Pharmaceutical Technology Is Now PharmTech: A Sharper Name for a Smarter Industry

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Behind the Headlines Episode 28

Ask the Expert

Closing the Gap in Modern Process Control and Automation for QC/QA

Drug Digest December 2025

How It Helps Avoid Facility and Equipment Problems

A “Plan, Prevent, Prove” Approach

Cheryl Barton is director of PharmaVision, 

Creative background, the human brain on a blue background, the hemisphere is responsible for logic, and responsible for creativity. different hemispheres of the brain, 3D illustration, 3D render | Image Credit: © Aliaksandr Marko - Stock.adobe.com

The global central nervous system (CNS) therapeutics market is forecast to increase from US$80.25 (€74.7 billion) in 2023 to US$106.19 billion (€98.78 billion) by 2031, growing at a compound annual rate of 4.8%. This market growth can be attributed to a few drivers, including the fact that biopharma companies, such as AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo Co, Eisai, Lundbeck, Merck & Co., Novartis, Pfizer, Roche, and Takeda, are all targeting hard-to-treat neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) (1).

Numerous disease-modifying biologics are in late clinical development for treating neurodegenerative diseases (

 [2]), and several brain-penetrant monoclonal antibodies (mAbs) have recently been approved for treating AD. In 2021, the US Food and Drug Administration (FDA) approved Biogen and Eisai’s aducanumab (Aduhelm), the first amyloid beta-directed antibody to reach the market for the treatment of AD (3). However, the clinical results were mixed, and the developers withdrew the European Medicine Agency (EMA) marketing application in April 2022. Aducanumab has also been withdrawn from the US market as a result of low uptake and payor challenges. Aducanumab appears to disrupt the blood–brain barrier (BBB) to have a marginal impact on amyloid plaque formation (4).

Disease modifying biologics under clinical development for Alzheimer’s disease (AD) and Parkinson’s disease (PD).

In the meantime, Biogen/Eisai received FDA approval for lecanemab (Leqembi), in the US in January 2023, and EMA is expected to review the marketing authorization application shortly (5). Leqembi is making steady inroads within the US Alzheimer’s community, and the partners are now working on a subcutaneous formulation to ease use and drive uptake. Now the race is on to see who can develop the next biologic to treat AD or the elusive PD; to do this they will need to use the latest CNS delivery technology to ensure targeted delivery and durable responses.

CNS drug development remains challenging and is associated with high costs and high failure rates, largely due to the difficulties associated with getting drugs across the BBB (6). A host of biomaterials have been designed to bypass or facilitate the passage of small molecules across the BBB including passive transcytosis, conjugate ligands, membrane coating (e.g., erythrocytes, macrophages, neutrophils), liposomal and polymeric nanoparticles, micelles and nanogels, and stimuli-triggered BBB disruption (e.g., electroacupuncture, light, ultrasound) (

). However, the systemic delivery of biopharmaceuticals such as gene therapies, mAbs, and enzyme replacement therapies has remained off-limits as they cannot cross the BBB, so companies have relied on intrathecal or intracranial injections to deliver these therapeutics to the site of action (7). But things are about to change.

Novel approaches to central nervous system drug delivery.

Biopharma companies have begun to develop novel approaches using neurotropic viruses and receptor-mediated transcytosis or “peptide shuttles” to deliver biologics into the brain (8,9). For example, Spain-based Gate2Brain (G2B) has developed peptide shuttles that co-opt receptor mediated transcytosis pathways to transport therapeutic cargo into the brain (10). Conversely, VectorY Therapeutics has taken a novel approach combining antibodies with adeno-associated virus (AAV) capsids to form vectorized antibodies to selectively target the CNS and treat neurodegenerative diseases (11).

G2B novel peptide shuttles to treat glioblastomas

G2B was established in 2020 by CEO, Meritxell Teixidó to exploit delivery technology that was developed at IRB Barcelona. The biotech company focuses on developing innovative non-antigenic, protease-resistant, peptide shuttle conjugates that can penetrate the BBB to deliver antibodies, DNA/RNA, proteins, and small molecules through receptor-mediated transcytosis. It is currently developing G2B-002, with its lead drugs, and is planning to conduct studies with G2B-002 in the treatment of a rare paediatric cancer, diffuse intrinsic pontine glioma (DIPG) (10).

In 2021, G2B was granted financial support from DTI, the Center for Industrial Technological Development, Ministry of Science and Innovation, within the framework of the Neotec projects (12). In December 2022, G2B received €2.5 million in funding to develop its drug delivery technology to target brain cancers. These funds will enable the company to drive the clinical development of G2B-002 over the next few years (13).

But competition in this field is increasing. US-based Denali Therapeutics has also developed transferrin-mediated peptide shuttles to efficiently transport small molecules and biologics drugs to the brain to restore lysosomal function, glial biology, and cellular homeostasis in a variety of rare diseases (14). Denali will begin a Phase I/II clinical trial testing DNL310 (ETV:IDS) in children with Hunter syndrome and plans to expand this technology beyond enzymes and therapeutic antibodies to transport anti-sense oligonucleotides.

Meanwhile, Roche has developed its own transferrin-mediated peptide shuttle delivery technology which it has deployed in its Aβ-immunotherapy gantenerumab. Unfortunately, this antibody failed to show a decline in AD in Phase II clinical trials despite being brain penetrant (15,16).

VectorY Therapeutics next-generation gene therapies

VectorY Therapeutics was established in October 2020 at the Amsterdam Science Park in The Netherlands. The biotech company focuses on the development of innovative gene therapy approaches for the treatment of muscular and neurodegenerative disorders through vectorized antibodies. These non-immunogenic viral vectors enhance the properties of cell type specificity, to improve the delivery, durability, and accessibility of targeted tissues and cells. The company has developed three proprietary delivery technologies:

—an AAV vector that delivers the VecTab transgene (a pathogenic protein) to the neuron where the therapeutic antibody (VecTab) is subsequently produced. The therapeutic antibody binds to disease-associated lipids and proteins to modify the disease.

—a vectorized antibody fused with a degron sequence that directs the target toward pathway-specific degradation. The AAV delivers the VecTron transgene to the neuron where the therapeutic antibody-degron fusion protein (VecTron) is produced and leads to pathway-specific protein degradation.

—tissue-specific recombinant AAV capsids which are optimized for efficient delivery of antibodies intracellularly in the CNS.

—VecTab vectorized antibody programme targeting TDP-43 for the treatment of amyotrophic lateral sclerosis (ALS)

—VecTab/VecTron vectorized antibody targeting misfolded and aggregated huntingtin (HTT) proteins for the treatment of Huntington’s disease (HD)

—VecTab/VecTron vectorized antibody targeting alpha-synuclein for the treatment of PD (17).

On 15 June 2021, VectorY completed a €31 million seed financing round. The oversubscribed round was co-led by founding investors Forbion, BGV, and Eli Lilly & Company (18). In October 2023, VectorY raised €119 million (US $138 million) in a Series A financing round to advance its vectorized antibody programmes in neurodegenerative diseases. The round was co-led by EQT Life Sciences and the Forbion Growth Opportunities Fund and included existing investors MRL Ventures Fund (a corporate venture arm of Merck & Co.) Insight Partners, ALS Investment Fund, Forbion Ventures, BioGeneration Ventures (BGV), and others (19).

Several other companies are looking to use AVV to vectorize antibodies, including US-based Voyager Therapeutics which teamed up with AbbVie on the development of tau and alpha-synuclein vectorized antibodies to treat AD and PD, respectively. AbbVie later terminated the agreement due to a change in pipeline strategies (20). Voyager recently partnered with Neurocrine Biosciences to develop a candidate for the GBA1 gene programme to treat PD utilizing its intravenously administered, BBB penetrant, novel capsid derived from Voyager’s TRACER capsid discovery platform (21).

Challenges and future opportunities in CNS drug delivery

Introducing disease-modifying biologics into the brain poses a unique set of challenges compared to other body tissues due to the protective mechanisms of the BBB. However, new delivery technologies such as G2B’s peptide shuttles and VectorY’s vectorized antibodies demonstrate that these challenges can be overcome, and now it is down to pharma to identify the most appropriate therapeutic targets to pursue. Whether that’s anti-amyloid or anti-tau mAbs for the treatment of AD or alpha-synuclein-targeting gene therapies for PD, a new era of CNS biopharmaceuticals awaits.

1. Precision Reports. CNS Therapeutics Market Size in 2024: Increasing Technological Advancements by Top Key Players to 2031. 6 March 2024.
2. ALZFORUM, Therapeutics. Accessed 1 April 2024.
3. Glymour, M.M.; Weuve, J.; Dufouil, C.; Mayeda, E.R. Aduhelm, the Newly Approved Medication for Alzheimer Disease: What Epidemiologists Can Learn and What Epidemiology Can Offer. 

, 191 (8), 1347-1351.
4. Haddad, H.W.; Malone, G.W.; Comardelle, N.J.; et al. Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer’s Disease: A comprehensive review. 

, 10 (3), 37023.
5. Biogen. FDA Approves LEQEMBI™ (lecanemab-irmb) Under the Accelerated Approval Pathway for the Treatment of Alzheimer’s Disease. News release, 6 Jan. 2023.
6. Nance, E.; Pun, S.H.; Saigal, R.; et al.Drug Delivery to the Central Nervous System. 

, 7, 314–331.
7. Wu, D.; Chen, Q.; Chen, X.; et al. The Blood-Brain Barrier: Structure, Regulation, and Drug Delivery. 

, 8, 217.
8. Terstappen, G.C.; Meyer, A.H.; Bell, R.D.; et al. Strategies for Delivering Therapeutics Across the Blood-Brain Barrier. 

, 20, 362–383.
9. Sheridan, C. Drugs Catch a Ride Through the Blood-Brain Barrier. 

, 41, 1182–1184.
10. Gate2Brain. Pipeline & Therapeutic Proof of Concept. Accessed 1 May 2024.
11. VectorY Therapeutics. Efficient Intracellular Therapeutic Antibodies. VectorY Platform. Accessed 1 May 2024.
12. Gate2brain, Gate2Brain has been granted financial support by the CDTI. News release, 22 Dec. 2021.
13. Gate2brain. Gate2brain Receives €2.5m Funding to Develop a Technology that Enhances Drug Delivery to the Brain. News release, 21 Dec. 2022.
14. Denali Therapeutics. Pipeline. Accessed 1 May 2024.
15. ALZFORUM. Molecular Transport Vehicle Shuttles Therapies into Brain. 29 May 2020.
16. Alzheimer Research, UK. Alzheimer’s Drug Gantenerumab Fails to Slow Decline in Phase III Clinical Trials. 14 Nov. 2022.
17. Konstantinova, P. Precision Targeted Therapies for Neurodegenerative Diseases. DHDRN Presentation. 23 Jan. 2023.
18. VectorY Therapeutics. VectorY Raises €31 million in Seed Financing to Develop Next-Generation Gene Therapies Aimed at Muscular and CNS Disorders. News release. 15 June 2021.
19. VectorY. VectorY Raises €129 Million ($138 Million) Series A Financing to Advance Vectorized Antibody Programs in Neurodegenerative Diseases. News release, 13 Nov. 2023.
20. Voyager Therapeutics. Voyager Therapeutics Provides Update on AbbVie Vectorized Antibody Collaborations. News release, 3 Aug. 2020.
21. Voyager Therapeutics. Voyager Therapeutics Announces Selection of Development Candidate for GBA1 Program in Collaboration with Neurocrine Biosciences, Triggering Milestone Payment. News release, 16 April 2024.

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

When referring to this article, please cite it as Barton, C. Frontrunners in CNS Drug Delivery. 

Articles

Novel delivery technologies enhance brain penetration to target neurodegenerative diseases and glioblastomas.

Frontrunners in CNS Drug Delivery

Feliza Mirasol is the science editor for 

US-headquartered ProPharma, a US-headquartered provider of regulatory, clinical, and compliance services for the life sciences industry and a portfolio company of Odyssey Investment Partners, and Italy-based PBL, a custom solutions provider to the pharmaceutical, chemical, and diagnostics industries have launched the Cell Factory Box (CF Box), an enclosed, fully automated cell factory device. The companies launched the device under a partnership. 

The CF Box enables the decentralized manufacturing of all types of cell and gene therapies (CGTs) in Class D (ISO8) or controlled not classified surrounding areas, according to a May 2, 2024 press release.

“Regarding treatment options, many are adopting a decentralized approach to manufacturing [CGTs],” said Eleonora Casucci, vice-president of Quality & Compliance EU, ProPharma, in the press release. “The CF Box provides key advantages compared to the devices currently available. Our collaboration with PBL positions us to serve those in the [CGT] segment fully.”

According to the release, the CF Box uses already-approved artificial intelligence (AI) technology and is extensively automated, allowing it to significantly reduce manual operation. The nature of the device also reduces the need for high-class clean rooms. Using approved AI technology, the CF Box employs batch detection recognition, which is set to a frozen state during validation, and batch manufacturing. Users can select modules based on individual needs and select the type of products/technologies desired. Additional modules can also be added at later stages.

“Robotic arms, cameras, liquid transfer systems, conveyor belts, components, and tools are available in the market, enabling full automation, including but not limited to alerting the operator once the culture has reached the desired values,” the press release states. The design allows for flexibility in automating manual processes and supports diverse manufacturing tasks. The CF Box is also programmable for various processes, including optimized cell culture expansion, and streamlining manufacturing timelines effectively, according to the release.

“We are honored to work with ProPharma on such a monumental effort,” said Filippo Begarani, Research and Innovation manager, PBL, in the press release. “Our first goal is always to conceive, design, and implement technologically advanced solutions with the highest standards of quality and innovation, and the CF Box device will not only change but elevate how [CGTs] are manufactured since it supports high reproducibility of the process at various locations.”

The CF Box will be demonstrated in Frankfurt, Germany, during ACHEMA, which will be held June 10–14, 2024. PBL is also offering demonstrations after the event and upon request at its facility in Parma, Italy.

The global CGT market size is projected to grow to $82.24 billion by 2032 from $15.46 billion in 2022, with a compound annual growth rate of 18.3% (1). Key market drivers are the exponential increase in the CGT clinical pipeline and an increase in the number of regulatory approvals for innovative medicines.

Cell and Gene Therapy Market (By Therapy Type: Cell Therapy and Gene Therapy; By Indication: Cardiovascular Disease, Cancer, Genetic Disorders, Infectious Diseases, Neurological Disorders; By Delivery Method: In-Vivo and Ex-Vivo; By End-Users: Hospitals, Cancer Care Centers, Wound Care Centers, Others)—Global Industry Analysis, Size, Share, Growth, Trends, Regional Outlook, and Forecast 2023-2032

ProPharm and PBL have introduced a fully automated, enclosed cell factory manufacturing device.

New Cell Factory Box Launched by ProPharma and PBL for Automated CGT Manufacturing 

In a new research collaboration and license agreement, Poseida Therapeutics and Astellas Pharma’s wholly owned subsidiary, Xyphos Biosciences,will develop novel 

CAR programs to target solid-tumor cancers.

Under the agreement, the companies plan to combine Poseida’s proprietary allogeneic chimeric antigen receptor T cell (CAR-T) platform with Xyphos’ ACCEL technology to create one Poseida-developed CAR-T construct. This construct is intended to serve as the basis of two 

CAR product candidates targeting solid tumors.

“We are excited to expand our relationship with Astellas, where we share a vision that cutting edge, off-the-shelf cell therapies can address significant unmet needs of patients with solid tumor malignancies. Today’s agreement further reinforces the economic value of Poseida’s highly differentiated non-viral technologies and enables development in areas beyond our core pipeline focus,” said Kristin Yarema, PhD, president and CEO of Poseida, in a May 1, 2024 company press release.

Under the transaction, Xyphos will reimburse Poseida for costs incurred as part of the research agreement. Xyphos will be responsible for the development and future commercialization of products generated from the collaboration. Poseida will receive a $50 million upfront payment as well as potential development and sales milestones and contingency payments that could total up to $550 million. Poseida is also eligible for up to low double digit tiered royalties as a percentage of net sales.

“At Astellas, we have a strong commitment to developing novel treatments for patients with cancer and have positioned immuno-oncology as a [p]rimary [f]ocus of our R&D strategy [1] … we are focused on reinvigorating the immune system’s ability to discover, disarm, and destroy cancers in more patients. By combining the ACCEL platform with Poseida’s elegant and cutting-edge genetic editing platforms, we believe the collaboration will bring synergies between the two companies’ breakthrough research and will ultimately lead to expansion of Astellas’ portfolio and to delivery of innovative CAR-T cell therapies to cancer patients,” said Adam Pearson, chief strategy officer of Astellas, in the press release.

Astellas is making a strategic investment in Poseida, which it announced in August 2023 (2). Under this transaction, Astellas is investing a total of $50 million, comprising $25 million to acquire 8,333,333 shares of Poseida common stock, a one-time $25 million payment for a right of exclusive negotiation and first refusal to license P-MUC1C-ALLO1, one of Poseida's clinical-stage programs. The candidate is an allogeneic CAR-T cell therapy being developed to treat multiple solid tumor indications. Also under this transaction, Astellas has been granted a board observer seat on Poseida’s board. The position includes the ability to attend Poseida’s scientific advisory board meetings as well as certain notice rights related to any potential change of control of Poseida.

 (accessed May 6, 2024).
2. Astellas Pharma. Astellas and Poseida Therapeutics Announce Strategic Investment to Support Poseida’s Commitment to Redefining Cancer Cell Therapy. Press Release, Aug. 8, 2023.

The two companies will combine their cell therapy platforms to develop convertibleCAR programs targeting solid tumors.

Poseida Therapeutics and Astellas to Develop Novel Allogeneic Cell Therapies

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 United States Federal Trade Commission (FTC) is seeking more information on Novo Nordisk parent’s $16.5 billion proposed acquisition of Catalent, a US-based contract development manufacturing organization (CDMO). Catalent stated on May 3, 2024 that both companies were gathering information in order to respond to the FTC’s request (1), which was received on May 2. This request was submitted weeks after an application to the FTC was refiled to approve the deal.

Novo Nordisk announced its decision to acquire Catalent in early February 2024 (2). Under a planned merger of Novo Holdings, the parent company of Novo Nordisk, and Catalent, Novo Nordisk would receive three of Catalent’s fill/finish sites and related assets. Those three sites, located in Anagni, Italy; Bloomington, Indiana (US); and Brussels, Belgium, would be advantageous for Novo Nordisk, which has been steadily increasing production of Wegovy as demand for the drug explodes.

Novo Nordisk emphasized its goals of expanding Wegovy production in its own press release on the acquisition (3). The deal would enable the company to expand manufacturing capacity while allowing flexibility for its existing supply network. “We are very pleased with the agreement to acquire the three Catalent manufacturing sites which will enable us to serve significantly more people living with diabetes and obesity in the future,” said Lars Fruergaard Jørgensen, president and chief executive officer, Novo Nordisk (2). “The acquisition complements the significant investments we are already doing in active pharmaceutical ingredients facilities, and the sites will provide strategic flexibility to our existing supply network.”

Demand for Wegovy, Novo Nordisk’s obesity and cardiovascular disease treatment, has skyrocketed over the last year, alongside its sister diabetes therapy, Ozempic. Wegovy was approved in the US in early March of 2024 to reduce risk of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal heart attack (myocardial infarction), or non-fatal stroke in either overweight or obese adults with established cardiovascular disease (CVD) (4). Novo Nordisk also filed for a label expansion in the European Union.

Both Novo Nordisk and Catalent still expect to close the deal by the end of 2024, but doubts were raised when Novo Nordisk refiled the application in April. According to a Reuters press release, David Ricks, CEO of Eli Lily, a major competitor to Novo Nordisk and Wegovy, raised potential antitrust concerns, calling Novo Nordisk’s proposal to buy the plants “unusual” (4). Novo Nordisk did not disclose details about why the application was refiled.

US SEC. Form 8-K. Current Report Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934, Catalent, Inc. May 3, 2024. https://www.sec.gov/Archives/edgar/data/1596783/000119312524129990/d797118ddefa14a.htm

Novo Holdings to Acquire Catalent in Deal Valued at $16.5 billion

Novo Nordisk to Acquire Three fill-finish Sites from Novo Holdings A/S in Connection with the Catalent, Inc. Transaction

Wegovy Approved in the US for Cardiovascular Risk Reduction in People with Overweight or Obesity and Established Cardiovascular Disease

US FTC Seeks More Information on Novo Nordisk Parent-Catalent Deal

The request for more information was received weeks after an application to the FTC was refiled to approve the deal.

US Federal Trade Commission Seeks Additional Information on Novo Nordisk Parent-Catalent Deal

Data are the biopharma industry’s most valuable asset today, which is prompting the industry to step up its measures to not only gather these data, but to protect them as well. In a conversation with Nathalie Batoux, product manager, Research Innovation, IDBS, 

 delved into the approaches the biopharma industry has taken to shore up data integrity protection. 

Editor's note: this article was published in the Pharmaceutical Technology Europe May 2024 issue.

 Explain why data are the biopharma industry’s most valuable asset. The analogy is that there’s a gold rush for data (1); what does that mean?

 With the current digital transformation happening in the biopharma industry, the industry has also seen the explosion of [tools such as] artificial intelligence (AI) and machine learning (ML). There is also a significant amount of data that exists now based on the products already on the market. With the explosion of AI and ML, people want to reuse the data that they have. So, instead of running new experiments, already existing data are being used; these historical data are very important. There are some new initiatives underway to review and repurpose existing drugs for other applications, thus, AI and ML are being used to review these already existing data. Not only is the biopharma industry producing a vast amount of new data, it also has its hands on a significant amount of historical data.

 Describe the impact of this perception—this ‘gold rush’ for data—on data integrity. Has it led to a flurry of activity?

Yes, there is a flurry of activity. There are many startups that are proposing AI and ML to the biopharma industry, amongst other industries. There are initiatives, as I mentioned, around the repurposing of existing drugs using historical data at hand.

 Can you discuss where data integrity practices in the biopharma industry are the strongest and where they are the weakest?

 My perspective is to look at the evolution within the industry, and where we are now with digitalization, data integrity is getting much stronger. Looking at the practice of manually recording, or manually transcribing, data from one system to another, this is very much error prone. Whether intentionally or accidentally, errors are highly likely. If there is an error in the data, then any analysis conducted later on will be incorrect, and the decision-making using that data will not be good and will thus be counterproductive. This will cost money at the end of the day.

Good data integrity involves the use of more automated systems, using digital transformation where the system records the context around the results. For example, in an experiment, scientists—even though they are very well trained—are still human. There’s only a finite number of parameters that they can deal with. While a computer, or a series of computers, can record all sorts of things around the context. It’s as simple as the date and time of an experiment that might change the outcome, whether [the experiment] is done in the summer or winter. That is important as temperature and humidity conditions may affect the outcome.

The other advantage is that, with data digitally recorded, there is traceability, and most of the modern systems now have audit capabilities. [This makes it easier] to understand what has happened to generate that data, but also what has happened after the data has been generated—such as, has the data been transferred from one system to another? Having all that context, having this history, ensures that, in the first place, the data—that is, the data that will be used to train the models for ML or analysis, or for use by AI—will be of quality. [And that assurance comes from] all that context, all that history behind the data.

Data that are digitally recorded [are] easier to find. [In the laboratory], finding an experiment on paper or in a notebook is not easy. [Digitally recorded data] offer interoperability and [better] accessibility. If [the data are] on paper, for example, [the lab tech] needs to have that piece of paper in front of [them] to be able to see it. This hinders interoperability [because] that piece of paper, if the handwriting is, as they say, like a doctor’s handwriting, not many people will be able to understand it. Being ‘reusable’ as a whole is very, very important for data, so having FAIR [findable, accessible, interoperable, and reusable] data is one of the principles of data integrity. This will enable the digital transformation and all those initiatives that are happening with ML and AI.

 Let’s talk about the data itself. Good data versus bad data; how is that determined?

 As mentioned earlier, having all the context around the data recorded is one of the attributes of good data. The other attributes, as I mentioned, are the FAIR principles; however, one needs to make sure that they are recording everything. It’s human nature to try to record things that are happening and [what is] working, but from a learning perspective—and for ML, in particular—one needs to also record what didn’t work because [there is] much more to learn from things that didn’t work. So, the ‘how to’ recognize good data versus bad data requires having rigour, using well documented SOPs [standard operating procedures], and having controls in place, all of which are quite important because these help with the reproducibility of that data.

In addition, if using a digital system with controls in place, then [the technician] will receive an alert, and [this allows] them to record an exception. It is very important to record all those things, not only for good data in general, but also for the data that regulatory bodies require. [Keep in mind], all the compliance requirements are very important. Another point [to highlight] is that for accessibility and interoperability, more than one system will need to be used; likely, it will require several systems. And, data needs to be connected easily, so having silos that are not talking to each other, that don’t represent each other, that is not good data. Having the ability to connect the data—to connect to the structure of that data in order to understand them—that is a symptom of good data.

 How is the biopharma industry handling this flow of data; how is it preparing for this gold rush that was mentioned earlier?

 [With the] digitalization that is happening, less companies are using paper, and [it seems that] more and more companies have been investing in data scientists to be able to mine the data. However, there is a difference between having all that data mined by specialists and the people who are actually using the data at the bench, so having democratization of data is extremely important. Empowering [bench] scientists with decision-making based on large data sets, including past data, at the click of a button is very valuable. Rather than having to wait for a few weeks for data scientists’ analyses—although the data scientists’ skills are still important for more complex analyses—a more diverse set of scientists or end users can have accessibility to data with [the goal] of helping to put algorithms in place for the analyses, and so on.

1. Batoux, N.; Rayner, D. In a Digital Gold Rush, Data Integrity is Priceless. 

®
Vol. 36, No. 5
May 2024
Pages: 33–34

When referring to this article, please cite it as Mirasol, F. Shoring Up Data Integrity Practices. 

Digital transformation is allowing for better handling, analysis, and protection of vast data collection.

Shoring Up Data Integrity Practices

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

Young woman giving pill to her daughter at table | Image Credit: ©Pixel-Shot - stock.adobe.com

Taking patient needs and expectations into consideration when designing and developing new drugs has become increasingly important as evidence mounts that more convenient and easier-to-take products increase medication compliance. To be effective, drug therapies require patient adherence. For oral dosage drugs, particularly liquids, dispersible powders (granules), orally disintegrating tablets or films, chewable tablets, and minitablets, taste-masking can be critical for increasing patient compliance, as these dosage forms result in exposure of taste buds to the APIs, which can be an unpleasant experience, according to Liliana Miinea, technology manager, Pharmaceutical Excipients, at Lubrizol Life Science.

Leveraging taste-masking technologies and solutions that impart an attractive appearance help overcome such issues. It is a complex task, however, that requires consideration of numerous variables including patient profiles, drug product characteristics, and regulatory rules, among others, observes Nasrin Mahmoudi, Sr., lead applications scientist at IFF Pharma Solutions. As such, expertise in these formulation technologies is essential to implementing a patient-centered approach to drug development and ultimately improved therapy outcomes.

Important factors influencing patient compliance

With respect to factors influencing patient compliance, most experts agree that taste and appearance are two of the most important. For oral administration, they may only fall below ease of swallowing and dosing frequency, says Steve Amoussou-Guenou, technical development manager Europe at Roquette.

In addition to palatability and swallowability, other attributes that help ensure patients follow medication regimens as recommended and without delays, skips, or increasing/lowering the dose include acceptable aroma/smell and product packaging, adds Mahmoudi. “In 2006, the [European Medicines Agency] (EMA) reported that taste, smell, and texture were all integral factors in determining a medication’s acceptability for patients,” she says (1).

Excipients that can be used to taste-mask bitter APIs are referred to as bitter blockers. These compounds inhibit the molecular pathway that ultimately results in a bitter taste in the mouth on the cellular level (1). Compounds that block bitter receptors could potentially be used as excipients and replace other more complex taste-masking technologies.

Bitter tastes are detected by G-protein coupled receptors (GPCRs), predominantly those in the taste 2 receptor family (TAS2R), which comprises approximately 25 GPCRs (1). Molecules that preferentially bind to these receptors can prevent the detection of bitter tastes. However, genetics has a role to play in how each person perceives bitterness. In fact, more than 150 single-nucleotide polymorphisms have been found in TAS2R coding regions, all of which can influence the sensitivity of an individual to bitter tastes.

Another challenge is the need to identify which taste receptor(s) are targeted by a given API, as the bitter blocker must target the same receptor(s) to be effective (1). Often multiple receptors are involved, and therefore, a single bitter blocker will need to bind to most of them to truly block, rather than simply reduce, the perceived bitterness of an API.

1. Andrews, D.; Salunke, S.; Cram, A.; et al. Bitter-Blockers as a Taste Masking Strategy: A Systematic Review Towards Their Utility in Pharmaceuticals. 

“The importance of taste masking can be attributed to the fact that many APIs can be unpleasant or even impossible to consume without an effective taste-masking strategy—literally the spoonful of sugar that helps the medicine go down,” Amoussou-Guenou says.

Appearance, meanwhile, can be viewed by patients as an indication of quality. In certain markets such as Japan, Amoussou-Guenou notes, even a slight visual defect such as black specs or color heterogeneity will immediately cause concern. A consistent appearance is therefore vital for securing patient trust, as well as their attention. Some drug companies also use a unique visual appearance as a marketing tool and/or to help consumers identify their medications, limit cross contamination, and avoid potential toxicity.

Taking a patient-centric approach to formulation design

The most effective strategy for developing patient-centric formulations and achieving higher levels of medication adherence is to adopt a patient-centric design approach from the outset, Mahmoudi contends.

“Understanding how patient needs and preferences are influenced by variables such as age, overall health, disease states, and physical condition can help to design a patient-centric drug product suitable for a target patient population,” she explains.

For oral formulations, Mahmoudi says, tablet size, shape, smell, taste, and mouthfeel—or, for liquid dosages forms, rheology and volume as well as smell and taste—all impact a drug’s overall acceptability because they all impact swallowability.

To identify the needs of the target population, formulators rely on experience, sensory analysis, and marketing studies, according to Amoussou-Guenou. “[These] data are used alongside other factors like the dosage form type and advice of marketing teams to inform decisions around the drug product’s appearance and desired properties, as well as the most effective taste-masking technique to employ,” she comments.

The dosage form can also be an important dictator of taste-masking requirements. Orally disintegrating tablets (ODTs) and films (ODFs) are good examples, according to Amoussou-Guenou. “These dosage forms are specifically designed to dissolve in the mouth, and their buccal dissolution profile makes taste masking an especially important consideration,” he explains. In these applications, Amoussou-Guenou says producers typically opt for the functional excipient route, rather than coatings, though complexing the API is a viable secondary measure. Multipurpose, co-processed excipients that impart multiple attributes to ODT/ODF formulations are often preferred, as they can support rapid disintegration as well as a pleasant mouthfeel and flavor.

Several different approaches to taste-masking provide formulators with options depending on the various factors in play. The main determinant is the extent and type of the unpleasant taste or smell of the drug, whether it is bitter, sour, or an irritant, according to Mahmoudi. An API’s aqueous solubility also plays an important role in selecting a taste-masking technique because it can be more challenging to cover the poor taste of highly water-soluble drug substances. It is also often easier to taste-mask low dose formulations. In addition, the particle size and shape and the texture of the API, as well as the target release profile, should be considered when selecting a taste-masking method, Mahmoudi says.

The API can be chemically modified into a salt or pro-drug form to reduce its bitterness, according to Amoussou-Guenou. This technique is limited, however, to drug substances with suitable functional properties. More commonly, excipients with a sweetening effect are added to hide the bitter/unpleasant taste of the API. Molecular complexation with compounds such as cyclodextrins can also mask the taste of the API while the drug resides in the mouth. Finally, application of a barrier coating that remains intact while in the mouth but degrades once exposed to the acidic conditions in the stomach is another widely used approach.

“If an API is only bland or mildly off-putting, formulators can simply add acids, flavorants, or sweeteners to combat the bitterness. Excipients with a naturally sweet flavor, like mannitol, are common here, as they combine good tabletability with effective taste-masking characteristics,” Amoussou-Guenou notes.Coatings are preferred if the API has a strong bitter taste that cannot be sufficiently masked with the addition of excipients to the formulation.

Formulations can also combine taste-masking techniques in the case of particularly unpleasant-tasting APIs. When formulating ODTs for example, Amoussou-Guenou observes that the API can first be complexed with cyclodextrins, hiding the bitter compounds from the patient’s taste buds. Then the complexed API can be combined with a high-performance mannitol to lend reduced friability and a better overall tablet consistency, as well as a cool, almost minty taste that makes the disintegrating tablet a pleasure to take.

With respect to polymer coating technologies used for taste masking, Mahmoudi notes there are several hydrophobic or hydrophilic polymers and lipidic compounds available that can be used as coating materials. She highlights ethyl cellulose as a hydrophobic polymer with a pH-independent release. Mahmoudi also notes that the coating level will be determined by the bitterness level of the API and the dosage form properties and can be adjusted to not only provide taste masking, but also control the API release profile.

Miinea emphasizes how taste-masking technologies are continuously evolving to align with the progress in novel oral dosage forms that address the needs for patients with difficulty in swallowing. She points to polymethacrylates as being increasingly used as barrier coatings to taste-mask bitter APIs. Miinea specifically notes that crosslinked polyacrylic acid polymers (carbomers) having structures similar to weak cation exchange resins may form complexes with weakly basic drugs. “The resultant complexes are insoluble in saliva and mask the bitter taste of the API. When they reach the stomach and are exposed to its low-pH environment, they ionize and release the API without impacting its bioavailability. These polymers may also provide additional functionality, including reduced ‘throat catch,’ or the burning sensation associated with some APIs, including ibuprofen,” she remarks.

Meeting the needs of specific patient populations

Patient-centric formulation requires consideration of the close connections between user needs, dosage form design, and taste-masking technologies, because each patient population has its own discrete preferences and priorities, making some delivery methods more-or-less suitable, Amoussou-Guenou observes. In turn, he notes that just as the choice of delivery method stems from patients’ needs, taste-masking technologies are influenced by a drug’s format and target application.

In particular, Amoussou-Guenou notes that for groups with specialized needs such as pediatric, geriatric, and psychiatric patients, it may be necessary for drug developers to “think outside the pill box” to ensure taste-masking methods remain effective. For instance, some medications prescribed to children are not manufactured in pediatric dosage levels. For tablets, breakage in half or smaller units is therefore required. Barrier coatings used for taste masking will not be effective in this case due to exposure of the tablet core. Formulators therefore need to consider all potential patient populations when selecting a taste-masking technology for a given drug substance.

Taste masking is, in fact, extremely important for pediatric medications because it can significantly improve adherence in this population, according to Mahmoudi. It can also be more challenging, because the specific age, growth level and physiological development, underlying diseases, and regional/geographical preferences must all be considered during formulation development, including selection of the optimum taste-masking approach. As an example, Mahmoudi observes that market research suggests there are ‘favorite’ flavors that vary from country to country and indication to indication.

In the European Union, for instance, cherry and strawberry flavors are most preferred in pediatric medications for pain and infectious diseases, while lemon, peppermint, and orange are recommended for indigestion remedies (1). In the United States, meanwhile, children prefer grape, bubble gum, and cherry flavors (2).Maintaining a balance is essential

While developing palatable, pleasant-looking dosage forms is the key to improved patient compliance, it is necessary to not make drug products appear to be anything but medicines. “As an industry, we must make sure not to make drugs too appealing,” contends Amoussou-Guenou. “Drugs are just that in the end,” he continues, “and no matter how innocuous they look or taste, overconsumption can lead to serious complications. This consideration is especially important in dosage forms aimed at children,” states Amoussou-Guenou. “Producers must walk a formulation tightrope; not too bitter or bland that kids refuse their medicines, but not too craveable that they start to see potent drugs as candies,” he concludes.

A few opportunities for further development

There are two groups for which advances in taste-masking technologies could benefit. The first is infants and young children that require liquid medications or small particles that can be dosed with milk or soft food. Complicating their development is the need to meet different flavor preferences for different pediatric populations and different types of medications. The best approach, therefore, according to Mahmoudi, is to develop liquid, suspension, or ODT formulations with a neutral flavor or in a variety of flavors to be acceptable by children in different regions. Multiparticulate systems, including those based on pellets and mini-tablets, says Mahmoudi, are one approach that allows the flexibility needed for pediatric formulations.

The second group highlighted by Amoussou-Guenou is surprisingly patients who do not require any special considerations. “It may seem counterintuitive, but this group receives the least consideration when it comes to taste-masking. Of course, strategies for improving medicine accessibility for vulnerable populations are both important and necessary. However, as drug developers rightly become more sensitive to the needs of specific groups, they equally should not forget the fundamentals of making every day medicines more palatable, swallowable, and so on,” he states.

On a positive note, Amoussou-Guenou points to advances in the nutraceuticals segment, such as fun formats like functional gummies with attractive fruity flavors, that potentially have applicability for drug products as well. He also highlights steady improvements to the taste of established delivery methods like effervescent tablets. “These developments underscore the potential gains the pharmaceutical industry could realize by considering a more crowd-pleasing approach to taste masking,” he concludes.

EMA Committee for Medicinal Products for Human Use. Reflection Paper: Formulations of Choice for the Paediatric Population. European Medicines Agency, London, UK, 2006.

Mennella, J. A.; Roberts, K. M.; Mathew, P. S.; and Reed, D. R. Children’s Perceptions about Medicines: Individual Differences and Taste. 

Cynthia A. Challener, PhD, is a contributing editor to 

When referring to this article, please cite it as Challener, C.A. Using Taste-Masking and Appearance to Address Patient-Specific Needs.

The use of appropriate taste-masking and appearance technologies can facilitate patient compliance.

Using Taste-Masking and Appearance to Address Patient-Specific Needs

Tao Peng, PhD, is biopharma research manager at Roquette.

"Primary engines of value creation”—this is the role that leading market commentators see biologic drugs playing in the evolving biopharmaceuticals market (1). Demand for protein-based, large-molecule therapies has been growing steadily for decades, but few could have predicted the boom which followed in the wake of COVID-19. Significantly accelerated by the pandemic, sales of biologic drugs are predicted to exceed those of traditional small-molecule medications by 2027 (1). Runaway demand, exciting scientific breakthroughs, and robust interest from governments and the public: the outlook is bright for biologics. To fulfill this growing potential, producers will need to make drug stability a priority, and this could mean reconsidering the use of a ubiquitous processing ingredient.

Polysorbates (PS 20 and PS 80) are the surfactants most used in biopharmaceutical formulations to protect proteins from denaturation, aggregation, and surface adsorption; these surfactants are present in as many as 90% of marketed therapeutic antibodies (2). Despite their popularity, polysorbates are prone to a number of issues, with serious implications for drug safety, stability, and efficacy. As pressures mount, could it be time for the industry to adopt a new favorite excipient solution for biologics? This article will explore the findings of two recent studies comparing the performance of polysorbates with hydroxypropyl -cyclodextrin (HPβCD)—an alternative biologic stabilizer.

Reliable, multifunctional, and safe, is HPβCD the answer to the question: how do you solve a problem like polysorbates?

To fully understand the “problem” with polysorbates, the industry must examine the essential role ultrafiltration/diafiltration (UF/DF) and protein stabilization during the final formulation stage play in biologic drug manufacturing, and why processing aids are crucial to their success. As 

 shows, UF/DF comes relatively late in downstream biopharma processing, helping achieve the desired concentration and formulation composition of biologics, such as monoclonal antibodies (mAbs) and recombinant proteins. Though an indispensable processing step, the shear stress and continuous adsorption/desorption interactions with the filtration membrane during UF/DF subject active ingredients to harsh conditions. This typically results in protein aggregation and the generation of visible and subvisible particles, jeopardizing the safety and efficacy of the drug. It is here that surface active molecules, such as polysorbates, enter the frame. During high-stress processes, polysorbates act as a chaperone, allowing aggregation-prone hydrophobic sites on the surface of the biologic to pass more easily through membranes to preserve their folded structure and reduce interface exposure (3). 

A brief overview of a typical biologic drug production process.

With decades of evidence pointing to their effectiveness in preventing protein adsorption and aggregation, as well as their demonstrated safety, polysorbate 80 (PS 80) and polysorbate 20 (PS 20) are considered the surfactants of choice in more than 90% of approved mAb products (2). Due to their amphiphilic (both hydrophilic and hydrophobic) properties, mAb proteins have a high propensity for surface-mediated unfolding and adsorbing into interfaces (3). Polysorbates compete with proteins at interface points, reducing the interfacial exposure of the proteins. Despite their widespread use, there are several serious questions surrounding the effectiveness of polysorbates in biologic processing. Polysorbate degradation via oxidation and hydrolysis can produce peroxides and fatty acids that could negatively impact the quality and stability of a medication’s therapeutic protein. Polysorbates can also be nonspecifically absorbed onto UF/DF filter membranes, leading to the formation of micelles bigger than the membrane’s molecular weight cut-off, which in turn causes inconsistencies and membrane blockage. As the biopharma industry moves to make efficiency its central priority, researchers begin to wonder, could an alternative excipient help flip the script?

UF/DF is an integral part of downstream biotherapeutic processing, though it’s not without its challenges. A typical UF/DF process involves several passes through a pump and membrane cassette, often taking several hours to complete (4). During this process, active proteins are exposed to a range of physical stresses, including interfacial interaction, which, as discussed previously, can lead to the formation of higher order aggregates and particulates (4). Therefore, to survive the UF/DF process intact, proteins need an accompanying surfactant to smooth their multiple passes through the membrane cassette and protect them from interfacial stresses (4). For the majority of biologic processing steps, polysorbates are the solution of choice; however, their usefulness runs out by the UF/DF stage. Not only do polysorbate molecules tend to bind nonspecifically with filter membranes, but their propensity to form micelles bigger than the membrane’s molecular weight cut-off can cause filters to become blocked during the UF/DF process (4). Researchers at Roquette postulated that HPβCD could offer biopharma producers an alternative excipient solution, better suited to the requirements of the UF/DF process.

The focus of this study into HPβCD’s potential as an alternative to polysorbates was two-fold: assess its permeability through commonly used filtration membrane types and capacity to reduce particle formation during the UF/DF of human plasma immunoglobulin G (IgG) and adalimumab solutions (4). In the first instance, varying concentrations of HPβCD were observed in the retentate and permeate of solutions passed through a regenerated cellulose-type membrane following centrifugation (4). This indicated that HPβCD may be unsuitable for regenerated cellulose membranes, as it tends to be retained during ultrafiltration (4). With another commonly used polyethersulfone (PES) membrane, however, the results were a complete contrast. In all four variations tested, concentrations of HPβCD remained constant, providing convincing evidence that unlike polysorbates, it is able to pass freely through PES membranes (4). What’s more, these results remained largely consistent when the excipient was tested via an alternative tangential flow filtration (TFF) setup, adding credence to HPβCD’s suitability for UF/DF processes (4).

Regarding the goal of mitigating particle formation, results were similarly promising. Using the same TFF setup, researchers conducted UF/DF experiments using the proteins human plasma IgG and adalimumab in the presence of different concentrations of HPβCD. In the diafiltration setup, both the retentate and permeate were recirculated for four hours to mimic the duration of a typical commercial drug production process. The results at the end of the recirculation process suggested that HPβCD effectively modulated the rate of turbidity (measure of clarity in liquids) increase in the human plasma IgG solution (4). In fact, the turbidity of the sample was reduced by more than two times in the presence of just 10 mM of HPβCD, while dynamic light scattering (DLS) data also showed that it had lowered the relative intensity of larger particles (> 0.1 m) compared to the control sample (4). The addition of a larger, 25 mM concentration of HPβCD reduced the rate of turbidity increase in the adalimumab solution yet further, meaning that the final turbidity was more than four times lower in the sample containing HPβCD than in the control group.

Researchers were able to observe HPβCD’s effectiveness in reducing UF/DF-induced particle formation in both the human plasma IgG and adalimumab solutions too. Looking at the human plasma IgG specifically, a 10% protein loss was observed in the control, whereas all samples containing HPβCD achieved almost complete protein recovery at the end of the four-hour recirculation (4). Not only then is HPβCD suitable for UF/DF where polysorbates are not, but its presence could actually boost efficiencies in biologic production lines—no small point in a time of rising demand for the industry.

The potential benefits HPβCD can bring to the biologic manufacturing process are not exclusive to the UF/DF process. Indeed, this multifunctional excipient exhibits continuous functionality into the final stages of formulation, particularly protein stabilization.

Polysorbates vs. HPβCD: Protein stabilization

The presence of protein aggregates and visible/sub-visible particles within a biologic formulation can compromise product quality and long-term stability, as well as lead to an unwanted immune response in the patient. As such, numerous health regulators around the world require biopharmaceutical companies to closely monitor visible and subvisible particle formation within formulations by comprehensive characterization, as outlined in 

 <789> (5). With scrutiny mounting on the issue of particle formation, recent research has sought to investigate the potential of alternative surfactants that could offer a more stable proposition than traditional polysorbates, with the prime candidate being HPβCD.

Due to its regulatory status as an approved excipient for oral and parenteral administration, HPβCD has been considered as a functional biologic surfactant for more than a decade (6). There is robust evidence to support HPβCD’s effectiveness in preventing thermal or agitation- and lyophilization-induced protein aggregation, in addition to its capacity to reduce interfacial stress-induced particle formation during UF/DF (5). This stabilizing effect has been attributed to the excipient’s ability to reduce protein–protein hydrophobic interactions and displace proteins from interfaces thanks to its weak surface activity (5). Unique properties such as those listed above formed the foundation of a recent investigation into HPβCD as a potential replacement for conventional polysorbates in biologic formulations.

The resultant study compared the chemical stability of HPβCD against that of PS 20 and PS 80 under various stress conditions. This included heat and chemical stressors, as well as its capacity to stabilize proteins within a formulation. When subjected to heat stress, HPβCD showed little change in product recovery (90.7–100.7% recovery depending on the HPβCD grade), while PS 20 and PS 80 both underwent significant degradation, with only 11.5% and 7.3% undegraded product remaining, respectively (5). Similar results were recorded when the surfactants were subject to autoclave, light, and oxidative stresses, with the HPβCDs remaining almost completely stable, while both polysorbates displayed some level of degradation (95.5%–98.8% usable product remaining for PS 20 and 85.5%–97.4% for PS 80) (5).On closer analysis, researchers found the HPβCDs’ chemical structure remained consistently stable, compared to the significant hydrolytic degradation and oxidation seen with the polysorbate molecules (5).

Finally, attention turned to HPβCD’s performance as a functional surfactant in a test formulation. Researchers evaluated the stability of various model mAbs when subjected to light stresses. Compared with the more traditional PS 80 preparation, the mAb formulated in the presence of HPβCD showed a notable decrease in protein aggregation, a superior monomer, and total protein recovery while reducing both protein aggregation and subvisible particle formation (5). Evidently, HPβCD excipients hold immense potential as biologic stabilizers.

At the end of this compare-and-contrast exercise, it is important to acknowledge the real value polysorbates bring to biologics processing. In a wide array of applications, they act as effective buffers and mediating agents, and their years of evidence as safe and nontoxic excipients cannot be discounted—but neither can the clear potential of HPβCD. In the studies discussed above, it can be seen what a significant impact stabilizing cyclodextrins could have on protein stability, mitigating particle formation, and streamlining vital processes. In some instances, such as UF/DF, substituting traditional polysorbates for HPβCD appears to be the logical choice, but this will not be so clear cut in every scenario. The future of biologics processing then could be one where these two surfactant groups are used interchangeably or even in tandem, to produce the very best outcomes for patients. That is, after all, the ultimate problem every drug producer is seeking to solve.

Biologic Sales to Pass Innovative Small Molecules in Next Five Years, Says GlobalData

, May 10, 2022.
2. Bollenbach, L.; Buske, J.; Mader, K.; Garidel, P. Poloxamer 188 as Surfactant in Biological Formulations—An Alternative for Polysorbate 20/80? 

, 121706.
3. Grabarek, A. D.; Bozic, U.; Rousel, J.; et al. What Makes Polysorbate Functional? Impact of Polysorbate 80 Grade and Quality on IgG Stability During Mechanical Stress. 

 (1), 871–880. DOI: 10.1016/j.xphs.2019.10.015
4. Hong, S.; Peng, T.; Gokhale, R. Mitigating Particle Formation During Ultrafiltration/Diafiltration of Biologics with KLEPTOSE HPβCD (Hydroxypropyl Beta-Cyclodextrin). Whitepaper, 2023.
5. Zhang, H.; Hong, S.; Tan, S. S. K.; et al. Polysorbates versus Hydroxypropyl Beta-Cyclodextrin (HPβCD): Comparative Study on Excipient Stability and Stabilization Benefits on Monoclonal Antibodies. 

, 6497. DOI: 10.3390/molecules27196497
6. Serno, T.; Carpenter, J. F.; Randolph, T. W.; Winter, G. Inhibition of Agitation-Induced Aggregation of an IgG-Antibody by Hydroxypropyl-Beta-Cyclodextrin. 

When referring to this article, please cite it as Peng, T. Polysorbates: Part(icle) of the Problem? 

A comparison between polysorbates and HPβCD determines the better stabilizer for biologics formulation.

Polysorbates: Part(icle) of the Problem?

Bianca Piachaud-Moustakis is lead writer at Pharmavision, Pharmavision.co.uk.

On 19 Sept. 2023, the Innovative Devices Access Pathway (IDAP) pilot scheme was launched in the United Kingdom. IDAP aims to enable and improve patient access to innovative and transformative medical devices, including diagnostics and digital health solutions, and to provide manufacturers with an integrated and enhanced regulatory and access pathway. According to the UK government, the pilot phase aims to “test the main elements of the pathway and provide informative learning and feedback that helps to build the future IDAP” (1). The scheme stems from the policy paper Life Sciences Vision, published in July 2021, which set out the UK government’s intention to strengthen access and the uptake of innovation (2).

The IDAP comprises a network of partner organizations that include the Department of Health and Social Care (DHSC), Health Technology Wales (HTW), Medicines and Healthcare products Regulatory Agency (MHRA), National Health Service England (NHSE), National Institute for Health and Care Excellence (NICE), Office of Life Sciences (OLS), and the Scottish Health Technologies Group (SHTG) (3). The scheme is backed by £10 million (€11.7 million) of government funding and provides faster access to cutting-edge medical device innovations for patients through targeted support for innovators in exchange for allowing the NHS to have access to their technology.

The successful applicants will receive non-financial, multi-partner support and specialist scientific advice from a team of experts to develop a product-specific Target Development Profile (TDP) roadmap. The TDP roadmap will define regulatory and access touchpoints across the product development cycle and could include:

a fast-tracked clinical investigation review

dialogue to discuss potential reimbursement options

exceptional use authorization granted by MHRA, provided that necessary safety standards are met system navigation advice

safe-harbour meetings with Health Technology Assessment (HTA) Authorities, the NHS, and other key system stakeholders to discuss product realization, NHS adoption, and commercial challenges (1).

This collaborative approach is also designed to ensure that intellectual property considerations are fully integrated into the regulatory process.

Eligibility criteria used in the IDAP pilot

To be eligible, applicants had to submit devices that did not have a CE mark, UK CA mark, or regulatory approval. In addition, proof of concept evidenced by data to a near-final prototype had to be demonstrated. At the same time, clinical input from at least one UK health organization or medical charity must already have been obtained by the developer (4). According to UK government stipulated guidelines, the following eligibility criteria had to be met:

Applicants are expected to have identified clinical investigation sites and ideally have signed agreements in place.

For early-stage health technologies, organizations must demonstrate a proof of concept evidenced by data from a near-final prototype.

Organizations must have a recognized quality management system in place. Whilst certification is not mandatory, the system must satisfy the requirements of ISO 13485 or equivalent.

The applicant must intend to market the health product in the UK and intend to obtain regulatory authorization.

The applicant must commit to working with the IDAP partners to create a TDP.

The lead applicant must be a legal entity with the rights to market their health product in the UK (1).

The IDAP pilot scheme was open (from 19 Sept. to 29 Oct. 2023) to applications from commercial and non-commercial developers from the UK and international markets who have developed new medical devices. In its updated guidance, the UK government announced in February 2024 that eight innovative medical devices had been selected, which are summarized in 

Applicants for the Innovative Devices Access Pathway (IDAP) pilot scheme.

However, according to government-mandated guidelines, those companies that were ineligible to apply to the programme included developers that produced drug medical device combination products (e.g. a medical device and a medicinal product that constituents parts, such as autoinjectors, inhalers, pre-filled nebulizers, pre-filled pens, pre-filled syringes, and transdermal patches); and legal entities headquartered or operating out of jurisdictions that are the subject of UK Government sanctions.

The updated guidance document published by the UK government in February 2024, stipulates that several criteria must be met for inclusion in the pilot programme (

Criteria for inclusion in the pilot programme. 

According to the UK government’s IDAP pilot application guidance document, “the IDAP pilot phase has been restricted to eight technologies/devices to ensure the selected products will derive maximum benefit from their inclusion on the pathway and to enable comprehensive insights and knowledge to be integrated into the future IDAP” (4). The overall ambition of developing an end-to-end innovative pathway for developing and adopting innovative technology into the NHS is a priority set out in the Medical Technology Strategy published in February 2023.

The establishment of the new IDAP, designed to provide faster access to innovative medical technologies, is a pioneering legislative proposal in the UK medical device space that has potentially significant implications for patients and businesses. This scheme is set to create opportunities for real-world data collection, which can enhance the value proposition of products and give businesses a competitive advantage by allowing innovators to rapidly penetrate the UK market and build a strong patient base (5).

The IDAP initiative also seeks to streamline the regulatory process by reducing delays and bureaucracy and thereby bringing medical technology solutions to patients more quickly. It forms part of a broader package of reforms to the UK’s medical devices regulatory framework that the government is planning to introduce in a phased approach. The second stage of IDAP implementation is expected to include legislative changes that will mirror the Innovative Licensing and Access Pathway initiative for medicines, established in March 2021, designed to give patients quicker access to cutting-edge treatments and therapies by offering a streamlined approach to licensing and regulatory processes (6). Through these changes, the UK could become a more attractive destination for medical technology adoption, thereby ushering in a new era of innovation and accessibility in the healthcare sector.

The IDAP pilot scheme is designed to accelerate access to innovative medical devices and is a pioneering legislative proposal in the UK medical device space.

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