Summary: Denise Sutton, Chief Operating Officer and Site Head at Quotient Sciences, Nottingham, UK, discusses the site's evolution and its role in integrated drug development. She reflects on the site's legacy, its expansion in capabilities, and the collaborative culture that drives innovation. Denise emphasizes the importance of customer-centricity, operational excellence, and team empowerment in delivering high-quality pharmaceutical solutions that support global patient needs.

Quotient Sciences – Nottingham offers our clients a powerful combination of drug development capabilities and phase 1 expertise underpinned by a strong scientific heritage.

This facility was the origin for Quotient Sciences’ Translational Pharmaceutics® platform, a unique offering not seen elsewhere in the pharma services sector combining on-demand GMP drug product manufacturing with healthy volunteer clinical trials in an integrated program of work led by a single project manager (PM). 

Designed to disrupt conventional drug development industry siloes to achieve significant time and cost efficiencies, Translational Pharmaceutics® is unparalleled in how it helps advance the next generations of medicines to market.  

In our two-part spotlight, we speak with Denise Sutton, Chief Operating Officer and Site Head for our Nottingham, UK facility, about her background, the evolution of the Nottingham facility, and the Translational Pharmaceutics® platform. 

Tell us about your background and how it led you to your current role at Quotient Sciences.

I joined the Nottingham site back in 1999 when the business was Pharmaceutical Profiles, a spin out from the University of Nottingham.  

I had completed my Ph.D. and post-doc in Biochemistry and was attracted by the novel science emerging from Nottingham under Dr. Ian Wilding, Dr. Steve Newman, and Professor Bob Davis. This team was helping drug development experts diagnose challenges in getting their product to the right location, at the right time, and at the right concentration. They were deploying gamma scintigraphic imaging studies to understand how drugs performed in humans under the banner that “a picture tells a thousand words.” It was ground-breaking science, and I joined initially as a Project Leader to help customers manage their programs on challenging molecules. This was a hands-on role in which I gained experience in drug product manufacturing, clinical activities and data analysis/reporting. There’s no better way of getting to know a business and I learned so much!

Since then, I’ve held many roles within the company spanning operations, project management and commercial. I feel extremely lucky to have been given so many learning opportunities and to have gained such a deep understanding of how these typically disparate activities can be integrated in a way that has a very positive impact for our clients’ programs.  

How has the Nottingham site transformed from when you first started to what it is today? 

We were a small company with fewer than 50 employees, a 10-bed clinic, and a single lab. Over 90% of our work focused on gamma scintigraphic imaging. Due to the short half-life radionuclides we used to label dosage forms, every product we manufactured had a limited time to be dosed.  

At the end of 1999, we moved our headquarters to a purpose-built, two-story facility—now known as Trent House on our now much larger Nottingham campus. We built three GMP manufacturing suites on the top floor and three clinical wards on the bottom floor. In effect, this was the very early start of our Translational Pharmaceutics® platform.

We continued to expand the range of scintigraphy applications we offered in response to changing customer requirements until, in 2008, we approached the MHRA with a new request. We asked if it might be possible to work at the same pace as we did in our scintigraphic imaging studies but do so for conventional drug development, without the radiolabel. We explored the application of ICH Q8 Quality by Design (QbD) guidelines to introduce a compositional design space into the CMC section of our regulatory dossier. This officially created a methodology for applying the Translational Pharmaceutics® platform, and we haven’t looked back since.  

Today, our Nottingham site has expanded to a campus of five buildings. We have development and analytical labs, six GMP suites, six clinical wards with a total of 85 beds where we conduct healthy volunteer Phase I clinical studies, and many talented colleagues covering our spectrum of CRO and CDMO services.  

What has remained unchanged all these years is that Translational Pharmaceutics® is our flagship platform for drug development that empowers our clients with unparalleled flexibility.  

We apply Translational Pharmaceutics® across three core applications: first-in-human clinical studies, drug product optimization programs through rapid formulation development and clinical testing, and human ADME programs. No matter how a client chooses to work with us to apply Translational Pharmaceutics®, the benefits of using a single organization and project management team to integrate services lets our clients remain in control and one step ahead of emerging data that impacts the success of their molecule.  

As a leader at Quotient Sciences, what does a typical day look like for you? 

No two days are the same which keeps life interesting.  

Quotient Sciences is a scientifically rich, customer-responsive organization. We know that great service starts with listening to our customers and having great people with a strong team ethic to respond rapidly to the changing demands of early phase research. I therefore ensure much of my time is spent listening to customers, connecting with our project teams and challenging how we can continually improve to find time and cost savings for our customers.

What would you say are the key strengths of the Nottingham site, and how do you support customer programs? 

We’ve discussed Nottingham’s capabilities and strengths of Translational Pharmaceutics®, but I haven’t yet spoken about our project management team.

Nowhere else would a single PM oversee such a broad spectrum of activities, let alone be expected to ensure seamless, timely progression across functions that in any other company would be delivered from within multiple operating areas (in larger CDMOs and CROs) or through using a combination of 3rd party vendors.  

Challenges will arise, but working with the project team, the PM works to anticipate, avoid, and mitigate any impact whenever necessary. We know that time is incredibly valuable for our customers, so the project Gantt chart is our PM team’s guiding light. I believe our PM team is truly world-leading; they communicate well, show great compassion, and lead with integrity.  

I’m super proud of our high-performing, supportive, cross-functional teams that support our customers when they trust their molecules to us, working collaboratively to deliver the best possible service. After 25 years at Quotient, I still really enjoy going to work. I am indebted to my many colleagues for helping me continue to feel like this. 

For more information about Translational Pharmaceutics®, John McDermott, VP of Scientific Consulting, explains how the platform works in a recent video.

Read part two of our interview with Denise

In the next part of this two-part series with Denise Sutton, we discuss highlights of Quotient Sciences’ clinical pharmacology offering, and how we work with our clients to design the best program for their needs. Read the second part of this series.

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Summary: We explore the growth of GLP-1 agonists, what they are, how they work and their benefits, and how Quotient Sciences are helping companies tackle challenges in the development of these therapies, including oral formulations. GLP-1 agonists, originally developed for Type 2 diabetes management, have shown promise in treating obesity and other metabolic disorders. While traditionally administered via subcutaneous injection, efforts are underway to develop oral formulations to improve patient compliance. 

The surge in demand for GLP-1 agonist therapies will boost the biotech sector, driving innovation and growth in the years to come. 

In the United States alone, it is projected that the number of GLP-1 users will hit 30 million by 2030, or approximately 9% of the U.S. population, according to data collected by J.P. Morgan Research. ¹ This rise in demand reflects the growing global challenge of managing chronic metabolic conditions such as diabetes and obesity.

The Centers for Disease Control and Prevention (CDC) estimates that the prevalence of obesity in the U.S. has grown from 30.5% in 1999–2000 to 41.9% in 2017–2020². On a global scale, obesity has more than tripled since 1975.³  

The need for more effective treatments that improve patient outcomes and adherence is growing. Ten GLP-1 agonist drugs, including semaglutide (RYBELSUS®, Ozempic® and Wegovy®) and tirzepatide (Mounjaro® and Zepbound®) have already received FDA approval for managing Type 2 diabetes and weight loss. In an increasingly competitive space, companies are looking for alternative and more patient-friendly methods to administer these therapies other than by subcutaneous (SC) injection.  

In this article, we explore the growth of GLP-1 agonists, what they are, how they work and their benefits, and how Quotient Sciences are helping companies tackle challenges in the development of these therapies, including oral formulations. For more insight, be sure to sign up for email news and updates from Quotient Sciences.

What are GLP-1 agonists and how do they work? 

GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide) are key incretin hormones involved in regulating glucose metabolism. Both are produced in the gastrointestinal tract in response to food intake, specifically glucose and fats. 

When a person consumes food, GLP-1 is released from the intestines into the bloodstream, where it performs several key functions. It signals the pancreas to produce insulin, which helps lower blood sugar levels, and simultaneously tells the liver to reduce glucagon secretion, a hormone that typically raises blood sugar levels. The incretin analogues mimic the action of the naturally occurring hormones, but have been designed to be more potent and longer circulating.

Another function of GLP-1 is its ability to slow gastric emptying. By delaying the passage of food from the stomach to the small intestine, GLP-1 ensures that glucose is released into the bloodstream more gradually, preventing sharp spikes in blood sugar levels. It is also known that GLP-1 has a direct effect on reducing appetite via receptors in the brain. 

What conditions do GLP-1 agonists treat?

In recent years, much attention has been placed on the use of GLP-1 agonists as a treatment for obesity. Research from Harvard Medical School indicates that newer generations of GLP-1 agonists can achieve an average weight loss of 15–25%, significantly surpassing the efficacy of earlier treatments.⁴ 

As research in this area continues, the industry is seeing that GLP-1s can offer significant benefits for patients, beyond blood sugar control and weight loss. 

For example, large-scale cardiovascular outcome trials (CVOTs) have demonstrated that GLP-1 receptor agonists (GLP-1RAs) can significantly reduce the incidence of major adverse cardiovascular events, including heart attack and stroke. GLP-1 drugs have also shown recent potential in protecting kidney function, as evidenced by their ability to reduce albuminuria and slow the decline of the estimated glomerular filtration rate (eGFR), a critical indicator of kidney health.

Despite benefits, like all drugs, GLP-1 agonists are not without side effects, such as nausea and vomiting, which tend to subside over time.³

Are oral solid dose formulations the future of GLP-1 therapies?  

Typically, most approved peptide-based medicines are administered via injection, which may be a drawback for some patients. Maximizing systemic absorption and achieving therapeutic drug levels of a peptide following oral administration is a challenge for drug developers due to degradation in the digestive tract and low, and often variable, absorption. Addressing these problems is crucial as research progresses from preclinical to clinical stages.  

Following decades of research in both academia and industry, innovations in peptide chemistry and drug delivery are enabling more peptides to be optimized for oral administration, making it easier for patients to start and continue their treatment. In addition a number of small molecular weight compounds targeting the GLP-1 receptor are in development and the availability of oral alternatives is likely to significantly change the therapeutic landscape.

Quotient Sciences' capabilities in GLP-1 development 

As the scope of GLP-1 agonists continues to expand, their therapeutic potential is evident, opening new avenues for pharma and biotech companies and their outsourcing partners to explore. 

In clinical trials, the effects of combining GLP-1 agonists with other compounds to act synergistically is being investigated, presenting an exciting opportunity for innovation, enhanced efficacy, and broadened therapeutic applications. At Quotient Sciences, we can help make this process smoother with our integrated clinical pharmacology programs. From early drug development to Phase I trials, we provide the insights and support you need to make critical decisions faster and more effectively. 

Quotient Sciences' drug product formulation development, oral peptides and oral drug delivery expertise including extensive oral peptide experience can help your company harness the full potential of your molecule. 

References:

1. https://jpmorgan.com/insights/global-research/current-events/obesity-drugs
2. https://ncbi.nlm.nih.gov/books/NBK551568
3. https://mayoclinic.org/diseases-conditions/type-2-diabetes/expert-answers/byetta/faq-20057955#:~:text=Doctors%20do%20know%20that%20GLP,longer%2C%20so%20you%20eat%20less
4. https://health.harvard.edu/staying-healthy/glp-1-diabetes-and-weight-loss-drug-side-effects-ozempic-face-and-more 

Ozempic®, Wegovy®, and RYBELSUS® are registered trademarks of Novo Nordisk A/S.

Mounjaro® and Zepbound® are registered trademarks of Eli Lilly and Company. 

Bethanne Lee is a Project Manager working with our Miami, FL and Philadelphia, PA facilities. 

In her role, she helps streamline the implementation of Translational Pharmaceutics® programs in the US. She shares more about her role with Quotient Sciences and day-to-day in this interview. 

“The business lives by its manifesto, which is another aspect I like about working at Quotient Sciences. Decision-making is built around this, our culture fosters this, and our efforts in innovations are piloted by this.”

-Bethanne Lee

What does a project manager do at Quotient Sciences?  

In my role as a project manager at Quotient Sciences, my responsibility is to ensure the successful delivery of projects within set timelines, budget, and quality standards. A crucial part of my role involves leading and coordinating project activities with both my project team and the customer’s team to ensure seamless collaboration.

Describe a typical day in project management at Quotient Sciences.

Any typical day in project management can include preparing for upcoming customer meetings, issuing minutes, finishing follow-up activities from previous customer meetings, and meeting internally to track important activities within the project team. As a project manager, we work internally to find de-risking measures for the program, resolutions to any unforeseen issues that have arrived, and making decisions to progress a customer’s program. From time to time, project managers also support writing change orders.

How has your career at Quotient Sciences progressed?  

The Philadelphia site was previously QS Pharma and was acquired by Quotient Sciences in 2017. At this time, I was a financial analyst working part-time and previously held full-time positions as a laboratory scientist and business development manager since 2004.  

In 2020, I applied for and accepted a full-time position as a client services associate. This role had a global reach where our department supported services across all of Quotient Sciences’ sites in the UK and US. This role enabled me to expand my knowledge from drug product development and manufacturing to other areas of pharmaceutical development such as clinical pharmacology, bioanalysis, 14C ADME studies, and drug substance synthesis and manufacturing.  

In 2022, a project management position opened at the Philadelphia site. With previous technical, sales, and key account experiences, I wanted to take this knowledge and apply it to successfully manage projects. I was eager to do so with a passion for customer and team interactions that foster a healthy teamwork environment.

What experience did you have before you started in your role?

I’ve been with Quotient Sciences since 2004, after graduating from the University of Delaware with a Bachelor of Science degree in Laboratory Science. Prior to Quotient Sciences’ acquisition of QS Pharma in 2017, I held roles as an analytical scientist, project coordinator, business development manager, and financial analyst.

Did you require any qualifications for the role you applied for?  

I joined Quotient Sciences after graduating with my Bachelor of Science degree. In later roles with the company, I went on to obtain a Master of Science degree in Biomedical Science & Engineering from Drexel University and an MBA from Wesley College. These qualifications, congruent with experience in pharmaceutical development from a contract development and manufacturing organization (CDMO) perspective over the course of many years, have been very beneficial for the project manager role.

What learning or qualifications have you gained in this role?

In a typical drug product CDMO setting, a project manager might manage early-stage programs (Phase I and II), late-stage programs (Phase III, registration, validation, commercial), or be able to see a project through the whole process. Here, I have had the opportunity to manage our Translational Pharmaceutics® programs, a platform that touches all stages and truly lives our manifesto: Molecule to Cure. Fast. 

What is unique about Translational Pharmaceutics® is the real-time, adaptive, clinical manufacturing at our Philadelphia site based on emerging clinical data between cohorts, regimens, or periods being conducted at our clinic in Miami. In this setting, we learn the clinical pharmacology aspects of clinical trials and partner very closely with our clinical team throughout the project to manufacture and release the clinical supply for each dosing.

What do you enjoy most about your role?

A project manager is involved in various aspects of the business, which is what I find most enjoyable. They have a broad understanding of the operations and procedures across different departments, which is crucial for the success of a project. Additionally, they have financial responsibilities and must possess or be able to develop a strong business acumen, including the ability to effectively communicate with different teams.  

What aspects do you find most challenging?  

During some aspects of a program, an important activity or milestone may rely on individuals or departments that are not aware of the objectives of the project. The importance of meeting the milestone is, therefore, not an accountable action. This is what I find most challenging. Sometimes this is anticipated, making it crucial to be a step ahead and work with those individuals or departments so they also understand the objectives that the team is working towards. Sometimes this is not anticipated, making timely and effective communication key in bringing everyone on board with the goals the team is putting their efforts toward.  

What’s the team like?  

The project management department is a wonderful group of colleagues at all different levels of our careers. While we don’t work together within our project teams, as a department we rely on each other for support, meet frequently as a group, and create an environment to share best practices and structure for continual improvement. The project teams I work with are simply outstanding. I could not ask for a better group of extremely smart, scientifically-sound, motivated, and accountable team members to work with. We all share similar passions for bringing molecules to cures. Fast.

What advice would you give to someone applying for a role in your team?  

Do you like being an integral part of developing treatments and cures for patients? Does the word communication spur thoughts of opportunity and teamwork? Is customer satisfaction just as rewarding to you as it is for them? If yes to these questions, you would thrive in the project management team at Quotient Sciences.

What do you like most about working at Quotient Sciences?  

As a project manager, you start to build your team camaraderie and effectiveness by ensuring all members understand the project's purpose, objectives, and expectations. We have a great teamwork environment where we all hold each other accountable through support and motivation.  

The business lives by its manifesto, which is another aspect I like about working at Quotient Sciences. Decision-making is built around this, our culture fosters this, and our efforts in innovations are piloted by this. It is a rewarding feeling after every day knowing that what was accomplished daily was achieved through a business structured in integration and adaptiveness, enabling our projects to run better and ultimately achieving our manifesto in the process. 

Summary: Dr. Vanessa Zann explains how Translational Pharmaceutics® supports drug product optimization by integrating formulation development, real-time manufacturing, and clinical testing. She highlights how this adaptive approach accelerates decision-making, reduces risk, and improves efficiency across development stages.  

It is well known that traditional drug product optimization processes take significant time.

Great emphasis is placed on laboratory and preclinical assessments to identify human formulations. Even though data do not adequately capture the performance of the dosage form in vivo, and the translation from the preclinical species to humans is suboptimal, drug developers often invest a significant amount of time and resources at this stage.

There is a critical need to rapidly enter clinical testing of new chemical entities (NCEs) in humans, assess their performance, and optimize as needed.

What is Translational Pharmaceutics®?

Translational Pharmaceutics® is an integrated approach to drug development. It is an innovative platform proven to shorten development timelines by 12 months or more. First applied in 2008, the platform uses clinical data to improve decision-making and halve development timelines.

How is Translational Pharmaceutics® used?

Quotient Sciences Translational Pharmaceutics® is a powerful solution to address the challenges of drug product optimization, in particular, which is one main application. 

In a recent client example, we supported the development of an extended-release drug product for overdose protection of a prescription drug. This was a complex program using a prodrug that requires activation by trypsin in the gastrointestinal tract and an inhibitor that requires delivery over an extended duration due to its short duration of action. 

We were able to help the customer adjust the release rate and dose for the immediate and extended-release beads across a two-part clinical study to support our client in meeting their goals. This was done using the concept of a "design space" to test ranges of doses and other critical to performance parameters in a clinical program. 

Applying Translational Pharmaceutics® to drug product optimization

Translational Pharmaceutics® has been successfully applied to over 300 drug product optimization programs, delivering significant benefits in areas including solubility enhancement activities. Learn more about how we apply pharmaceutical design spaces to ensure more streamlined development.

Summary: Thierry Van Nieuwenhove joined as CEO of Quotient Sciences in 2023. Thierry discusses the company's unique approach to accelerating drug development through Translational Pharmaceutics® platform, a platform that integrates CRO and CDMO services that are traditionally provided by siloed vendors, thereby streamlining the drug development process. He highlights Quotient Sciences' commitment to delivering innovative drug development programs and the dedication of its colleagues across the UK, US, and Europe in supporting clients' success. 

Quotient Sciences' growth as a CRDMO and role in accelerating drug development

In this interview with Thierry Van Nieuwenhove, Quotient Sciences' Chief Executive Officer, we talk about the unique factors that set the company apart, the strategic growth plans aimed at enhancing the delivery of innovative drug development programs, and how the dedication of our colleagues across the United Kingdom, United States, and Europe is instrumental in helping our customers accelerate drug development every day.

Since joining Quotient Sciences in October 2023, what have been your impressions of the company so far? 

Thierry Van Nieuwenhove (TVN): It was humbling to see the impact that Quotient Sciences’ Translational Pharmaceutics® platform has delivered for our customers such as Ensysce Biosciences , DayOne Therapeutics, Oxilio, and many others over the past 16 years. The relationships that we have built, both with small biotechs and with large Fortune 100 pharmaceutical companies, have been impressive to see.

Each program we’ve supported has come with its own development story, but all ultimately resulted in expedited delivery of medicines to patients—an important goal that we always keep in mind and share with clients. 

There is not a CDMO or CRO out there today that offers a platform quite like Translational Pharmaceutics®, let alone one proven to remove a year or more from conventional drug development timelines in the way that Translational Pharmaceutics® can when it comes to integrating drug substance, drug product, and clinical testing activities. 

We’ve supported over 500 drug development programs via Translational Pharmaceutics® for a broad range of clients, including many repeat customers. I am proud to be part of a company that is not only delivering drug development in a unique way for our customers but with a track record of impactful time and cost savings that ultimately helps increase the success rate of new medicine approvals. 

Did anything surprise you about the company? 

TVN: Quotient Sciences is known for its reputation of providing deep technical and scientific consultation in the design and manufacture of small-molecule drug products, with proven formulation development expertise. As a company, though, we offer even more than some may realize to make us a more holistic CDMO/CRO outsourcing partner with integrated capabilities.

Capabilities and expertise for drug substance API synthesis and manufacturing from our Alnwick, UK facility, and complimentary services through our partnership with Charles River Laboratories provide early opportunities to partner with customers coming out of candidate and preclinical development. Additionally, we are expanding our preclinical development services this year with new capabilities being added at Nottingham.

From our Miami, FL, and Nottingham, UK facilities, we offer clinical pharmacology services, including the ability to conduct Phase I clinical programs with healthy volunteers and support services for data science and analytics. Downstream, we can scale up drug products for later-stage trials, although we don’t have a hand in conducting those trials directly with patients, and can commercially supply drug products for marketed products.

Ultimately, no matter how a customer chooses to work with us and where they work with us, I want our customers to know that the dedication and expertise of our more than 1,300 colleagues will help deliver success.

How does Translational Pharmaceutics® add value in drug development?

TVN: Translational Pharmaceutics® integrates formulation development, on-demand and adaptive GMP manufacturing, healthy volunteer clinical testing and data analysis within a single organization. A unified project management team helps coordinate all activities.

In that sense, Translational Pharmaceutics® transforms the traditional outsourcing model, where a combination of CDMOs and CROs are usually required with handovers at different points throughout a drug program. In doing so, the platform offers significant success rates linked with time and cost efficiencies. 

Translational Pharmaceutics® helps clients access information faster so they can make more informed decisions based on emerging human clinal data, gives flexibility to optimize formulation compositions within a study, and reduces drug substance consumption by up to 85%.

A recent application of Translational Pharmaceutics® was our collaboration with YourChoice Therapeutics, a pioneer of hormone-free family planning products. 

Having established a scale-up-ready synthetic route for the YCT-529 API at our Alnwick, UK facility, our team developed the initial product formulation and the first-in-human (FIH) clinical protocol in parallel. Once approved, this allowed our Nottingham, UK facility to perform on-demand drug product manufacturing for precision dose escalation, removing extensive and costly upfront product manufacturing. 

The YourChoice team also complemented our relationships with UK regulatory bodies, which helped navigate and overcome regulatory hurdles to bring YCT-529 to clinical testing sooner. 

Looking ahead, what are some of Quotient Sciences' top priorities?

TVN: Although 2023 was a difficult year for the entire industry, CDMOs such as Quotient Sciences continued to thrive by providing innovative solutions, a deep understanding of science, and strategic partnership to clients. In 2024, we’re seeing signs of recovery, with some increased biotech industry funding again to support the growing number of new molecules in the development pipelines. 

The expansion of our Translational Pharmaceutics® platform in the US remains one key objective. Many of our customers are based in the United States where we currently have three manufacturing facilities that complement our facilities in the United Kingdom. 

Our Garnet Valley, PA facility develops simple and complex small molecule oral drug products supporting programs from the preclinical stage to clinical proof-of-concept. A nearby facility in Boothwyn, PA offers scale-up to late-phase manufacturing and commercial drug product supply. From there, our clinical pharmacology facility in Miami, FL allows us to conduct first-in-human Phase I clinical trials on-site with healthy volunteers and features a compounding pharmacy. 

Applying Translational Pharmaceutics® under US regulations complements capabilities already offered from our Nottingham, UK facility, so US-based clients have flexibility in where they choose to work to realize the time- and cost-saving benefits that Translational Pharmaceutics® delivers.

Ultimately, no matter how a customer chooses to work with us and where they work with us, I want our customers to know that the dedication and expertise of our more than 1,100 colleagues will help deliver success.

Pharmaceutical R&D continues to grow significantly year-on-year with increasing numbers of pharma companies and therapeutic molecules in development. 

According to the Pharmaprojects Pharma R&D Annual Review 2018, this expansion has been concentrated in Phases I and II more so than in late-phase development with over 2,000 new therapeutic molecules entering clinical research in 2018. 

To address this growing need, Translational Pharmaceutics® helps accelerate timelines and reduce costs in drug development. This innovative approach helps drug developers reach milestones quickly and efficiently for first-in-human studies, drug product optimization, and integrated ADME programs.

Limitations of traditional outsourcing models

Despite increases in spending, the industry struggles with poor R&D productivity. Outsourcing has become more siloed, with separate vendors focusing solely on discovery chemistry, discovery biology, preclinical toxicology and safety, clinical testing, or formulation development and manufacturing.

In the conventional outsourcing approach, the developer engages with multiple vendors, creating both a management burden and gaps in the development timeline. The contract development & manufacturing organization (CDMO) and the contract research organization (CRO) operate in separate worlds, with limited shared knowledge and no operational synergy between vendors, making it difficult for the pharma company to build efficiencies into the drug development process.

Applying an innovative approach to drug development 

The early stages of drug development have been proven to be amenable to an integrated platform that ties together formulation development, real-time adaptive manufacturing, and clinical testing.

Integration of the “make” and “test” supply chains allows drug products to be manufactured to GMP within days of dosing, rather than weeks or months when using conventional processes. By using 14-day “make-test” cycles, a drug product is manufactured and dosed, clinical data are generated (for example safety, pharmacokinetic, pharmacodynamic, or biomarker), and then a decision is made on how to modify the drug product, formulation composition or dosage strength for the next study period.

Our CDMO and CRO integration helps drug developers:

• reach proof-of-concept (PoC) milestones as quickly and efficiently as possible
• accelerate the development of optimized and scalable drug products

How pharmaceutical companies can apply Translational Pharmaceutics®

Implementing a Translational Pharmaceutics® approach can trim six months or more from a typical drug development timeline. As well as immediate cost savings in early development, for a drug product forecasted to generate $500 million to $1 billion in annual revenue, such efficiencies can increase future revenue potential by millions of dollars per day.

In addition, given Translational Pharmaceutics® enables development decisions to be made based on clinical data rather than surrogate in vitro or preclinical data, the program maximizes the potential for success, avoiding the time and cost of potentially repeating multiple rounds of development cycles.

Large CDMOs typically insist on larger than required minimum batch sizes for drug product manufacturing; however, a flexible and adaptive manufacturing approach, tailored to the clinical trial, can reduce API consumption by >85%. That is a significant advantage in early development where API is produced at a small scale and must be carefully rationed to cover numerous activities.

Outsourcing these functions to a single partner that offers integrated capabilities as a single program of work, managed by a dedicated project manager, can significantly ease a sponsor’s management burden and contracting responsibilities. 

Read case studies providing examples of how Translational Pharmaceutics® integrated programs have helped both small biotechs and large pharma clients alike overcome development challenges.

As a new molecule progresses through drug development, the way it is formulated as the drug product or dosage form will change for it to successfully achieve key clinical milestones. 

In early development, the first-in-human (FIH) clinical trial is often a single-center study and typically involves dosing a small number of healthy subjects over a short duration of days or weeks. In this study, the drug is administered in increasing doses and as such, a “fit-for-phase” drug product with high dose flexibility is often used, such as a simple solution, suspension, or powder-in-capsule. 

This type of drug product can usually be prepared on-site, at a small scale, and with limited stability studies and analytical release testing. Simple pharmacy preparations may be sufficient for FIH clinical studies, but when moving beyond Phase I into later stages of clinical development, these products are unsuitable for both patient convenience and scalability to meet larger batch size requirements for Phase II trials.

Scaling drug product for Phase II-III clinical trials

Subsequent Phase II-III clinical trials involve a larger number of patients and often take place at multiple clinical sites, across states and countries, over a longer period. To support these trials, the development team will need to bridge to an optimized drug product, such as a solid oral dosage form like a tablet, to ensure patient compliance and suitability for shipping globally. 

Product batch sizes manufactured to support Phase II and Phase III trials need to increase. Later, if the molecule is successful in late phase clinical studies, drug product batches can be scaled to commercial supply.  

Requirements for different drug product formats at each stage of development can result in delays and budget overruns, if not managed well. CMC delays can be prevented by careful planning, earlier technology considerations in the formulation design process, and considering integrated CRDMO drug development activities to remove time and cost of managing multiple CRO and CDMO providers.

Bringing new molecules to market as quickly as possible

To improve R&D productivity and bring new molecules to market as quickly as possible, drug companies are actively seeking new ways of streamlining drug development using alternative outsourcing models. Using the Translational Pharmaceutics®  platform, a novel approach for integrated drug development, Quotient Sciences coordinate drug product manufacturing requirements with a clinical development plan, making and testing formulations in a streamlined way to gain time and cost efficiencies.

Druggability Technologies (DRGT; now part of Tavanta Therapeutics) was a specialty pharmaceutical company dedicated to the development and commercialization of high-value proprietary drugs to deliver measurable improvement in clinical utility. Translational Pharmaceutics® was used to advance the development of DRGT-46, a fast-acting formulation of celecoxib. 

Earlier access to clinical data helped DRGT drive formulation selection in real-time, allowing the company to efficiently bridge from a Phase I drug product, up to a dosage form suitable for patients as they were entering late-stage clinical trials.

Continue reading to learn more about how Translational Pharmaceutics® was applied to DRGT-46, or contact us today if you have any questions about how our integrated CRDMO solutions can help advance your next drug program.

Summary: Dr. Vanessa Zann explores strategies for modified-release formulation development, highlighting technologies such as controlled-release, multiparticulate systems, and osmotic delivery. She explains how Translational Pharmaceutics® integrates formulation design with real-time clinical PK data to overcome prediction challenges and reduce development risk. This adaptive approach ensures optimized drug performance and efficient progression from early development to commercialization.

Modified release dosage forms are increasingly used to enhance oral drug product performance. 

For decades, modified-release drug products formed part of a line-extension category and were launched in a strategic way to offer a better product relative to commercial immediate-release products, thereby extending the life of the brand. 

Today, pharma and biotech companies are increasingly considering modified-release technologies earlier in the development process of a new chemical entity (NCE) to obtain greater differentiation against other products in development or on the market. All stakeholders including investors, patients, doctors, and payors welcome this trend, especially where clearer therapeutic benefits are shown.

What benefits do modified-release formulations offer?

Many drug product improvements can be achieved using modified-release technology. Some examples include:

• Improved patient compliance: modified-release technology can allow for simpler, once- or twice-daily dosing
• Enhanced pharmacokinetic (PK) profile: modified-release dosage forms can be suited to the therapeutic window or to the patient’s needs, such as adjusting drug blood levels between daytime and nighttime
• Reduced side effects: a modified PK profile can lower the Cmax of the drug or its metabolites while still maintaining therapeutic plasma levels

The benefits of modified-release products are significant but can come with technical challenges that prevent or complicate their development. When evaluating a modified-release product opportunity, we often start with two fundamental questions:

• What is an appropriate modified-release technology to achieve the therapeutic goal of the drug?
• What is the right development plan to efficiently demonstrate proof-of-concept for the modified-release product?

Modified-release formulation approaches range in complexity, and the formulation selection needs to be based on the properties of the drug substance and the target drug release profile. R&D programs can encounter large delays and cost overruns when the wrong modified-release technology and development plan are selected.

Our experience in the development of modified-release products spans numerous modified-release technology platforms: controlled release, gastro-retentive, delayed release, pulsatile, and biphasic release.

What is an appropriate modified-release technology to achieve the therapeutic goal of the drug?

A variety of modified-release formulation technologies are available to be manufactured using common tableting, encapsulation, and coating processes (either pan or fluid bed coating). The specific modified-release behavior is also determined by the functional excipients used. 

A common approach is to use hydrophilic polymers in a tablet that form a gel matrix in in-vivo that controls drug release out of the matrix. Polymer coatings are also applied either on tablets or multi-particulates, for example using beads, with functionality that may be pH-dependent. An erodible coat, or a coat that controls drug diffusion through a semi-permeable coat or orifice, may also be used. Both the excipients and the final products used are generally non-proprietary. 

Among the more complex modified-release technologies are osmotic tablets, using the approaches described and sometimes also including a small orifice that contributed to release-rate control, and gastro-retentive formulations that apply a range of swelling, floating, or adhesion methods to delay gastric-emptying of the dosage form.

What is the right development plan to efficiently demonstrate proof-of-concept for the modified-release product?

A traditional approach to screen and selecting formulation prototypes begins with in vitro testing and animal models, and then a lead prototype or prototypes are selected for clinical testing. This approach and overconfidence in non-clinical to clinical predictions can be flawed when developing oral modified-release formulations because the behavior of the modified-release formulation is highly dependent on human physiology and this dependence occurs over a longer duration of drug release.

Across modified-release drug programs, we often see that clinical performance of modified-release products differ considerably from in vitro or animal test predictions. This often provides a surprise for the drug development team but confirms why non-clinical tests should not be the backbone of a modified-release product development program. 

Using Translational Pharmaceutics® allows us to make formulation adjustments in response to human PK data during the clinical study to accelerate development timelines. Using a science-driven approach, we are able to help clients derisk drug development. For more insight about this topic, watch our webinar on-demand: Non-Clinical vs Clinical: Risks & Considerations When Developing Modified Release Dosage Forms.

As a company that prides itself on science and innovation, Quotient Sciences has continued to work collaboratively with our customers over the last 12 months to publish research findings from programs of work that we perform. 

In 2019, Quotient presented 11 podium talks and 13 scientific posters at international conferences, and was involved in four peer-reviewed articles published in scientific journals.

We are grateful to our customers who have been willing to have their work published and to all of the scientists involved in the design and delivery of these projects. Sharing the information with the wider pharmaceutical development community will help with our collective goal of accelerating the delivery of new medicines to patients around the world.

Details and links to some of the top papers and posters are below. If there is something of particular interest and you would like further information then please get in touch.

Assessing the Financial Impact of Translational Pharmaceutics®

“Tufts Center for the Study of Drug Development (CSDD) white paper sharing study results that indicate Quotient Sciences’ Translational Pharmaceutics® platform reduces development times by >12 months and lowers R&D costs by >$100 million per approved new drug, compared to traditional multi-vendor development paradigms.” 
Access here

Peer-reviewed article in collaboration with Genentech:

Absence of  Pharmacokinetic interactions between Bruton's Tyrosine Kinase Inhibitor Fenebrutinib and Methotrexate
Access here

Peer-reviewed article in collaboration with Mitsubishi:

Absorption, disposition, and metabolic pathway of amiselimod (MT-1303) in healthy volunteers in a mass balance study
Access here 

Peer-reviewed articles in collaboration with DRGT:

Dose Escalation Study to Assess the Pharmacokinetic Parameters of a Nano-amorphous Oral Sirolimus Formulation in Healthy Volunteers
Access here
 
A phase 1/1b study of PUR1900, an inhaled formulation of itraconazole, in healthy volunteers and asthmatics to study safety, tolerability, and pharmacokinetics
Access here

Poster presented at the European Paediatric Formulation Initiative (EuPFI) conference:  

"Development of Oral Liquid Products for Neonatal Patients"
Access here

"Development of a Paediatric Oral Suspension of a Novel Drug for the Treatment of Kidney Disease"
Access here

Poster presented at the AAPS Pharm Sci 360 conference:  

"Applications and Benefits of Healthy Volunteer Trials to Accelerate Oncology Drug Development"
Access here

"Comparison of Two In-Silico Modeling Programs, ADMET Predictor®, and Percepta® to Predict Intrinsic Solubility and pKa of Poorly Soluble Drugs"
Access here

"A Phase I Study Allowing Clinical Screening of Multiple Solubility-Enhancement Formulation Technologies, and an Assessment of Food, PPI and Dose Linearity Assessment with the Selected Formulation of BOS172767, in Healthy Volunteers"
Access here

"Development of a Solubilised Capsule Formulation Using Co-Micronisation and Precipitation Inhibition"
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"Rapid Transition of a Novel Celecoxib Formulation from a Fit-for-Phase Presentation to a Commercializable Product Using an Innovative Integrated Drug Development and Clinical Testing Platform"
Access here

Poster presented at the American Heart Association (AHA) conference:

Huya Biosciences International - "HBI-3000: A Novel Drug for Conversion of Atrial Fibrillation - Phase 1 Study Results"
Access here
 

In Part 1 of our two-part blog piece on the 'The challenges and opportunities of Pediatric Dosage Form Development', Nazim Kanji, Executive Director of Pediatric Services at Quotient Sciences, covered key considerations in pediatric program design and formulation development strategies that sponsors should take into account if they want to successfully bridge from initial concept into later stages of development and through to commercialization.

Adult taste/PK study

After formulation development, the next stage is typically a clinical assessment of the proposed pediatric formulations in adult volunteer panels to evaluate and optimize the taste and/or PK attributes, before dosing the formulations in pivotal pediatric patient studies.

Over the last decade, Quotient Sciences has developed a novel platform called Translational Pharmaceutics® that integrates GMP manufacturing and clinical testing. Drug products are made and dosed quickly in a matter of days, with flexible CMC submissions and adaptive clinical protocols allowing formulation compositions to be optimized based on emerging clinical data. 

Translational Pharmaceutics is therefore an extremely efficient means of characterizing and optimizing the clinical performance of new prototype formulations.

This platform has been successfully applied to the assessment of pediatric formulations.

For example, in the selection of flavor/sweetener systems to overcome aversive drug properties, and to understand the PK performance of new age-appropriate medicines and thereby inform dose selection in the pediatric population.

Clinical supplies for pediatric patient trials

Once the pediatric formulation has been optimized, the drug product will then be taken into patient studies to assess efficacy in the target disease population. This can present the development team with new challenges, putting a strain on traditional product manufacturing and supply logistics, particularly if dealing with rare and orphan disease states. 

Typical challenges include:

• Sporadic, challenging, and slow patient recruitment
• Multiple sites and countries to recruit the required number of subjects
• Patient weight variability requiring dose flexibility (mg/kg or body surface area)
• Formulation stability may be limited
• Small batch size requirements

The historical practice of large product batch sizes with relatively long shelf lives and long cycle times to get products manufactured, released, labeled, packaged, and shipped is therefore unlikely to fit the supply requirements of typical pediatric clinical studies. Implicit in this is also a lack of ability to customize the drug product around unique, individual patient needs.

Challenges can be successfully addressed by using a real-time manufacturing and supply model that enables drug products to be tuned to individual patient needs and the design of the clinical trial.

Customized products can be manufactured, released, and shipped for global patient studies within 1-3 weeks of subject eligibility and formulation requirements being confirmed, to get the right product to the right patient at the right time.

Commercial manufacture of pediatric products

Finally, there will be a need to identify a long-term commercial partner with the capability to manufacture liquid or solid dosage forms and supply to global markets, for what may be relatively low-volume commercial products. 

Given that in-house Large Pharma and the CMO service sector have traditionally focused on high-volume and low-variation drug products, there is an emerging industry need for smaller-scale, batch manufacturing.

The development of pediatric medicines is an industry requirement to ensure safe and efficacious treatments are available for children of all age groups.

Many factors need to be considered for the successful development of pediatric products for which Quotient Sciences has unique expertise and provides an end-to-end integrated solution across the design, development, and supply continuum.

 For more information, visit pediatrics capabilities, or contact us.