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

Navigating FDA Shakeups and Obesity Drug Wars

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

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

Gene Therapy for Cancer Treatment Concept Cancer therapy with T-cell and pipette |©catalin - stock.adobe.com

While many stem-cell therapies remain at the preclinical stage, several are progressing through the clinic toward late-stage trials. Developing successful treatments based on induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) in part depends on creating effective formulations in which cell viability is maintained during cryopreservation, storage and handling, shipment, and reconstitution prior to delivery to the patient. Excipients, therefore, play an important role in bringing novel cell therapies to the market.

Buffers, stabilizers, and cryoprotectants

As with most biologic drug products, the predominant excipient in cell therapy formulations is the buffered saline solution. In this case, the saline solution is an osmotically balanced water solution designed to keep the cells from drying out and dying, according to Ryan Guest, senior CMC translation consultant for eXmoor pharma.

In addition to physiological saline, Carole Nicco, CSO at BioSenic notes that other isotonic solutions containing chemical substances present in blood, such as Ringer’s lactate, are also used to help maintain the electrolyte balance and keep the cells stable, sterile, and viable with proliferative capacity until their application. Furthermore, these isotonic solutions offer chemical easy systemic and local application, according to Nicco.

Classically, most formulations will also have protein to balance the solution as a buffer or reservoir for smaller molecules and enable transport via active protein transporters on cell membranes, Guest notes. The standard is an albumin (0.5–2.5%), such as human serum albumin. Albumin constitutes 50–75% of the colloidal osmotic pressure of blood (1–3) and performs a very similar role in MSC and iPSC formulations, Guest says. More specifically, albumin is a useful component in cell therapy formulations for balancing water availability during product hold times, cryopreservation, and thawing prior to product administration.

In fact, Guest observes that the presence of an equivalent protein in cell therapy formulations is predicted to have a significant impact on cell survival. In MSCs, for instance, the absence of an appropriate protein can reduce viable recovery by 20–40%, he comments.

The other important excipients for cell therapy products are cryoprotectants, given that the majority of these treatments are cropreserved. The cryopreservation of MSC- and iPSC-based therapies using 2–10% dimethyl sulfoxide (DMSO) in solutions containing a high content of serum is a common procedure, Nicco observes. She adds that while DMSO has been used to reduce the formation of ice in cells stored in liquid nitrogen since 1959, it is toxic, resulting in undesired clinical and biological side effects. Serum also introduces variation and safety risks.

“There is, consequently,” Nicco says, “a move toward solutions containing bio-preservation media free of DMSO, serum, and other proteins, optimized for the preservation and distribution of these products at low temperatures, either in cold (2–8 °C) or cryopreserved conditions (-70 °C to -196 °C).” The new excipients, she explains, eliminate toxicity issues as well as the need for human product excipients (serums, proteins) that can induce a risk of contamination to the drug product. Complex formulations involving dextran-40, lactobionate, sucrose, mannitol, glucose, adenosine, and/or glutathione are examples, according to Guest.

Intended application key driver of excipient choice

The type of stem cell therapy generally does not impact the choice of excipients, although Guest does note that some iPSCs can be more acutely sensitive to the final formulation, hold times, and routes of administration. For example, anucleated products, specifically designed to deliver payloads, have a reduced capability to produce proteins or perform cellular repair. Nicco adds that iPSCs and cells differentiated from them are commonly multicellular systems, which she says also makes them more sensitive to the stresses of freezing and thawing than single cells.

Overall, however, similar types of excipients are used for the preservation of cell-based therapies, regardless of the cell type or method of manipulation, according to Nicco. “It is the route of administration, the need for transport, and the storage temperature that influence the choice of excipients,” she states.

Special applications, for instance, such as therapies for artificial skins and wound healing may have specific properties or additional ingredients for sealing the wounds, Guest notes. Hence, the excipients or scaffolds are part of these therapies. Dosage size is another important factor, he adds. “Larger doses need to take into account any toxic side effects of the excipients, such as DMSO, and may place maximal limits upon the total volume of excipients to be administered,” he observes.

Always consider the route of administration and freezing requirements

One of the most critical issues for cell therapy manufacturers is the maintenance of the cells in an appropriate medium/excipient from the end of the culture until the time of administration to the patient. “Not only should the medium keep the cells viable with their properties intact, but the route of administration must also be taken into account,” Nicco states. She adds that a good excipient “is solvent-free and suitable for fresh or frozen suspensions of living cells formulated in a proprietary formulation adapted to the route of administration, such as intravenous, intra-articular, or intracranial.”

In addition to understanding the delivery mechanism, Guest stresses the importance of considering the container and dose when choosing excipients. The next important factor, he says, is whether the cell therapy product will be supplied frozen, as that will require selection of a cryoprotectant. Formulation development experiments should then be designed carefully to optimize potency while taking into consideration hold periods and freeze/thaw steps and eliminating or otherwise minimizing the use of diluents and wash steps. In addition, Guest recommends evaluating existing administration formulations, containers, equipment, and protocols to minimize the need for new or changes to clinical practices.

An important component of any formulation strategy is consideration of the raw materials.For excipients intended for use in cell therapy products, Guest emphasizes the need to identify available good manufacturing practice (GMP)-suitable sources with acceptable lot-to-lot controls that will enable a reproducible product formulation. It is also critical, he says, to confirm the material is suitable for the manufacturing process and will be available to meet manufacturing demand for the cell therapy throughout its product life cycle.

Equally important, Guest observes, is to ensure the availability of suitable cellular material and drug product for designing formulation experiments. Understanding the patient group and the intended administration route are essential, meanwhile, for identifying potential side effects of any excipients.

Compendial excipients are generally preferred, Guest continues, due to the risk that novel or untested solutions will require significant development to ensure the material does not impact upon the therapeutic benefit of the cellular material. In addition, all materials including excipients must be suitable for the intended route of administration and present minimal risk of inducing toxicity, immune reactions, or the transfer of adventitious agents.

Assessing formulation stability and quality

Controlling cellular material from the point of “optimal” donor selection to manufacturing under GMP conditions, commercialization, and application is critical for ensuring the quality, safety, and efficacy of the final drug product. While MSCs used as starting materials for production of advanced therapy medicinal products can only be isolated in authorized centers using globally standardized processes, the optimal conditions for culturing isolated MSCs are not standardized. That poses a major challenge in controlling their quality and therapeutic properties, Nicco contends.

It is, therefore, essential to control the cell sources (e.g., bone marrow, umbilical cord, and adipose tissue), cell density in culture, duration of culture, and cell engineering and composition of culture media and implement in-process quality controls that ensure cell efficacy and safety at all stages of manual and automated manufacturing processes, including cryopreservation, use of cell banks, and transport systems. “Ultimately, the stability and quality of the cell therapy product and the excipients it contains must always be evaluated against reference samples submitted to the same storage facility,” emphasizes Nicco.

Complicating this situation is the fact that it can be difficult to find reliable mode-of-action potency methods for cell-based therapies, according to Guest. “Often both 

 models are required to confirm the suitability of the formulation,” he says.

In addition, formulation strategy, hold times, cryopreservation, and thawing are intrinsically linked, and it can be difficult to determine the impact of each component of the formulation, Guest observes. “Doing so requires carefully designed experiments and suitable analytical methods that assess not only the impact of formulation changes and freezing and thawing processes, but downstream biological mechanisms such as apoptosis and necrosis, which require time in a suitable cell-culture facility or 

 models to optimize formulations,” he explains.

“A further difficulty rests with the fact that viability determinations are often tied to the analytical methods, the technicians performing them, and whether biological mechanisms of apoptosis and true cell recoveries are accounted for in the testing strategy,” Guest comments. Therefore, it is important for cell therapy developers relying on external testing laboratories to ensure those outsourcing partners have the proper understanding, expertise, and capabilities needed for appropriate and comprehensive testing.

Advances in cell therapy formulation science underway

The cell therapy field is expanding at a rapid rate, and technology is advancing to support the increasing breadth of treatments under development. That includes formulation science and the development of enhanced excipient solutions. Cryoprotectants developed through biomimicry of natural antifreeze proteins to replace DMSO and serum protein-based media are one example highlighted by Nicco.

More work is to be done in this area, however. “There is a clear unmet need for the discovery and development of novel cryoprotectants that can either replace or reduce the required amounts of current gold standards formulated to protect and treat challenging sample types such as MSCs and, even more, iPSC multicellular systems. This multivariate problem is complex, with multiple mechanisms of damage to be addressed and subtle differences between cell types and freezing methods. Combining high-throughput testing with iterative computational algorithms is key to optimizing protocols and excipient formulations to preserve emerging cell-based therapies,” Nicco comments.

Guest, meanwhile, predicts that as the cell therapy field advances, clinical practice will naturally standardize formulation, delivery, and routes of administration through product safety and efficacy data. “That will include the use of animal-free or recombinant excipients and other fit-for-purpose additives developed through the use of artificial intelligence to minimize cytotoxicity while improving stability and hold times,” he states.

Nicco is also confident that the combination of new technologies such as intelligent library design, computational modeling, rapid screening assays, and advances in genomics will lead to a better understanding of the structure-function relationships between drug and excipient. “That greater understanding will lead to more effective and efficient excipients that afford higher-performing cell therapies and ultimately benefit both cell therapy developers and patients,” she concludes.

Valerio, C.; Theocharidou, E.; Davenport, A.; Agarwal, B. Human Albumin Solution for Patients with Cirrhosis and Acute on Chronic Liver Failure: Beyond Simple Volume Expansion. 

 Mar 8;8(7):345-54. doi: 10.4254/wjh.v8.i7.345. PMID: 26981172; PMCID: PMC4779163.

Hankins, J. The Role of Albumin in Fluid and Electrolyte Balance. 

 Sep-Oct;29(5):260-5. doi: 10.1097/00129804-200609000-00004. PMID: 17035887

Shah, M.M.; Mandiga, P. Physiology, Plasma Osmolality and Oncotic Pressure. [Updated 2022 Oct 3]. In: 

 [Internet]. Treasure Island (FL): StatPearls Publishing; 

 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544365/.

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


Vol. 48, No. 1
January 2024
Pages: 20–21, 25

When referring to this article, please cite it as Challener, C.A. Choosing the Right Excipients for MSC and iPSC Therapies. 

Articles

Buffers, stabilizers, and cryoprotectants play major roles in cell therapy formulations.

Choosing the Right Excipients for MSC and iPSC Therapies

Hallie Forcinio is packing editor for Pharmaceutical Technology and Pharmaceutical Technology Europe, editorhal@sbcglobal.net.

Secondary packaging for pharmaceutical products must navigate global and local challenges and address a myriad of demands with sustainability at the top of the list. Other secondary packaging trends stem from the need for more complex carton designs, kitting, and the incorporation of child-resistant, serialization, anticounterfeiting, or smart features. These needs are generating advances in coding, marking, and printing. There’s also a growing reliance on suppliers for design assistance so cartons, labels, and leaflets run efficiently on the packaging line, protect the product throughout the supply chain, and meet the requirements of regulators, drug makers or contract manufacturing/packaging organizations, caregivers, and patients.

Consumer preference is a driving force in the attention given to sustainability. Erwin Klünder, head of Sales, Healthcare & Flexibles at Graphic Packaging International (GPI), says, “Consumers want to make more sustainable purchasing choices, a sentiment shared by patients in the pharmaceutical industry (1). Those patients expect companies to help them achieve that goal by providing the right products—including the packaging.”

In line with this sustainability focus from the consumer as well as increased pressure from regulators to reduce waste, “brand owners are trying to showcase their commitment to sustainability,” reports Ward Smith, director of Marketing & Business Development for Keystone Folding Box.

Marga Romo, head of Marketing at MM Packaging, a division of MM Group, notes as new products are developed, “… pharma businesses must have absolute awareness of the product’s total environmental footprint, before the product hits the market. This includes an assessment of the full supply chain for Scope 3 emissions. … we factor this into our manufacturing operations by prioritizing resource-optimized production and recyclability … and moving toward a true circular economy.”

Sustainable packaging involves reducing or eliminating plastic, lightweighting and downgauging, transitioning to more-recyclable packaging materials to achieve a circular economy, adopting renewable paper-based options, rightsizing (cube efficiency), and minimizing the number of packaging sizes and configurations, adds John Lackner president/COO of Colbert Packaging.

An exception to adopting a more-recyclable material like paperboard is products destined for surgical areas. For this environment, pharmaceutical manufacturers want a material that looks clean. “It’s all about appearance and cleanliness,” says Paul Glintenkamp, vice-president Sales at Aphena Pharma Solutions, a contract pharmaceutical manufacturing and packaging company. Some drug makers have overcome this concern by specifying paperboard that is coated on both sides.

Advances in coding, marking, and printing

Increasing regulation is spurring demand for enhanced coding, serialization, and pre-serialization technologies to provide product security and fight counterfeiting. This has prompted innovations in carton design as well as coding, marking, and printing functions on packaging lines.

Keystone Folding Box frequently provides guidance about graphic changes to optimize laser or inkjet printing of serialization, lot, and expiry information. In some cases, Smith says, customers are requesting the addition of QR codes that direct patients to additional information or instructions about the medication.

Aphena Pharma Solutions, which offers three levels of serialization, assists customers with package and carton design to ensure serialization will not disrupt packaging line efficiency. This means designing the cartons so codes will be readable without extra manipulation. “Marketing professionals and graphic designers don’t always think about how internal packaging systems or bundling requirements may complicate online code reading,” explains Glintenkamp.

Additionally, concern about code clarity and smudge-free readability is expanding interest in laser coding. “[Aphena] recently added laser coders on two lines and is doing shipping studies to verify the laser-printed code is less prone to scuffing than an inkjet-printed code,” says Glintenkamp.

Laser coding, which is considered to be cleaner, faster, and more efficient than alternative technologies, is the focus of MM Packaging’s Clear Code pre-treatment coating that enables precise and durable high-contrast patterns to be applied using carbon dioxide, fiber, or yttrium aluminum garnet laser energy.

GPI’s highly flexible serialization service meets the demands of the most recent drug traceability specifications and can accommodate longer or more complex coding requirements, including compliant European Union (EU) codes, Chinese C128 codes, veterinary codes, and more country-specific formats, such as Italian Bollini labels.

Colbert Packaging also can address an array of coding needs including item-level identification and traceability based on country of origin and helps ensure folding cartons are ready to receive serialization codes on the packaging line.

Furthermore, coding, marking, and printing technologies enable the late-stage customization needed as lot sizes shrink to address the growing availability of patient-specific drugs and treatments for rare diseases. “Packaging processes need to ensure individual information can be printed in highly efficient and automated ways (for example, specific language versions for countries with lower volume demands),” says Klünder.

New folding carton designs and the evolution of wallet packs address the demand for sustainable, child-resistant, and smart packaging options. Sustainability can be enhanced by changing materials to incorporate fiber-based content that can meet performance requirements while increasing the circularity of the package. “These materials can be used alone or combined with barrier coatings or films to create hybrid solutions,” reports Klünder. Additionally, print finish advances using metallic effects or water-based inks can replace metallized polyethylene terephthalate/paperboard laminates with a more-recyclable paperboard.

Adoption of wallet packs, which help patients take each dose correctly, will continue to grow particularly for products that involve complex dosing regimens or serious warnings about proper use and contraindications. For example, the Key-Pak F1 wallet card from Keystone Folding Box holds blister packages of solid dosage forms, provides child resistance, and allows for the integration of smart technology that monitors and records data related to dosage removal.

One smart, child-resistant design integrates the Key-Pak wallet with electronics from Schreiner Medipharm to provide a real-time e-diary for dosing history. The integration of conductive trace-patterns linked to each of the cavities generates data the instant the patient removes a dose. Details, such as time and date of removal and cavity location, are stored within the onboard electronics and can be transmitted by near-field communication (NFC) or Bluetooth technology for precise patient compliance tracking. It’s also possible to send medication dosing reminders to patients and to adjust therapy plans. When used in combination with special software, central tracking as well as data documentation and analysis are possible. The design accommodates virtually any dosing regimen by customizing the number, arrangement, and shape of the blister cavities. The improved data quality can expedite the clinical trial process and accelerate the approval of a new drug (2).

Another design from Keystone Folding Box, the Ecoslide-RX blister pack wallet, provides a child-resistant alternative to high-density polyethylene vials and amber polypropylene prescription vials, which are rarely accepted in US recycling streams. According to Smith, the package is engineered to use the least amount of film and foil, maximize manufacturing efficiencies, and run at high speeds on existing equipment. He reports, “The switch from a bottle/vial to an Eco-slide-RX blister package results in significantly reduced plastic—in some case up to 75%. Even more sustainable benefits are achievable by utilizing newer recyclable blister materials.”

Colbert Packaging also offers paper-based alternatives to plastic packaging. Its water- and agri-based One Clean Carton offers low migration, low odor, and low levels of volatile organic compounds. Like many secondary packaging suppliers, the company embraces sustainable practices across its supply chain, using wood fiber from certified sources. In addition, “investment in wind RECs (renewable energy credits) supports [Colbert’s] sustainability program, and [its] participation with the EcoVadis sustainability ratings platform enables [the company] to continually address and improve overall sustainability efforts,” says Lackner.

Stakeholders predict the demand for sustainable packaging will intensify in 2024–2025 as the sector grapples with evolving legislation, including the EU’s proposed Packaging and Packaging Waste Regulation (PPWR), United Kingdom Green Claims Code, EU Green Claims Directive, and extended producer responsibility schemes being introduced around the world.

Regulations and national and international collaborations will propel efforts to be more sustainable. For example, the US Plastics Pact is bringing together the plastics value chain to reconsider the design, use, and reuse of plastics. “The overarching objective is to diminish plastic waste in our environment and establish a circular economy for plastics,” says Smith.

Sustainability will take on even greater urgency when the PPWR is approved because it brings the recyclability of pharmaceutical packaging under the scope of packaging waste legislation for the first time. Klünder explains, “This means healthcare packaging must be designed to facilitate efficient recycling and be easy to collect and sort into separate waste streams. It must also result in secondary material that is of sufficient quality to substitute for primary material. Paper-based materials, used in cartons and corrugate, are the obvious choice to help the industry rethink its secondary and tertiary packaging. They are already capable of being recycled at scale—figures show 82.3% of fiber-based packaging is recycled in Europe (3), along with 81% in the USA (4)—and can easily meet Design for Recycling criteria.”

“We believe that the initial emphasis will be on reducing the overall plastic content in pharmaceutical packaging, [and] … transitioning to easily recyclable cartons,” says Romo of MM Packaging, which is developing paperboard options with recycled content with the help of sister company, MM Board & Paper.

Beyond sustainability, other growth areas include a continued emphasis on quality with broader use of vision systems at all stages of secondary packaging production and the continued adoption of smart packaging technologies. Increasingly based on radio frequency identification and NFC technology, smart packaging can turn individual packaging units into traceable data points, unlocking new heights of transparency and enabling pharma businesses to make data-driven decisions regarding the supply chain. “The … pharma sector will see smart, connected packaging playing a more central role in preserving patient safety,” predicts Romo.

Anticounterfeit and security features will continue to evolve to protect products, brands, and consumers. Layered overt and covert anticounterfeit technologies will be needed to discourage counterfeiting of rapidly growing, high-value products like anti-obesity treatments.

Growth in self-administered products will impact packaging design and supply chain processes. “A patient-centric approach to packaging design will be key to enhancing the patient experience and enabling accessibility for people with different physical needs or reduced motor capabilities,” says Klünder.

With all this activity and the expanding development of biosimilars and new drugs, Glintenkamp predicts contract manufacturing and packaging capacity will tighten. As a result, contract manufacturing and packaging organizations will need to boost their workforce and, in some cases, add capacity.

1. Shorr Packaging, The 2022 Sustainable Packaging Consumer Report. White Paper. July 20, 2022.
2. Schreiner MediPharm. Schreiner MediPharm Enables Digital Adherence Monitoring with New Child-Resistant Smart Blister Wallet. Press Release. Nov. 28, 2023.
3. 4evergreen. A Journey through Recycling of Fibre-Based Packaging. 

. Accessed Dec. 7, 2023.
4. Two Sides North America. Paper-Based Packaging Is Recycled More than Any Other Packaging Material. 


Vol. 48, No. 1
January 2024
Pages: 22–25

When referring to this article, please cite it as Forcinio, H. Navigating Trends in Secondary Packaging. 

Designers adopt value-added features, different materials, and enhanced coding technologies.

Navigating Trends in Secondary Packaging

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

3D Rendering of earth from space with run rising and ray light flare at horizon among glowing stars in galaxy. For wallpaper, sci fi, science or technology background | Image Credit: © knssr – Stock.adobe.com

A key political decision from 2023 that will undoubtedly impact the scientific communities of both the United Kingdom and European Union has been the allowance of the UK to re-enter the Horizon Europe research programme (see 

) (1). After voting to depart from the EU in 2016 and finally severing from the union in 2020, the UK has been excluded from full membership of certain EU projects, such as Horizon Europe. However, in March 2023, after the implementation of the Windsor framework (2,3), discussions commenced between the regions with the aim of getting the UK reinstated into the Horizon Europe research programme (4).

On 7 Sep. 2023, the UK and EU agreed upon a new bespoke deal, allowing the UK to participate in the Horizon Europe programme as well as the EU’s Earth observation programme, Copernicus (5,6). UK scientists were able to apply for grants and could bid to participate in projects from the date of the deal announcement (7 Sep. 2023), and from 1 Jan. 2024 are able to formally participate in Horizon Europe on par with EU counterparts with access to funding (6).

“The EU and UK are key strategic partners and allies, and [this] agreement proves that point. We will continue to be at the forefront of global science and research,” specified Ursula von der Leyen, president of the European Commission (EC) in a press release about the deal (6).

Horizon Europe is the European Union’s (EU’s) seven-year research and innovation funding programme that has succeeded the Horizon 2020 programme. Across seven years, researchers and innovators can apply to receive a grant from the programme’s budget which is worth a total of €95.5 billion, making it the largest civil research and innovation programme.

Consideration of funding for the programme is split into three main pillars: excellent science; global challenges and European industrial competitiveness; and innovative Europe. Any EU member state and associated countries can participate in the programme.

More information can be found on the European Commission’s website: 

https://research-and-innovation.ec.europa.eu/funding

Many in the scientific research communities of both the UK and Europe have been grateful to see this deal finalized. “[The] announcement on the UK’s association to Horizon Europe and Copernicus is a cause for celebration on both sides of the channel,” said Dr. Michael Spence, president and provost of University College London, in a news release (7). “Association to Horizon Europe will enable research, which makes a positive difference to people’s lives, supporting vital research and innovation networks and strengthening the UK’s position as an attractive destination for talent.”

The deal is a particular boon to those in the UK’s scientific community who were facing uncertainty due to limited funding opportunities for research. “The lack of agreement to allow the UK to continue to play a full role in the EU Horizon funding programme severely threatened [UK science] continued success,” explained Professor Liam Smeeth, director of the London School of Hygiene and Tropical Medicine, in a news release (8). “My concern was particularly for the long term. With no new partnerships and collaborations being formed, there was a very real risk of the UK becoming isolated and insular.”

Mayer Schreiber, CEO of Discovery Park, emphasized the importance of collaboration in the science community. “Collaboration is vital to successful science and innovation and the funding and partnership opportunities the programme offers will bring considerable benefits to the UK and Europe,” he said in a press release (9).

Now that the UK is fully reinstated into the Horizon Europe programme, reforging research relationships that have been lost in the interim will be vital. According to Thomas Jørgensen, director for Policy Coordination and Foresight at the European University Association, trying to get the level of cooperation back to where it was prior to the UK’s removal from the programme will be the biggest challenge (10).

Adding to this challenge will be issues such as the UK and EU’s divergence in regulations and standards, such as the rules around digital platforms, and the European view on certain sensitive subjects, such as the development and sharing of strategically important technologies, asserted Jørgensen (10).

However, on a positive note, the hiatus from the programme has finally come to an end, and UK-based researchers are once again able to receive funding and lead research projects involving multinational consortia. “Joining the Horizon Europe programme is a huge win for the scientific research community, who have been pushing for resolution over the past few years,” specified Janet Valentine, executive director of the Association of the British Pharmaceutical Industry, in a response to the deal. “UK innovation and research depends on international collaborations, which are crucial for driving advancements in all areas of science, including the discovery and early development of new medicines and vaccines. The UK accession to Horizon enables the two sides to reinvigorate their longstanding partnership in R&D, and directly contributes to UK growth and competitiveness in the life sciences sector by making the UK an attractive destination for talented researchers” (11).

. Policy Paper, 27 Feb. 2023.
3. European Commission. Protocol on Ireland and Northern Ireland: The Windsor Framework. 

 (accessed 10 Jan. 2024).
4. Gallardo, C. Britain and EU Agree Draft Horizon Deal. 

, 5 July 2023.
5. UK Gov. UK Joins Horizon Europe Under a New Bespoke Deal. 

, Press release, 7 Sep. 2023.
6. European Commission. EU-UK Relations: Commission and UK Reach Political Agreement on UK Participation in Horizon Europe and Copernicus. 

, Press Release, 7 Sep. 2023.
7. UCL. Rejoining Horizon Europe is a ‘Cause for Celebration’. News Release, 7 Sep. 2023.
8. LSHTM. Expert Comment—UK Rejoins Horizon Programme. News Release, 8 Sep. 2023.
9. Discovery Park. Discovery Park Welcomes Decision to Re-Join EU Horizon Science Programme. 

, 7 Sep. 2023.
10. Jørgensen, T. So the UK is in Horizon Europe—Now What? Research Professional News, 19 Sep. 2023.
11. ABPI. ABPI Response: UK Joins Horizon Europe. News Release, 7 Sep. 2023.

Felicity Thomas is the European/senior editor, and Jill Murphy was the former editor for Pharmaceutical Technology Group


Vol. 36, No. 1
January 2024
Pages: 32–33

When referring to this article, please cite it as Thomas, F.; Murphy, J. Bringing Collaboration to the Horizon Once More. 

UK scientists are once again able to participate in the Horizon European research programme thanks to a deal struck in 2023.

Bringing Collaboration to the Horizon Once More

Side view portrait of pretty young woman wearing lab coat and using digital tablet in modern factory workshop, copy space |©Seventyfour - stock.adobe.com

Validating the effectiveness of the cleaning of pharmaceutical manufacturing and process equipment is part of good manufacturing practices (GMPs) (1,2). Regulators expect manufacturers to be able to show that their cleaning process is sound. Analytical methods and tools assist in assuring that equipment is clean and ready for use. “An analytical method provides an independent assessment that the equipment [being used] for a client’s product is clean,” according to Wayne Goodwin, director, Quality Operations at BIOVECTRA.

Preventing cross contamination between manufacture of different products is of primary concern. Residue from a previous product must be reduced to acceptable levels before equipment can be used to manufacture a new product, remarks Goodwin. Regulators, and clients, need to be assured that this has been done. “[Regulators and clients] want the entire cleaning package, including work instructions for cleaning the equipment and results of rinse and swab testing. They routinely review the method validation reports which support the analytical methods,” he says. “[Manufacturers] also must show that [the] cleaning acceptance criteria are appropriate as [they] clean from Product A to go into Product B. The justification typically includes an acceptable daily exposure (ADE) limit for the outgoing product and also incorporates factors such as shared equipment surface areas and the rinse and swab recovery factors for the
outgoing product.”

Analytical procedures can be used to quantitate if residuals of a drug product or cleaning agent remain on equipment after it has been cleaned, asserts Shailesh Vengurlekar, senior vice president of Quality and Regulatory Affairs, LGM Pharma. “Determining or quantitating the left-over residues helps reduce the risk of cross contamination or adulteration of products,” he says.

When creating an analytical method to ensure cleaning validation, the type of residue being measured, the sampling method, and the residue acceptance limit (RAL) in the sample should all be considered, according to Vengurlekar. “The selection of an analytical method depends on the chemical nature of target residues and analytical limits established for those residues. A key element in the selection of an appropriate analytical method is that the method produces a result that has a logical, scientific link with the target residue,” he says. The method or procedure should confirm residue has been removed from the equipment during cleaning. “The analytical procedure is first developed and validated to ensure that the drug substance can be recovered/detected using that methodology,” says Vengurlekar. “The validation of a cleaning validation analytical method for product residue must be based on the RAL calculated for that material as defined in a cleaning validation plan. The method may be considered valid for any RAL within the validated RAL recovery range. If the RAL is outside this recovery range, the method must be revalidated with respect to the affected parameters/characteristics.”

According to Goodwin, an appropriate analytical method for cleaning validation includes limit of detection, quantitation of the method, specificity, and recovery studies from both the rinse and swab samples. “Data from the cleaning validation exercise demonstrate that the method is suitable for use,” he states. “If a product goes into [the] GMP equipment, then a cleaning method validation [is needed] regardless of the lifecycle status of the previous product.”

Analytical procedures should be meticulously designed, stresses Goodwin, to detect impurities and confirm cleanliness. “A ‘non-detect’ result may arise if our testing methods lack sensitivity for the target analyte,” he says. A method should attain the necessary specifications. “For cases when the preferred method for a particular product isn’t sensitive enough to detect low levels, we’re obligated to find an alternative method with sufficient sensitivity,” Goodwin confirms.

The method should also fit the needs of the production facility, Goodwin continues. “For example, our preferred method might use HPLC [high-performance liquid chromatography] with methanol as the diluting solvent. However, if that area of the production facility is not rated for flammable solvents, manufacturing teams cannot use solvent in the cleaning and cannot provide the QC [quality control] team with methanol samples,” he specifies. “Other factors such as material cost and reagent toxicity must also be considered.”

Analytical methods should meet detection limit requirements. “Regardless of what the cleaning is, we perform a product-specific validation of the analytical methods, such as TOC [total organic carbon], HPLC, or UV [ultraviolet]. This [product-specific validation] provides the data for the overall process cleaning validation,” continues Goodwin.

Goodwin also points out that analytics ensure cleaning process consistency. “The work instructions are coupled with automation and process analytical technology (PAT) to demonstrate that we are able to remove the previous product from the equipment consistently every time,” he says.

Analytical tools used in cleaning validation include HPLC (limit and quantitate test), gas chromatography (GC), spectrophotometry, TOC, microbial analysis, total protein analysis, and visual inspection. However, the analytical tool used for cleaning validation depends on the product used on the equipment, according to Vengurlekar.

Pre-approved test methods developed for a cleaning activity for a specific product should be compared for every quality control release, Goodwin agrees. “A one-size-fits-all approach is not feasible at BioVectra given the varied product mix,”
says Goodwin.

“For complex chemistry and small molecules, product-specific analytical methods, like HPLC or GC, [are typically used] to detect trace amounts of the intact API. Often this means adapting the release assay method to detect 1000–10,000-fold lower concentrations in the cleaning samples, at levels approaching 1 µg/mL in solution,” says Goodwin. “For biologics, nonspecific methods, such as TOC and conductivity, [are generally applied], which are more appropriate to these sample matrices.”

Data collected from analytical laboratory testing can provide information on method sensitivity and determine recovery for rinse and swab samples, according to Goodwin. Cleaning solvent volumes, temperatures, contact time, and stir rate data can be obtained from production data. Coverage testing on equipment that uses spray balls can determine if there are dead spots, he says.

“The information collected on a given cleaning validation can certainly be used to inform subsequent cleaning activities for other products, though it is important that the development work is sound prior to putting any new product into manufacturing equipment,” Goodwin stresses.

Analytics can be used to develop a cleaning validation procedure and evaluate critical process parameters such as solubility, porosity and roughness, concentration of cleaning agents, water temperature and flow, contact time, and cleaning times, confirms Vengurlekar. “The level of drug product and cleaning agents detected through analytical methods after cleaning can be used to improve the cleaning procedure to ensure residuals/carryover to the next product are within allowable limits and prevent risk to consumers,” he summarizes.

Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients


Vol. 48, No. 1
January 2024
Pages: 26–27

When referring to this article, please cite it as Haigney, S. Proving It’s Clean with Analytics. 

Analytical methods and tools play a pivotal role in cleaning validation.

Proving It’s Clean with Analytics

TOP NEWS on grunge world map | Image Credit: © Sean K - stock.adobe.com

On Dec. 12, 2023, AstraZeneca announced a definitive agreement to acquire Icosavax, a US-based clinical stage biopharmaceutical company focused on developing vaccines using a protein virus-like particle (VLP) platform. The deal represents a value of roughly $800 million upfront, with the potential of $1.1 billion in total. With the acquisition, AstraZeneca will build on its vaccines and immune therapies pipeline with the addition of a potential respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) combination vaccine. 

Icosavax’s lead investigational vaccine candidate, IVX-A12, is a combination protein VLP vaccine that targets both RSV and hMPV. The candidate will be entering Phase III clinical studies. IVX-A12 represents the first combination vaccine for RSV and hMPV, according to a company press release. There are currently no treatments or preventative therapies for hMPV, according to the release.

“This virus-like particle vaccine technology has the potential to transform prevention against severe infectious diseases, including RSV and hMPV. With the addition of Icosavax’s Phase III-ready lead asset to our late-stage pipeline, we will have a differentiated, advanced investigational vaccine, and a platform for further development of combination vaccines against respiratory viruses. This aligns with our strategy to deliver a portfolio of therapies to address high unmet needs in infectious diseases, and our ambition to protect the most vulnerable patients who have high risk of severe outcomes,” said Iskra Reic, executive vice-president, Vaccines & Immune Therapies, AstraZeneca, in the press release.

With the acquisition, AstraZeneca will gain a potential RSV and hMPV combination vaccine.

AstraZeneca to Acquire Icosavax in Deal Valued at Approximately $1.1 Billion 

Cheryl Barton is director of PharmaVision, 

In May 2022, the European Commission (EC) proposed the introduction of a European Health Data Space (EHDS) to improve health democratization in Europe and develop a national infrastructure for health data management, exchange, and sharing (1). Creating a common EHDS was one of the priorities of the EC during 2019–2025, and the proposal builds on the European digital strategy for data, COM(2020) 66 (2), and enables the EC to meet its goals to improve public health, reduce health inequalities, and move towards a more social Europe (3).

EHDS seeks to streamline data access and sharing in the EU

On 13 Dec. 2023, the European Parliament (EP) adopted its position on creating EHDS with 516 votes in favour, 95 against, and 20 abstentions (4). Each country would establish national health data access services based on the MyHealth@EU platform. The law would also set out rules on the quality and security of data for providers of Electronic Health Records (EHR) systems in the European Union, to be monitored by national market surveillance authorities (4). Health data, including EHRs, electronic prescriptions, laboratory results, hospital discharge reports, and patient summaries, would be made available in a common format that could be shared with healthcare professionals and the patient both within and between European countries (5).

The EHDS seeks to address health-specific challenges regarding data access and sharing, which include:

creating rules for making EHR systems available on the EU market

empowering patients with new rights to control their electronic health data in the context of healthcare

establishing mandatory cross-border infrastructure enabling the use of electronic health data across the EU for the primary use purpose of providing health services

introducing obligations on ‘data holders’ to make electronic health data available to third parties, including public sector bodies, for ‘secondary use’, and set out rules and mechanisms to support this (5).

According to the EC, “Citizens should be empowered to make better decisions based on insights gleaned from non-personal data. And that data should be available to all—whether public or private, big or small, start-up or giant. This will help society to get the most out of innovation and competition and ensure that everyone benefits from a digital dividend” (2).

Implication of the EHDS on the pharma industry

The EHDS would enable pharma to gain access to a broader pool of quality data for R&D purposes (5). It should also help to standardize data and would mean that, within the EU, pharma companies would only have to comply with a single set of rules regarding data usage and privacy rather than dealing with multiple sets of regulations. This is important as the current General Data Protection Regulation (GDPR) is unevenly applied and open to interpretation within member states and has created uncertainty and challenges around access and resulted in barriers to the “secondary use of electronic health data” (6).

One key feature of the EHDS that could have a far-reaching impact on the pharmaceutical sector is the proposal to expand the availability of electronic health data for secondary use, such as R&D activities (6). “Data holders”, which include the pharmaceutical, healthcare, and MedTech sectors, may be compelled to allow access to certain categories of data (e.g., health registries and clinical trials). However, access to these data would only be granted where the intended purpose for processing satisfies Article 34(1) of the Proposal, which includes the following criteria:

activities relating to public interest, development, and innovation activities in/contributing to the area of public and occupational health

educational, teaching activities, and scientific research related to health or the care sector

providing personalized healthcare consisting in assessing, maintaining, or restoring the state of health of individuals

ensuring high levels of quality and safety of health care, medicinal products, or devices

testing, training, and evaluating algorithms, including artificial intelligence (AI) systems, digital health applications, and medical devices, contributing to public health or social security (7).

Secondary use of health data would require the data “re-user” to submit an access application, which would then be assessed and permission granted by the competent Health Data Access Bodies (HDAB). Any fees charged by the data holder would have to be transparent, proportionate, and “must not restrict competition.” Where access to data is granted, it must be transferred in an anonymized format unless the applicant’s purpose cannot be achieved by processing anonymized data, in which case pseudonymized data may be provided (7).

The lack of clarity over the protection of data that pharma generates has caused significant uncertainty and is an area that will need to be addressed to ensure the EHDS does not stifle innovation and investment in medical research (6).

In September 2023, the European Federation of Pharmaceutical Industries and Associations (EFPIA) participated in a multi-stakeholder group including patient organizations, industry associations, and EU officials, to discuss the EHDS (8). This followed from a previous meeting in June 2023 where they discussed concerns over an opt-out mechanism that could impact the secondary use of electronic data (9).

In December 2023, EFPIA responded to the EP’s adoption of the EHDS and stated that it “believes that sharing of health data can bring enormous beneﬁts to patients, healthcare professionals, and health systems.” However, “it is concerned about the inclusion of opt-out and opt-in mechanisms or certain categories of data as this will reduce the amount of data ultimately available within the EHDS” (10).

EFPIA is particularly concerned about the impact of EHDS in rare disease R&D where data are scarce and it could further limit the development of personalized/precision medicines. EFPIA would like further clarification and clearer rulings on how the private sector’s intangible assets will be protected. Although the EP has amended the EDHS to include provisions on the protection of intellectual property (IP), it does not fully address how the EU IP framework will coexist with the future EHDS framework and it shifts the responsibility of HDAB to preserve the data holder’s trade secrets, which could cause bottlenecks in the system (10).

The EP is now ready to start negotiations with the governments of EU member states on the final form of the law (1). Meanwhile, EFPIA is keen to work with stakeholders to clearly define the respective rules around the protection of IP rights and Trade Secrets and what is meant by each data type and definitions currently listed for secondary access (10). Further negotiation will be essential to get the balance right and establish a fit-for-purpose, workable ecosystem for health data access and sharing for the future.

1. European Parliament News. EU Health Data Space: Access to Your Health Data Across the EU. 

. Communication Document, 19 Jan. 2020.
3. European Parliament News. Improving Public Health: EU Measures Explained. 

, 10 Oct. 2022.
4. European Parliament News. EP Supports Creating EU Health Data Space to Boost Access to Data and Research. 

, 13 Dec. 2023.
5. Vettorazzi, S. Establishing the European Health Data Space. Initial Appraisal of a European Commission Impact Assessment. European Parliament Briefing, January 2023.
6. McFadyen, A. What the European Health Data Space Means for Pharmaceutical Companies. Pinsent Masons, 

Proposal for a Regulation of the European Parliament and of the Council on the European Health Data Space

. 3 May 2022.
8. EFPIA. EFPIA attends meeting to discuss opt-out requirements in EHDS. Press Release, 6 Sept. 2023.
9. EFPIA. Joint Statement: Health Organisations Define EHDS’ Opt-out Required for Life-Saving Research. Press Release, 6 June 2023.
10. EFPIA. EFPIA Response to EHDS Report Adopted by ENVI/LIBE Committee in the European Parliament. Press Release, 1 Dec. 2023.

Cheryl Barton is director at PharmaVision, Pharmavision.co.uk.


Vol. 36, No. 1
January 2024
Pages: 8–9

When referring to this article, please cite it as Barton, C. Finalizing the European Health Data Space. 

The EHDS aims to increase access to health data, but how will it impact pharma?

Finalizing the European Health Data Space

Retro classic typewriter from circa 1950s with sheet of paper and aged books on wooden desk front aquamarine wall background. Nostalgic writer's work place concept. Vintage old style filtered photo | Image credit: © BrAt82 - stock.adobe.com

Across the Western world, the number 13 is commonly considered to be unlucky; so much so that in many aspects of life, such as hotel floors, aeroplane seat rows, and even house numbers, the use of 13 is avoided completely. Popular theories about the basis for this superstitious belief include the arrival of Judas Iscariot at the Last Supper and the Norse god Loki at a dinner party in Valhalla, as both were the 13th guest, and both are associated with negative outcomes (1).

However, in 2024, for the bio/pharma industry, 13 may prove to be lucky, certainly for the companies whose drugs have been revealed as ‘ones to watch’ in Clarivate’s latest annual report (2). Each year, analysts from Clarivate evaluate drugs in development and discern, using certain factors, which ones they believe will be blockbusters (reaching $1 billion in annual sales) or will be therapeutic game changers.

“The fundamentals underpinning the biopharma sector have never been stronger, with new technologies fuelling medical advancements and providing treatment options to patients with previously unmet needs,” said Mike Ward, global head of Thought Leadership, Life Sciences and Healthcare, Clarivate, in a press release (3). “Leveraging deep industry expertise and comprehensive therapeutic area differentiated data, this year’s 

 report identifies innovative medicines based on recent scientific breakthroughs poised to have extraordinary impacts on patient outcomes.”

From their analysis for 2024, the Clarivate experts created a list of 13 late-stage therapies that cover a wide number of conditions, including breast cancer, multiple myeloma, sickle cell disease, and respiratory syncytial virus (RSV). The ‘Drugs to Watch’ for 2024 are: 

aflibercept (high dose; EYLEA HD)—developed by Bayer and Regeneron Pharmaceuticals Inc. for the treatment of we age-related macular degeneration, diabetic macular oedema, or diabetic retinopathy

budesonide (TARPEYO/Kinpeygo/Nefecon)—developed by Calliditas Therapeutics AB, Everest Medicines and STADA Arzneimittel AG to reduce proteinuria in adults with IgA nephropathy

datopotamab deruxtecan (Dato-DXd)—developed by AstraZeneca and Daiichi Sankyo to treat metastatic non-small cell lung cancer or metastatic HR-positive/HER2-negative breast cancer

efanesoctocog alfa (ALTUVIIIO/BIVV001)—developed by Sanofi (Bioverativ Therapeutics Inc) and Swedish Orphan Biovitrum AB (Sobi) to reduce therapy burden for haemophilia A patients

ensifentrine (RPL554)—developed by Verona Pharma to reduce exacerbations in moderate to severe chronic obstructive pulmonary disease without systemic side effects

exagamglogene autotemcel (CASGEVY/exa-cel)—developed by CRISPR Therapeutics and Vertex Pharmaceuticals Inc. to treat severe sickle cell disease

lovotibeglogene autotemcel (Lyfgenia/lovo-cel/formerly LentiGlobin)—developed by CRISPR Therapeutics and Bluebird Bio to treat severe sickle cell disease and transfusion-dependent beta-thalassemia

mirikizumab (Omvoh/LY-3074828)—developed by Eli Lilly and Company to treat Crohn’s disease and moderately to severely active ulcerative colitis

niraparib + abiraterone acetate (AKEEGA)—developed by Johnson & Johnson Innovative Medicine to treat deleterious or suspected deleterious BRCA-mutated, metastatic castration-resistant prostate cancer

RSVpreF (ABRYSVO/PF-06928316)—developed by Pfizer Inc. as a vaccine to prevent lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV)

RSVpreF3 (AREXVY/GSK-3844766A)—developed by GSK plc as a vaccine to prevent LRTD caused by RSV

talquetamab (TALVEY)—developed by Johnson & Johnson Innovative Medicine to treat relapsed or refractory multiple myeloma

zolbetuximab (IMAB362)—developed by Astellas Pharma Inc. to treat HER2-negative, CLDN18.2-positive unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

If prior year’s predictions and analyses by Clarivate experts are anything to go by, then 13 might very well be considered lucky in bio/pharma for 2024.

Maranzani, B. What’s So Unlucky About the Number 13? 

Clarivate. Clarivate Identifies Thirteen Potential Blockbuster Drugs and Gamechangers in Annual Drugs to Watch Report. Press Release, 8 Jan. 2024.

Clarivate has released its 2024 Drugs to Watch report, highlighting 13 therapies with great potential.

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