Summary: Dr. Aruna Railkar, Senior Drug Development Consultant, 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. It 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. 

Video: 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 and modified release drug development activities. 

In this video, watch Aruna Railkar, Senior Drug Development Consultant, speak on this topic at the 2024 Controlled & Modified Drug Release Summit in New Jersey about how we apply Translational Pharmaceutics® to drug product optimization.

Want to discuss your next program and how we might be able to help? Contact us today.

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 batch sizes for Phase II and Phase III trials

Subsequent Phase II and Phase III patient trials involve a larger number of patients and often take place at multiple clinical sites, across states and countries, and 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 will need to increase to support the increased number of patients. If the molecule is successful in clinical studies, batch sizes will be scaled up to meet the demand for a commercially approved product.

Requirements for different product formats at each stage of development can result in delays and budget overruns when it comes to product optimization and scaling up. Sometimes, CMC delays can be prevented by careful planning, and integrating development activities and technology considerations in the formulation design process. 

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. At Quotient Sciences, we coordinate drug product manufacturing requirements with a clinical development plan, to make and test formulations in a streamlined fashion. This leads to significant time efficiencies and cost savings. 

Druggability Technologies (DRGT; now 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. They used the Quotient Sciences Translational Pharmaceutics® platform to advance the development of DRGT-46, a fast-acting formulation of celecoxib. 

Clinical data was able to help DRGT drive formulation selection in real-time, allowing the company to efficiently bridge from a Phase I drug product to a dosage form suitable for patients in late-stage clinical trials. Continue reading the DRGT-46 case study to learn more about how Translational Pharmaceutics® was applied. 

When you are looking for a partner who can help develop your drug product from first-in-human through to proof-of-concept and beyond, rely on Quotient Sciences. Contact us today to get started with your 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.

Participant recruitment is one of the biggest bottlenecks in clinical research today. 

In early drug development, effective volunteer recruitment is critical for building a robust package of clinic trial data, ensuring scientific validity, containing study costs, and maintaining timelines. In studies that require specific types of volunteer populations, it’s important to develop a focused plan for recruitment.           

Different populations may demonstrate widely varying responses to drug therapies due to physiological, lifestyle, or other disparities. To safeguard those for whom standard requirements may not offer sufficient protection, special populations provide an evaluation of factors such as dosage or dose interval modifications to address these differences.

For example, individuals over the age of 65 are more likely than younger individuals to take multiple drugs concurrently, making drug interactions of particular concern. Because older populations respond differently than younger patients to drug therapy, obtaining clinical efficacy and safety data for these populations is critical in early drug development.

Furthermore, growth in global pharmaceutical markets is driving drug development in Europe and Asia. Multi-ethnic approaches to clinical trial programs, such as ethnobridging for native Asian populations living in other countries, must account for cultural differences to satisfy international regulatory authorities.

If you’re a sponsor, it will be of utmost importance to work with a trusted contract research organization (CRO) that is transparent about timelines and can guide your expectations. 

An experienced partner can effectively target hard-to-recruit populations such as the elderly, post-menopausal, hypertensive, and healthy smokers, to name a few.

An organization that has completed multiple studies with similar types of populations will have a baseline understanding of recruitment challenges and can provide an honest assessment of the time expected to recruit the full cohort. When studies have stricter criteria or more screening procedures for qualification, recruitment will require more time. It’s important to find a partner that provides a realistic, trust-based approach to recruitment rather than one that promises to quickly recruit every participant.

In addition to identifying appropriate study participants, the right partner can help minimize screen failures due to multiple exclusion/inclusion criteria. 

Such a partner will demonstrate a successful track record with metrics including:

• Number of studies completed
• Database size and number of active healthy volunteers
• Recruitment timelines and strategies for special subject populations
• Communicate effectively

Sponsors may consider the following five tips when it comes to interviewing and partnering with a CRO for their early drug development needs.

Inquire about the volunteer database

When rapid study startup is critical, a robust database provides an immediate starting point for recruitment. A large database demonstrates that the CRO has access to an adequate population of volunteers who understand clinical research and are amenable to participating. Consistent recruitment activities and a database of multiple trials also can help keep volunteers active.

Consider your CRO's location

Whether your trial must be conducted at a single site or multiple sites, you may want to consider the location of the sites available and their advantages and disadvantages. Facilities in larger cities tend to recruit from more ethnically diverse populations or those with better access to public transportation options. The longer the facility has been in existence, the more established relationships it will have with the local community and population.

Know what questions to ask your CRO's

To determine how the CRO will prioritize your study, ask whether it is recruiting for multiple studies of the same kind concurrently. If so, your study would compete with others for the same volunteers and consequently have access to a smaller pool of potential participants, which could delay your recruitment completion. Ask about recruitment and screening timelines, because extended timelines could indicate difficulty recruiting that population. Determine if full trial cohorts can be enrolled at one time or if there is a need to divide them into sub-cohorts for admission, which could be another indicator that the site has difficulty enrolling a specific population.

Employ best practices regarding patient safety

If you have concerns about volunteers participating in overlapping studies, work with a partner who uses a registry that tracks volunteers and their participation in trials, including the date of the last dose of a study drug. This information will help establish a sufficient wash-out period, during which the participant receives no active medication. Such registries are confidential and established through fingerprinting, and they enhance patient safety as well as facilitate data integrity.

Find a CRO that can integrate services

Look beyond the CRO’s ability to recruit large cohorts of volunteers and examine its track record of complete study delivery, including the expertise of its team of medical directors and project managers, as well as other capabilities. The right partner can also guide protocol development and study design to maximize your clinical data output, and rapidly deliver data and insights quickly to move you to the next milestone.

When you are looking for a partner who is dedicated to Phase I trials and early development, choose Quotient Sciences. 

To find out more about our clinical pharmacology capabilities, get in touch with us today.

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.

In this interview, we speak with Clare Preskey about her day-to-day in the Nottingham clinic. 

Clare Preskey is Executive Director of Clinical Operations, responsible for the oversight of day-to-day activities that take place in our Nottingham Phase I clinic. This includes volunteer screening and management, oversight of our clinical laboratory and pharmacy teams to ensure on-time project delivery, and driving continuous improvement and innovation initiatives.

Looking back to when you were first starting your career, was your goal to be where you are now?

I have always held a passion for science and the study of physiology and pharmacology. I started my career at Quotient Sciences in 2010 fresh out of university as a Clinical Scientist. My key responsibilities were ensuring the well-being of our volunteers and the collection of clinical data.

Later, I moved into Project Management, where I gained valuable experience in customer management and developed a broader understanding of our business. I held several roles within Project Management, last as a Team Lead prior to moving into a clinical operations role. I have always held a passion for clinical sciences and operational excellence, so my current role is a great fit. 

What are some of the biggest changes and improvements that you have seen over the years at Quotient Sciences?

When I first joined the company, we were a much smaller business: one building containing a 30-bed clinical unit, a GMP suite, and approximately 100 employees. The people at Quotient Sciences are at the heart of the business; we have a great culture and tight-knit teams. Close teamwork is imperative when managing complex and integrated projects in short timeframes for our customers. 

Quotient Sciences has always had a focus on continuous improvement and high-quality standards. The biggest change has been the expansion in facilities and capacity, including the evolution of our Translational Pharmaceutics platform, over the last 10 years. Despite our growth, the ethos of who we are and what we do has not changed. We’ve been able to retain our core values, agility, and integrated processes.

We never stand still; we are always pushing boundaries, trying to do things better and more efficiently! I am privileged to work with such committed, talented teams. 

How do the different functions work together to deliver Translational Pharmaceutics programs?

Teamwork is key to any Translational Pharmaceutics program and establishing cohesive communication channels across departments. Our processes have been built over many years, with SOPs and protocols geared to be adaptive. Planning is also an essential practice that is embedded in our operational processes (e.g. kick-off meetings) to ensure the highest quality project delivery that is the right first time.

What do you enjoy most about your role and why?  How do you see your role evolving as the business grows?

The environment at Quotient Sciences is dynamic and fast-paced. Every day brings different challenges and opportunities! 

We work with so many different customers, molecules, and study designs. My colleagues are incredibly passionate and dedicated to every one of our projects and customers. We learn and grow together, expanding our knowledge and gaining new skills. Getting things right the first time is very important to me.

I love what we do and I always feel energized to come to work, ready to learn and take on the next challenge. 

Summary: Oncology drug development continues to be a major focus in the pharmaceutical industry, with over 5,500 molecules in development—representing more than 35% of the global pipeline. Despite the high unmet medical need, oncology programs face low success rates and extended clinical timelines due to complex trial designs and patient recruitment hurdles. In this Q&A, John McDermott, VP of Scientific Consulting at Quotient Sciences, discusses the challenges and trends shaping the oncology landscape. 

Oncology development trends and drug product manufacturing

A: Oncology drugs dominate today’s research focus with over >5500 molecules in development, representing over 35% of the total industry pipeline. In 2019, 10 new oncology drugs were approved by FDA, of which half had an orphan indication and all had been granted priority review.

With over 300 oncology projects completed in our drug development history, Quotient Sciences offers end-to-end support to bring oncology therapeutics from drug product formulation development through to commercial manufacturing. Our high-potency API (HPAPI) capabilities, flexible batch sizes, and global regulatory approvals make it us trusted partner for oncology drug developers.

In this Q&A, John McDermott, VP of Scientific Consulting at Quotient Sciences, discusses the challenges and trends shaping the oncology landscape. 

Q: What are some of the trends and challenges in the development of oncology therapeutics?

A: Given the number of molecules in development, there is so much pressure on development teams to identify successful drug candidates as quickly as possible, and accelerate patient access, particularly where no effective therapies are currently available. 

However, the oncology therapeutic area remains a challenging one to navigate and success rates are low. The likelihood that a molecule entering Phase I trials will reach market is around 10%, with the average duration of an oncology clinical trial taking 40% more time than other therapy areas due to the difficulty in patient recruitment.

Oncology drug development has seen a significant shift in focus as molecule chemistries and drug technologies have improved. Historically, most oncology drugs were cytotoxic compounds with poor safety profiles. In recent years, a better understanding of cancer aetiology has improved drug target specificity of oncology compounds, leading to the advent of molecular target agents (MTA), with more favorable safety profiles. 

Targeted small molecules currently make up around 40% of the global oncology pipeline, whereas cytotoxins have fallen to just 7%. This movement has opened the opportunity to use more convenient dosage forms, with oral administration considered the gold standard for patient compliance. 

Understandably, compared to the intravenous dosage forms, the move to oral solid dosage forms brings a different set of biopharmaceutics challenges that need to be overcome.

Q: What types of development and manufacturing services does Quotient Sciences provide for oncology therapeutics?

A: We've worked on more than 300 projects and over 91 different oncology drug candidates across different indications. As a fully integrated drug development, clinical testing and manufacturing organization, we're well positioned to address the challenges associated with developing small molecule oncology therapeutics. 

Our extensive formulation development capabilities and flexible approach to clinical drug product manufacturing, with capabilities to also manufacture drug product up to commercial scale, makes us a valued partner for anyone looking to advance oncology therapies.

Additionally, for almost two decades, the Translational Pharmaceutics® platform has been able to remove extra time and steps from oncology drug development. Consolidating drug product and clinical testing within a single program of work helps reduce the burden of outsourcing, while providing a resource-efficient approach to clinical trials. 

We've demonstrated that formulation flexibility in Phase I healthy volunteer trials can be used to develop “patient ready” formulations for oncology molecules in less than half the time of the industry standard through applying the Translational Pharmaceutics® platform. Another benefit is the ability to modify dosage forms for additional areas of need, such as pediatric patients.

Q: Are there any other specialized drug product manufacturing services that Quotient Sciences provides for oncology therapeutics?

A: Global demand and growth for targeted oncology therapeutics has led to an increase in the manufacturing of high potent active pharmaceutical ingredients (HPAPIs). This has driven the need for high potency handling capabilities, particularly high-containment manufacturing facilities. 

Handling these ingredients in the drug supply chain requires specialized equipment and enclosure systems in order to avoid cross contamination, product protection and to ensure operator and environmental safety. Our facilities have the necessary handling and containment capabilities, and our teams are trained as well on safe handling procedures to minimize EHS risk.

We use the PBLEC system to classify HPAPIs at Quotient Sciences. We look at the type of compound, dosage form, manufacturing process, and batch size required. Our cGMP manufacturing suites are outfitted with the necessary engineering controls to handle PBLEC system 1-5 rated compounds. 

Our facilities have been inspected and approved by all major regulatory bodies, including the FDA and MHRA. From design of experiments (DoE), to registration batches and process validation, our formulation and manufacturing scientists have the experience needed in order to ensure a scalable drug product and successful commercial launch.

For most compounds, the route from preclinical to clinical is clear. In oncology drug development, the path is different. 

Traditionally, early-stage cancer drug trials involve patients due to potential safety concerns. However, newer targeted treatments with better safety profiles can be tested on healthy volunteers. Conducting Phase I trials in healthy volunteers can speed up development and reduce costs, while still providing valuable safety and effectiveness data. This article discusses how healthy volunteer studies offers benefits like consistent results, easier recruitment, and simpler study logistics.                

For many new molecules, a comprehensive safety preclinical toxicology package is generated and the data from that package is used to design the first-in-human (FIH) study in a healthy volunteer panel. This Phase I study will test the safety and tolerability of the compound, as well as its pharmacokinetics in single, and multiple ascending doses. The data study from the Phase I study provides the springboard for the rest of the drug development program.

In oncology drug development, however, the path can be somewhat different. 

Traditionally, drugs that have oncology indications have poor safety and tolerability profiles, to the point that dosing them in healthy volunteers presents too much risk, and could be considered unethical. This coupled with the vast unmet patient need for effective oncology treatments means that the FIH study changes from dosing healthy volunteers to dosing directly in patients.

The benefits from this strategy are plain to see; preliminary efficacy data far earlier than the traditional route, safety and tolerability assessments which are directly relevant to the expected patient group, and giving patients earlier access to new treatments. Regulatory agencies require a reduced preclinical data package for straight-to-patient studies compared to the healthy volunteer route for oncology drugs, saving the drug developer time and cost.

Equally, there are acknowledged challenges with performing Phase I trials of any type in a patient population. Subjects involved in these studies are patients for whom no current efficacious treatment is available. Severe comorbidities, the presence of multiple diseases or medical conditions, can cloud the safety profile of the new test products. The disease state of these subjects also brings with it inherent variability into the drug’s pharmacokinetics, often due to hepatic or renal impairment. This further complicates assessments of safety, tolerability, and efficacy because the exposure of the compound from subject to subject can vary significantly. Furthermore, recruiting and conducting these studies can be logistically challenging, requiring multiple sites and a much longer study duration than a Phase I study in healthy volunteers.

In the last 5 years alone, we've performed over 50 Phase I studies of various types, all with a goal to reduce the time and cost of the development of oncology molecules.

Where safety allows, there can be compelling drivers for using healthy volunteer trials to develop oncology molecules. Recent improvements in drug discovery have led to a new generation of oncology-targeted molecules that are more specific and rely less heavily on general cytotoxicity. New generations of molecules known as molecularly targeted agents (MTA) usually have a favorable safety profile that can make them suitable for dosing in healthy volunteer studies. 

There are significant, tangible benefits for studying oncology molecules in healthy volunteer studies, for example:

• There is less variability within a healthy volunteer population. By their nature, healthy volunteers have more consistent physiology specifically regarding clearance routes, leading to less variable pharmacokinetic data. The absence of co-morbidities makes assessing drug-related adverse events clearer.
• Healthy volunteer studies, typically, have less challenging logistics. Studies in healthy volunteers can be run at any Phase I clinic with experience translating oncology molecules into healthy volunteers. Studies can usually be conducted at a single site, and healthy volunteers are ubiquitous to the general population, leading to simpler, faster recruitment.

In the last 5 years alone, we've performed over 50 Phase I studies of various types, all with a goal to reduce the time and cost of the development of oncology molecules, including:

• First-in-human clinical studies where a molecule has presented significant biopharmaceutic challenges and formulation selection to ensure adequate bioavailability have been uncertain
• Relative bioavailability studies to optimize formulation compositions that were previously dosed only in oncology patients
• A full spectrum of clinical pharmacology studies, including food effect, human ADME, and drug-drug interaction studies

Getting preliminary information on efficacy as early as possible is of significant importance to oncology compounds in order to ensure that any patients taking the compound are not being exposed to ineffective or sub-therapeutic levels of the drug. With a healthy volunteer study, this understandably becomes more difficult, but not impossible. Healthy volunteer studies can still deliver meaningful pharmacodynamic data. 

An understanding of the pharmacology of the drug can allow for the use of clinically relevant biomarkers, for example, in the following paper, inhibition of basophil activation was used as a substitute marker for efficacy for a drug that targeted the PI3K delta pathway, and the data generated from this study helped to inform on the recommended Phase II dose.

While the majority of oncology development is geared towards patient studies, traction is building in the use of healthy volunteers for the Phase I drug development program.

Unlike other indications, translating an oncology molecule into a healthy volunteer study has a unique set of challenges, which is especially true for FIH studies. A medical review of the safety data will be required to assess whether the drug is suitable for healthy volunteer studies, following which a gap analysis of the preclinical safety package needs to identify if the regulatory agencies will require additional studies beyond what would be expected for a direct-to-patient route.

While the majority of oncology development is geared towards patient studies, traction is building in the use of healthy volunteers for the Phase I drug development program. Contact us to find out more about our latest oncology drug development updates.