requirements, de-risking of fill/finish operations, and a significantly shortened time-to-market—all that, while ensuring patients’ safety.

What innovations or trends are you following when it comes to delivery formats?

 Finding new, innovative routes of administration with patients’ comfort in mind is an ongoing topic in the pharma industry. For the majority of our biologic customers, we still see injectables as the preferred route of administration. A clear trend toward drug delivery devices that enable home treatment, such as pens, auto-injectors, or on-body drug delivery devices is therefore noticeable.

 There is a noticeable shift toward subcutaneous administration, including large-volume injections, and ready-to-use (RTU) manufacturing. The number of biologics is steadily increasing, necessitating injectable formats. There is a continuous rise in demand for prefillable syringes (PFS), with a shift from vials to PFS and new approvals driving this trend.

Pharma companies seem to be transforming when it comes to packaging. What trends have you observed in areas including automation, smart packaging, regulatory compliance, and maintaining sterility?

 We see a clear trend in the industry toward deploying RTU or what Gerresheimer calls ‘ready-to-fill’ (RTF) formats in vials and cartridges, as we did some years ago with syringes. RTU/RTF packaging, like any pharmaceutical packaging, must meet rigorous standards. Pharma companies can mitigate the risk of contamination, maintain the highest quality, and thus ensure patient safety when deploying RTU/RTF packaging. And they can rely on robust validation and seamless regulatory approval of the primary packaging through comprehensive documentation and data packages. Industrialization at scale and highly automated processes are very important aspects for the whole industry. This includes primary packing and drug delivery systems like Gerresheimer is offering today. We have been using artificial intelligence (AI) technology in our own Gx G3 inspection systems for quality control for a number of years already, and we are constantly upgrading our automation and smart factory capabilities. Connected ‘smart’ packaging is certainly a very interesting trend in the industry and Gerresheimer offers a number of innovative solutions in this field.

 Automation is enhancing efficiency and reducing human error in packaging processes. Maintaining sterility is critical, especially with the rise of complex biologics and personalized medicines.

What major learnings from 2024 are going to help shape the year ahead?

 The rise of biologics will drive change in the industry. Beside the big pharma players, there are now a number of new, smaller players in the market with highly sophisticated drugs in the pipeline. We have one of the broadest portfolios in the industry: containment solutions in glass and plastics, as well as drug delivery devices, including our own intellectual property (IP) devices. And we amended our portfolio even further with the acquisition of Bormioli Pharma.

 The industry has learned the importance of supply chain resilience and localization to mitigate disruptions. There is a stronger emphasis on sustainability and eco-friendly packaging solutions. The need for digital transformation and data-driven decision-making has been highlighted, driving investments in AI and machine learning.

Increased demand for biosimilars and biobetters

. Biosimilars are expected to gain significant market share due to their lower cost than original biologics. The biosimilar market in the United States has experienced rapid growth, with 61 biosimilars approved across 17 unique biological molecules as of September 2024, and the global biosimilar market is estimated to reach $43.8 billion by the end of 2024 (2,3). Biobetters, which offer improved efficacy or safety profiles compared to original treatments, are also emerging as a promising trend. The biobetters market worldwide was valued at $65.7 billion in 2024 and is projected to reach $113.78 billion by 2031, growing at a CAGR of 8.2% (4). This rising demand is driving the need for specialized packaging solutions that ensure the stability of these products so that their efficacy is protected. By collaborating with experienced packaging partners, biosimilar and biobetter developers can leverage packaging as a strategic tool to enhance product differentiation, patient convenience, and overall success in this market.

. Advancements in genomics and proteomics are enabling the development of personalized biologics tailored to each patient’s genetic makeup. These treatments cater to niche patient groups with specific genetic or molecular markers, resulting in smaller batch sizes and increased complexity. Manufacturing and packaging need to adapt to handle smaller production runs efficiently, while logistics and supply chain management become more intricate due to diverse product variations. This is why these innovative therapies require flexible packaging and tailored solutions to accommodate diverse formats, fill volumes, and delivery devices to match specific patient needs. Packaging partners help biopharma companies use packaging as a strategic tool to support the successful development of personalized therapies.

Diversification of formulation approaches for a patient-centric approach

. Traditionally, biologics are often administered through injections, which can be inconvenient and painful for patients. To address this issue, researchers have been working on oral solid dosage (OSD) biologic formulations. They can be easily self-administered at home, eliminating the need for frequent visits to healthcare facilities for injections, saving time and reducing healthcare costs. Patients can take oral biologics anytime, anywhere, making integrating medication into their daily routines easier. OSD biologics can be designed with specialized delivery systems that protect the drug from degradation in the digestive system and enhance its absorption into the bloodstream. They can also be formulated for controlled release, delivering the medication gradually over time. This can lead to improved efficacy and reduced dosage frequency, helping minimize side effects and maintain a consistent therapeutic effect.
However, as the digestive system is a hostile environment for many biologics, not all are suitable for oral delivery. For those formulations, pre-filled syringes (PFS) and autoinjectors offer a user-friendly, safe, and convenient way of administration.

. The development of PFS and autoinjectors has simplified the injection process, making it easier for patients to self-administer biologics at home. Autoinjectors are designed for intuitive use, often requiring a single step to deliver the medication. This eliminates the complexity of traditional injections, which involve multiple steps like preparing the syringe, measuring the dose, and administering the injections. Autoinjectors feature ergonomic designs and clear instructions, making them easy to handle and operate, even for patients with limited dexterity or those unfamiliar with injections. The needle is hidden from view, and the injection is automated, which eliminates hesitation and anticipation that can contribute to needle-related anxiety and fear for patients uncomfortable with needles. Autoinjectors empower patients to self-administer their medication at home, reducing reliance on healthcare professionals and increasing independence.

Biologics development and packaging challenges and strategies

The complex nature of biologics, especially in OSD forms, PFS, and autoinjectors, presents unique challenges in their development, packaging, distribution, and delivery. Thankfully, ongoing innovations pave the way for more cost-effective production and patient-friendly administration, helping overcome these hurdles:

Biologics must remain stable during transport and storage, which is challenging due to their sensitivity to temperature, humidity, and light. Using materials with improved barrier properties, compatibility, and stability can enhance biologics’ performance and shelf life.

As PFS and autoinjectors require piercing the skin and bypassing the body’s natural defense systems, they must remain sterile right up to the point of administration to safeguard patient health.

Delivery systems face the same patient safety risks as other drug formats, especially regarding counterfeiting and tampering. Counterfeit drugs pose a danger to patients and undermine the security of the entire pharmaceutical supply chain. Regulations are in place to combat these threats, and packaging must adhere to these standards.

This is where secondary packaging comes in, providing additional protection and maximizing patient safety. In addition to aesthetics and helping with storage and transportation needs, secondary packaging helps preserve medicine integrity, enhance user convenience, and promote compliance and adherence. The right secondary packaging can include extra items like alcohol swabs, replacement needles, and clear instructions, making the process smoother for patients. With more people self-administering medications at home, child-resistant packaging becomes crucial to prevent accidental exposure and protect vulnerable patient groups, such as children or people with additional needs. Packaging partners, such as contract packaging organizations (CPOs) offering comprehensive services encompassing every aspect of the packaging process, can help ensure that biologics are safe and effective when administered.

Cost-effective biologics packaging solutions

The complexity of production and need for specialized facilities and equipment contribute to the current high cost of biologics. Working with a specialist CPO with experience in biologics offers advantages especially with diverse delivery methods. Specialized CPOs have expertise and infrastructure to handle biologics with care, ensuring integrity and efficacy. They can provide packaging solutions for biologics like pre-filled syringes, vials, and autoinjectors with appropriate temperature control and protection measures. CPOs are also well-versed in regulatory requirements and have established quality systems to ensure compliance, reducing risk of regulatory hurdles or delays. They can provide comprehensive validation documentation and support for packaging processes to ensure traceability and accountability.

Specialist CPOs also tend to stay abreast of all of the latest innovations in biologics packaging, such as drug delivery systems, and connected packaging technologies. Leveraging the knowledge of partners with expertise in innovative solutions can significantly reduce the cost of life-saving biologics, making them more accessible to healthcare systems as well as patients.

 (2022 to 2032). FMI–Future Market Insights, October 2022.
2. Samsung Bioepis. 

; 7th edition; Samsung Bioepis, September 2024.
3. Jha, S. N. 

(2024 to 2034). Fact.MR, June 2024.
4. Persistence Market Research. 

, Share, and Growth Forecast for 2024–2031. Persistence Market Research, September 2024.

Joe Compton is senior director, Business Development and Alliance Management, TPU (Tjoapack US).

®
Vol. 49, No. 1
January/February 2025
Pages: 23–25

When referring to this article, please cite it as Compton, J. Meeting Secondary Packaging Challenges of Innovative Delivery Systems for Biologics. 

Rapid market growth in biologics is helping the packaging market expand as well, but the complex nature of biologics and the desire for personalized therapies present unique hurdles to make packaging solutions cost-effective and safe for patients.

Meeting Secondary Packaging Challenges of Innovative Delivery Systems for Biologics

Demand for biosimilars is predicted to be expanding at a compound annual growth rate of nearly 18% from $9.4 billion in 2023 to $66.9 billion in 2028 (1). This strong growth reflects both higher acceptance and adoption rates and increasing numbers of approvals in multiple regions. By mid-2024, 40 biosimilars had been approved by FDA in the United States, with 25 products launched to the market. While this growth is attracting new entrants, hurdles to developing cost-effective and competitive biosimilars remain. In addition to the need to clearly demonstrate biosimilarity to reference branded products, manufacturing complexity, including scaling challenges, must be overcome.

Developing a biosimilar starts with characterization of the reference product. That information is used to develop a cell line capable of producing the desired product with comparable post-translational modifications and other important product quality attributes. Process development and optimization, including upstream cell culture and downstream purification comes next. Comprehensive product characterization, formulation development, fill/finish, final product release, and packaging round out the activities.

Process consistency and robustness, analytical excellence, and regulatory compliance are essential in the scale-up of biosimilars.

Featured Content

Drug Solutions Podcast:

Out-of-the-Box Packaging Advancements

Drug Digest:

Ask the Expert