Behind the Headlines Episode 27

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

Artificial intelligence, machine learning, and novel instruments are helping drug developers.

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

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? 

Articles

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.

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

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.

1. UK Gov. The Innovative Devices Access Pathway (IDAP)–Pilot Phase. 

 Updated 29 Feb. 2024.
2. HM Government. 

. Report, July 2021.
3. MTRC Consulting. The Pilot Phase of the Innovative Devices Access Pathway Launched in the UK. News Release, 25 Sept. 2023.
4. UK Gov. IDAP Pilot Application Guidance (now closed). 

 19 Sept. 2023.
5. HGF Intellectual Property News. The Innovative Devices Access Pathway (IDAP). News Release, October 2023.
6. Gemmell, E. IDAP Pilot: A Welcome Post-Brexit Move. 

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

When referring to this article, please cite it as Piachaud-Moustakis, B. Improving Patient Access Through the UK IDAP Scheme. 

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.

Improving Patient Access Through the UK IDAP Scheme

Feliza Mirasol is the science editor for 

Considerations for the Use of Human- and Animal-Derived Materials and Components in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products

, has been made available for public comment by FDA (1). FDA’s Center for Biologics Evaluation and Research issued the draft document in April 2024.

In the draft guidance, manufacturers of cellular and gene therapy (CGT) and tissue-engineered medical products (TEMPs) are provided recommendations for assuring the safety, quality, and identity of materials—both human and animal origin—that are used to manufacture CGTs and TEMPs. Recommendations are given in regard to the chemistry, manufacturing, and control (CMC) information related to the use of human- and animal-derived materials. This type of information is submitted for an investigational new drug application.

Materials covered by this draft guidance include the reagents, feeder cells, excipients, and other inactive ingredients in the drug product that are in direct contact with the starting material, intermediates, and final products as well as any materials used to manufacture reagents, feeder cells, and excipients, and materials incorporated in TEMPs, according to FDA (1). Materials excluded from the guidance include human cells used as starting material to manufacture human cells, tissues, and cellular and tissue-based products, including TEMPs.

The agency states in the document that “Use of human- and animal-derived materials during product manufacturing may increase risks of infectious disease transmission, and raises potential safety concerns, such as the possible introduction of adventitious agents or other impurities into CGT products and TEMPs. Thus, human- and animal-derived materials should be thoroughly characterized and described in your regulatory submission” (1).

Comments can be submitted electronically or in writing by the deadline date on July 29, 2024, after which time, the agency will begin working on a final version of the guidance (2).

According to the agency, this guidance is intended to supplement the two final industry guidance documents, 

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) 

Draft Guidance for Industry, Considerations for the Use of Human-and Animal-Derived Materials in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products

Considerations for the Use of Human-and Animal-Derived Materials and Components in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products; Draft Guidance for Industry; Availability

Guidance for Industry, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

. Guidance for FDA Reviewers and Sponsors, Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)

A new draft guidance issued by FDA covers human- and animal-derived materials used in the manufacture of advanced therapy medicinal products.



New FDA Draft Guidance Made Available for Materials Used in Manufacturing CGTs and Tissue-Engineered Therapeutics

Communication between the manufacturing plant and retail stores. | Image Credit: © Cagkan - © Cagkan - stock.adobe.com

Cormica, a UK-based medical device and pharmaceuticals testing group, announced on May 1, 2024 that it has completed its seven-figure acquisition of TPM Laboratories (TPM), an independent contract testing laboratory based in New Jersey. Cormica is backed by Limerston Capital, a UK mid-market private equity investment firm, and is focused on expansion across the United States and Europe. According to Cormica (1), the deal is intended to use Cormica’s expertise and broad service line to help TPM grow organically and reach its full potential.

TPM provides analytical services to the pharmaceutical and chemical industries, such as quality control, research and development, and stability storage and testing services. Its facility is 8000 sq ft of office and laboratory space and can handle anti-cancer products. Rupa Iyer, president and founder of TPM, will continue to lead TPM’s US team with support from Cormica.

“The acquisition marks a milestone moment for Cormica and clearly demonstrates our ambitions to grow our international footprint and increase our market share in a highly competitive market,” said Mark Hammond, Cormica Group CEO in a press release (1). “TPM boasts a highly skilled laboratory team with extensive pharmaceutical experience which has helped it to build a strong reputation for excellence. We are looking forward to working with Rupa and her team as we explore how we can help support the expansion of the business and use it to further our aims in the US, both organically and via further acquisitions.”

“I am proud of the success TPM has had to-date, but I also recognise that the business has the ability to scale-up,” Iyer added. “Cormica has a compelling offer, driven by people who understand the industry and how to create opportunities. This marks a new chapter in our story, and we are keen to work more closely with our colleagues in the UK and Europe.”

Cormica recently expanded its own testing facilities in January 2024, with an expansion to its Cormica Bradford division. The expansion added two Agilent 1260 Infinity II LCs (liquid chromatography) to the company’s suite of high-performance liquid chromatography instruments. Cormica also upgraded its particle size distribution analysis capabilities with the Microtrac S3500 Laser Diffraction power spectral density instrument, which was equipped with both wet and dry dispersers, joining the company’s range of particle size analyzers. Finally, the company added the Copley JVT100i Tapped Density Tester to bolster its powder density testing capabilities.

In a press release on the expansion, Caroline German, technical director at Cormica, said, “By expanding our equipment range and updating our capabilities, we’re not just enhancing our capacity; we’re aligning more closely with our clients’ hardware and methodologies. This streamlines the method development, validation, and transfer process, allowing for more efficient and seamless service delivery.”

Limerston Capital Backed Cormica Announces First US Acquisition With New Jersey Based TPM Laboratories

Cormica Bradford Expands Testing Capabilities with State-of-the-Art Equipment

Cormica’s first US Acquisition is intended to support to organic growth of TPM laboratories.

Cormica Announces Seven-Figure Acquisition of TPM Laboratories

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

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

On 6 May 2024, the King’s Awards for Enterprise 2024 winners were announced and included pharmaceutical company, Nanomerics, and several companies that provide services to the pharmaceutical industry. The awards (previously known as the Queen’s Awards for Enterprise) recognize outstanding achievements in enterprise across four categories: innovation; international trade; sustainable development; and promoting opportunity (through social mobility) (1).

Nanomerics, a spin-out from University College London, received the King’s Award for Enterprise in the category of Innovation. The company has been recognized for its active excipient platform for precision medicines, Molecular Envelope Technology (MET). MET works by encapsulating nano-scaled drug doses and allowing water-insoluble compounds to pass through mucosal barriers, which increases efficacy of the drug product and reduces side effects (2).

“It is a real honour to win the King’s Award for Enterprise 2024 in the Innovation category,” said Professor Andreas G. Schätzlein, CEO of Nanomerics, in a press release (2). “This award recognizes the efforts we are making to ensure that drug development has a higher likelihood of success.”

However, the majority of the winners from the pharma industry for 2024 have been recognized for their achievements in international trade. Gentronix, for example, which is a contract research organization that specializes in toxicology, received the award as a result of achieving triple-figure revenue growth thanks to its international expansion (3); and, Seda Pharmaceutical Development Services, which works with biotech companies to help design, develop, and market novel medicinal products, was recognized for its “outstanding short-term growth in overseas sales” (4).

Furthermore, several consulting groups were also recognized in this year’s awards for their successes in international trade. Among these groups were Uptake Strategies, which is a global healthcare consultancy for the pharma and biotech industry (5); and DLRC, which is global consultancy providing regulatory services to pharma and medtech companies of all sizes (6).

The full list of winners for 2024 can be found in a 

1. The London Gazette. The King’s Awards for Enterprise. 

 (accessed 13 May 2024).
2. Nanomerics. Nanomerics Wins the United Kingdom King’s Award for Enterprise 2024. Press Release, 6 May 2024.
3. Tate, M. Genotronix Recognized with King’s Award After Record International Growth. Press Release, 7 May 2024.
4. Seda Pharmaceutical Development Services. Stockport Based, Seda Pharmaceutical Development Services Wins King’s Award for Enterprise 2024. Press Release, 6 May 2024.
5. King, C. Uptake Honoured in the King’s Awards for Enterprise 2024. Press Release, 6 May 2024.
6. DLRC. DLRC Achieves King’s Award for Enterprise in International Trade. Press Release, 6 May 2024.
7. The London Gazette. The King’s Awards for Enterprise. 

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.

When referring to this article, please cite it as Thomas, F. Streamlining Variations. 

Pharmaceutical company, Nanomerics, and several companies that work with the pharmaceutical industry have been recognized by King Charles III for business achievements.

Royal Recognition

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

Santander UK, a retail and commercial bank based in the United Kingdom, has announced it has provided Ennogen Healthcare International, a UK-based pharmaceuticals manufacturer, with a £30 million loan to support its international expansion plans. Ennogen, which was established in 2011, is focused on dermatology, respiratory, and pain relief therapies, especially those with chronic conditions. The loan package is intended to support the company’s rapid growth as it invests in purchasing bolt-on pharmaceutical products in appropriate therapeutic areas and targets future acquisitions. The approved funding may be extended to £50 million as Ennogen considers international expansion opportunities, although this is subject to future approvals.

“Santander quickly understood our business and came up with an innovative and flexible approach to meet our acquisition and product development needs,” said Jason Tate, chief financial officer at Ennogen, in a Santander press release (1). “With offices and specialism in key locations around the world, Santander are best placed to support our international expansion strategy. Working with both the team in Manchester and Liverpool, it is clear they have a strong knowledge of the pharmaceutical and healthcare industry.”

Ennogen is based in Dartford and has a regional office in Northwich, Cheshire. Over the past few years, it has grown both organically and through acquisitions, resulting in its current staff totaing over 50 members. Its growth so far has been funded through cashflow and shareholder injections; this loan is intended to give the company a flexible approach to its growth strategy.

“We are delighted to support Ennogen with this new £30m facility, which will help deliver their acquisition plans,” said Sarah Laverty, Structured Finance director at Santander UK in the press release. “The business has a strong management team and clearly articulated strategy, which is exactly the type of business Santander looks to support.”

Santander Provides Pharma Manufacturer Ennogen with £30 Million Credit Facility for Growth

The loan is intended to support Ennogen’s growth as it looks to international acquisitions.

Santander UK Grants £30 Million Loan Package to Ennogen Healthcare

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

In this video, Chris Spivey, Director, Industry Relations and Strategic Partnerships, talks with industry experts about aspects of drug product stability.

Drug Digest: Is Our Understanding of Stability Changing

In this exclusive Drug Digest video interview, Chris Spivey, Director, Industry Relations and Strategic Partnerships, interviews Nitin Swarnaker, Pharma Applications Manager, BASF, and Geoff Carr, Former Director, Analytical Development, Thermo Fisher Scientific/Patheonabout various aspects of drug product stability testing. Stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. Over the last decade there has been some intermixing of supply chain storage and distribution systems, and traditional formulations taking these storage and delivery systems into account—continuous monitoring comes to mind. While long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% RH ± 5% RH or at 30 °C ± 2 °C/65% RH ± 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 °C ± 2 °C/65% RH ± 5% RH. Accelerated Predictive Stability (APS) studies, carried out over a 3–4-week period and combining extreme temperatures and RH conditions (40–90 °C)/10–90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner.

Nitin is a Formulation scientist with over 16 years of combined (academic research/training/industrial) experience, and a very strong track record of publications, primarily focused on various formulation aspects of small, peptide and protein molecules for oral and parenteral applications. He has vast experienced in solid, solution, suspension, semisolid products and novel drug delivery systems such as lipid- and polymer-based drug delivery systems (proliposomes and liposomes, liquid crystalline particles nanoparticles and microspheres) including their targeted drug delivery counterparts. He is well-versed in various characterization techniques used in formulation development, possesses a good understanding of various regulatory guidelines and cutting edge concepts and technologies.

Former Director, Analytical Development, Thermo Fisher Scientific/Patheon

Geoff Carr, PhD, has retired after over 45 years experience of working in the pharmaceutical industry and currently provides training and consultancy services to pharmaceutical companies with an emphasis on the application of good chemistry in the development of new pharmaceutical products. Previously, he was appointed as Manager, Analytical Development at Patheon Inc, Canada in 2000 and progressed to Director, Analytical Development, Thermofisher Scientific/Patheon until 2023. Prior to that, he held positions of Manager, Analytical Sciences at Celltech-Chiroscience, UK, Head of Analytical Development at Medgenix, Belgium and before that at Wyeth Research, UK. He originally started his career in pharmaceutical analysis at The British Pharmacopoeia Laboratory where he held several posts and was finally appointed Head of the Laboratory. His academic background is a PhD in synthetic organic chemistry awarded by University of London, UK. He has been a member of various British Pharmacopoeia Committees, a UK representative to Committees of the European Pharmacopoeia and Member of USP Committees including a Member of the 2015-2020 Cycle USP General Chapters – Physical Methods Expert Committee. He is the author of numerous publications including journal articles and book chapters as well as presentations and workshops at international conferences on various topics related to applications of analytical chemistry during the development of pharmaceutical products. This includes a 8 module distance learning course on Pharmaceutical Stability Testing.

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

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

 Biologic Drug Development and Manufacturing

Videos

In this exclusive Drug Digest video interview, Chris Spivey, Director, Industry Relations and Strategic Partnerships, talks with industry experts about various aspects of drug product stability testing.

Mike Hennessy Jr. is the Chairman and CEO of 

High Angle Shot of a Working Desk of a Successful Person in Office with Cityscape Window View. | Image credit: © Gorodenkoff - stock.adobe.com

Research efforts are continuing to expand in the area of biological therapies. These large-molecule drugs are proving to be significant revenue drivers for bio/pharma companies and are providing therapeutic options for disease areas that have previously suffered from unmet medical needs (1).

Additionally, biologics are useful in providing more targeted disease treatment when compared with small-molecule drugs and lessening the risk of side effects for patients. The targeted nature of these large-molecule therapies is explored in this issue’s cover story, featured on pages 10–13, along with the potential that technological advances hold in pushing future boundaries and some of the challenges facing both the development and manufacture of biologic drugs (2).

Advanced therapy medicinal products (ATMPs), which are promising and often curative biologic therapies, face their own specific development and manufacturing challenges. Scalability of manufacturing for these emerging therapies is a particular bottleneck and something that San Francisco-based Cellares, a self-titled integrated development and manufacturing organization (IDMO), has sought to change. In an interview with Pharmaceutical Technology® Group, Fabian Gerlinghaus, CEO and co-founder of Cellares, detailed how the company’s Cell Shuttle platform and integrated consumable cartridge automated platform can improve scalability of ATMP manufacturing (3).

The IDMO has also garnered interest from Bristol Myers Squibb (BMS), which joined the Technology Adoption Partnership (TAP) program in August 2023 (4). Participation in the TAP program has meant that BMS can use Cellares’ automated manufacturing platform for the manufacture of its pipeline products.

Most recently, in April 2024, BMS and Cellares built upon their relationship by entering into a deal worth $380 million, where Cellares will transfer select chimeric antigen receptor T-cell therapies onto its manufacturing platform, with the aim of meeting growing demand and improving turnaround time (5).

1. Bender, M. Pharmaceutical & Life Sciences Trends 2024. 

 (accessed April 24, 2024).
2. Thomas, F. Biologics On Target for the Future. 

, 48 (5), 10–13.
3. Spivey, C. Cellares Innovates with Automated Cell and Gene Therapy Platform. 

, March 7, 2024.
4. Cellares. Cellares Announces Bristol Myers Squibb has Joined Technology Adoption Partnership Program to Evaluate Automated Manufacturing of CAR-T Cell Therapy on the Cell Shuttle Platform. Press Release, Aug. 28, 2024.
5. Cellares. Bristol Myers Squibb and Cellares Announce a $350M Worldwide Capacity Reservation and Supply Agreement for the Manufacture of CAR T Cell Therapies to Bring the Promise of Cell Therapy to More Patients, Faster. Press Release, April 22, 2024.

Mike Hennessy Jr. is the President and CEO of 

When referring to this article, please cite it as Hennessy, M. Tapping into the Potential of Biologics. 

Technological advances are helping advance biologics development and manufacturing and reduce bottlenecks.

Tapping into the Potential of Biologics

FDA’s Center for Drug Evaluation and Research (CDER) has published the 2023 Office of New Drugs (OND) Annual Report. The report details the office’s major achievements of 2023, including notable drug approvals, publications, guidances, workshops, webinars, and meetings. Specifically, these achievements contain over 3400 formal meetings between sponsors of new drug development programs and CDER staff; 25 public Advisory Committee meetings; 55 novel drug approvals; 34 issued guidances; 651 OND speaking engagements; and OND representations at meetings, including Patient-Focused Drug Development meetings, Critical Path Innovation meetings, and Patient Listening Sessions.

Also featured are innovations in drug design and development, as well as OND’s partnerships with FDA and external stakeholders to tackle obstacles in drug development and regulation. The report demonstrates OND’s efforts in supporting drug development, pushing forward important drug approvals through substantial application reviews, using workshops and new guidances to promote policy, and maintaining careful post-approval drug assessments.

The report is largely divided into individual office reports, including the offices of: cardiology, hematology, endocrinology, and nephrology (OCHEN); drug evaluation sciences (ODES); immunology and inflammation (OII); infectious diseases (OID); neuroscience (ON); nonprescription drugs (ONPD); oncologic diseases (OOD); rare diseases, pediatrics, urologic and reproductive medicine (ORPURM); specialty medicine (OSM); therapeutic biologics and biosimilars (OTBB); and the non-clinical offices of program operations (OPO), regulatory operations (ORO), administrative operations (OAO), and new drug policy (ONDP). Each section includes a brief overview of the department, followed by its major achievements from the year. The report also features a message from the director, OND’s senior leadership team, an organizational chart of the office, publications from each office, and a list of acronyms and key terms.

Over 2023, OND organized 21 patient listening sessions, 18 of which were organized with the office of the commissioner and the office of patient affairs, and 3 of which were organized with professional affairs and stakeholder engagement. OND’s drug approvals in 2023 included new molecular entity (NME) new drug applications (NDAs), and biologics applications (BLAs), with additional efficacy supplement approvals and approvals to breakthrough therapy requests and fast track requests.

“This report documents the diverse efforts of OND staff, beyond the regulatory actions to approve important drugs,” stated Peter Stein, Director, Office of New Drugs in the report (1). “These efforts include holding many public meetings both to inform our OND staff of cutting edge science, and for OND staff to contribute to the knowledge of those in the pharmaceutical industry, in academics, and for patients and other stakeholder groups about advances in regulatory science, the biology of disease, and advances in clinical drug development; publishing numerous guidances that give insight to drug developers about the pathways and approaches to development that can provide the data FDA needs to support the effectiveness and safety of new drugs; the careful monitoring of drug safety post-approval to assure that drug’s prescribing information is kept updated with the safety information that health care practitioners and patients need.”

Center for Drug Evaluation and Research (CDER), 

2023 OND Annual Report: Breaking Barriers to Advance Public Health

The report covers the major achievements of the office during 2023, including notable drug approvals, publications, guidances, workshops, webinars, and meetings.

CDER Releases Office of New Drugs 2023 Annual Report

Siegfried Schmitt, PhD, is Vice President Technical at Parexel International, Siegfried.Schmitt@parexel.com.

Q: We read in an article (1) that there are no specific good manufacturing practice (GMP) regulations for emerging therapies in the United States, yet we wish to bring our emerging therapy products to the US market. How can we make sure our products comply with current regulations?

A: In the absence of specific regulations for your products, the existing generic regulations, such as 21 Code of Federal Regulations (CFR), 600 Biological Products (2), will apply as appropriate. Also, international harmonized guidelines, such as International Council for Harmonisation (ICH) Q9(R1) Quality Risk Management and ICH Q10 Pharmaceutical Quality System (3,4) need to be followed and complied with. However, these are not the only sources of regulatory information available. FDA has published guidance on cellular and gene therapy products (5), which includes guidance and information on “Regenerative Medicine Advanced Therapy Designation” and on “Interactions with Office of Tissues and Advanced Therapies”.

Companies, especially developers of new types of drugs, are encouraged to interact with the regulatory authorities early on in the drug development cycle, and FDA is no exception. There are multiple opportunities for formal as well as informal meetings with FDA, and FDA’s website provides an excellent overview, including links to further information (6).

There is more information out there, free of charge, and most likely relevant to the products your company is currently developing. Though international regulations are only harmonized to some degree, there is generally a broad consensus on the basic principles of GMP, be it for traditional drug products or novel, emerging therapy products. Therefore, companies should look at regulations from other regions (e.g., the European Union [EU]) and guidance from key agencies, such as the European Medicines Agency (EMA). The EU have issued specific regulations for advanced therapy medicinal products (7), recognizing the need to address compliance for these products separately. The GMP requirements detailed in here will broadly be the same that FDA expects. Aspects that require further guidance and clarification are often covered in “Questions & Answers” documents published by EMA. An EMA Q&A document published in 2011 (8) discusses, for example, how to identify the minimum GMP requirements for starting materials, considering quality management, quality risk management, product development, production, and quality control.

These are just a few pieces of information in response to your question. There is much more information available online, from specialist publications, subject matter experts, and not least directly from the regulatory agencies through their consultation mechanisms.

Thomas, F. Optimizing the Manufacture of Emerging Therapies. 

FDA. Interactions with Office of Therapeutic Products. 

EC. Part IV, GMP requirements for Advanced Therapy Medicinal Products. 

Questions and Answers on the Principles of GMP for the Manufacturing of Starting Materials of Biological Origin Used to Transfer Genetic Material for the Manufacturing of ATMPs,

When referring to this article, please cite it as Schmitt, S. GMPs for Emerging Therapies.

Guidance documents and interaction with FDA can help manufacturers stay in GMP compliance, says Siegfried Schmitt, VP Technical, at Parexel.

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