Drug Development & Delivery spoke with Nazim Kanji, Executive Director, Pediatric Services, about the unique considerations and challenges when developing palatable pediatric formulations, so that molecules can become cures, fast.

Quotient Sciences: Unique Considerations & Challenges When Developing Palatable Pediatric Formulations

Read highlights from the article below. For the full article, visit Drug Development & Delivery.

The demand for pediatric dosage forms continues to increase; however, the number of approved pediatric drug treatments on the market remains substantially less than those for adults. Developing drug products for pediatric patients brings a whole set of unique challenges for development teams. Formulation scientists must consider the route of administration, the safety profile, overall taste and palatability, the child’s age, weight, physiologic condition, and the treatment plan’s requirements. All these key factors must be balanced for developing a pediatric product that garners clinical, regulatory, and commercial success.

Quotient Sciences, a drug development and manufacturing accelerator, has extensive experience in developing palatable pediatric formulations on behalf of pharmaceutical and biotech customers globally and has successfully developed customized pediatric pharmaceutical formulations that have received regulatory approval.

Q: What are the regulatory considerations when developing a pediatric formulation, including US and EU incentives, guidance, and requirements?

A: Historically, drug products used in children were generally only approved for adults. They were rarely tested in pediatric populations, and product labelling did not include directions for safe and effective use in pediatric patients. Furthermore, the correct dose and excipient safety were generally not determined for target age groups, and there was a distinct lack of age-appropriate formulations, which meant that in many cases, manipulation of the adult product would be required to dose children.

Pediatric legislation in the form of The Best Pharmaceuticals for Children Act and Pediatric Research Equity Act in the US and the Paediatric Regulation in the EU came into effect between 2002 and 2007. The aim of these regulations was to increase the number of products that were approved for pediatric use, and they sought to do this by mandating companies to undertake pediatric research and development as well as providing financial incentives for them if they invested in doing this work.

Both the US and EU regulations require the submission of pediatric plans at given points in the adult development – in the EU, a Paediatric Investigation Plan (PIP) is to be submitted no later than the end of human pharmacokinetic (PK) studies in adults, while the US requires a Pediatric Study Plan (PSP) to be submitted within 60 days of the end-of-Phase 2 meeting. These documents give a commitment to the studies that will be conducted and also the timeframe.

Q: What are product considerations when developing patient-centric dosage forms that are acceptable and palatable for pediatric populations?

A: To meet patient needs and regulatory expectations, there are several key steps for consideration in the development of a pediatric dosage form. First is the design stage, to understand the target product profile for the defined population(s) along with associated challenges and risks. Formulation development is then required to identify acceptable, age-appropriate dosage form(s). Depending upon the active pharmaceutical ingredient (API) characteristics and formulation strategy, a key factor here, of course, may be taste masking. 

Next is typically a clinical assessment of the proposed pediatric formulations in adult panels to understand, optimize, and clinically validate dosage forms based on taste and/or PK attributes prior to proceeding into pediatric trials. These efficacy studies often present the development team with unique challenges given bespoke patient requirements that can put a strain on traditional product manufacturing and supply logistics. Finally, there may also be the need to identify a long-term manufacturing partner for what may be low-volume commercial products. 

Clearly, there is plenty to think about on this journey!

Q: How can physiologically based pharmacokinetic (PBPK) modeling and simulation be used for dose extrapolation from adults to children and to predict drug product performance in children?

A: There are unique biopharmaceutics considerations concerning in vivo drug and formulation performance in pediatrics given differences in anatomy and physiology when compared to adults – gastric and intestinal factors around pH, transit, surface area, enzyme expression, and microflora can all influence oral bioavailability of some drugs differently in the pediatric population.

At Quotient Sciences, we use GastroPlus® to build PBPK models. To build a robust model for pediatric dose predictions, there is firstly a need to build a robust PBPK model to represent the adult situation. The PBPK model is built on clinical data from a range of studies, eg, SAD, MAD, DDI, food effect, and where possible, different formulations and dosing regimens along with supporting in vitro data. The model must be validated with clinical data independent to that used to build the model to ensure robustness. PBPK models allow the gastrointestinal environment to be tailored so it more closely represents the pediatric physiology and can be used to predict exposure in children from alternative dose formats and/or formulation attributes.

Other factors, such as varying percentages of body water and body fat (which influence tissue distribution kinetics), differences in protein binding, relative blood flows, and size of organs relative to total body weight, are also considered in the pediatric physiologies used in PBPK modeling.

Q: What are some challenges drug developers should be aware of when dealing with taste masking, taste modification, and alternate dosage forms?

A: A common problem in pediatric drug development is that drug substances can be very bitter or have other aversive taste attributes. A key challenge is understanding how to effectively mask these taste properties to ensure patient compliance, especially if the end drug product is intended for pediatric populations who are not able to swallow conventional dosage forms such as tablets and capsules. This can impact drugs across all therapeutic areas and can be influenced by several factors, including the chemical structure of the drug substance, solubility, and dose. It is important to understand the taste characteristics of a drug substance early in the development of a pediatric dose form to aid the selection of an age-appropriate formulation and associated taste-masking strategy.

For the full article, visit Drug Development & Delivery.

NOTTINGHAM, U.K.; Aug. 25, 2021 – Quotient Sciences, the drug development and manufacturing accelerator, announced a £6.3 million-pound investment in its recently acquired manufacturing facility in Alnwick, U.K. The investment will significantly expand Quotient’s drug substance manufacturing capability and will create 80 new jobs over the next three years.

Quotient acquired the Alnwick facility from Arcinova in February 2021 to expand its service portfolio to include drug substance, drug product and clinical testing capabilities all under one organization. The acquisition enables Quotient to support customers with an “end to end” offering from candidate selection through commercial product launch. The multimillion-pound investment will repurpose a 1,500 square-meter footprint and incorporate additional equipment and technologies — significantly expanding the number of new molecules developed each year.

Additional equipment, featuring the latest advances in digital control and data capture, will ensure robust transfer from laboratory to multi-kilo scale production. Plus, processing equipment with new developments in modular continuous technology will maximize responsiveness and agility for manufacturing processes. These updates, combined with a five-fold increase in scale, will increase Quotient’s capacity by over 10 times for developing complex medicines.

“Following our integration into Quotient Sciences earlier in the year, it is tremendously exciting to see the Alnwick facility continue to expand capabilities as we move into larger scale and commercial manufacturing,” said Quotient Sciences SVP Candidate Development Services Roger Kilburn.  “Science and agility are at the core of Quotient Sciences, and our team strives to innovate and develop smarter approaches to process R&D for our customers and drive the adoption of continuous processing technologies.”

The Alnwick facility employs 170 people across a range of scientific disciplines, and this investment will create a variety of new jobs. Quotient continues to grow and was recently presented an award for “Most Inspirational North East (U.K.) Science Employer,” from STEM Learning, as part of the STEM Ambassadors program.

View this press release here.

Featured Interview with Mark Egerton, CEO of Quotient Sciences with Global Business Reports

How was 2021 for Quotient Sciences, particularly within the US?

In February 2021, Quotient Sciences expanded its portfolio of services to include drug substance and bioanalysis capabilities by acquiring the Alnwick facility from Arcinova, a UK-based CDMO. Over the past year we have been focused on fully integrating these capabilities into our core Translational Pharmaceutics platform, saving our customers significant time and costs by integrating drug development and clinical testing services within a development program under a single clinical protocol. We also went through a series of organic investments at five of our seven sites, where we have been increasing drug substance, clinical trial manufacturing, and clinical testing space. These investments have either been completed or are ongoing and will be completed in 2022. In recent years, there has been phenomenal investment in pharmaceutical R&D, and the number of molecules continues to grow. Aligned with this increase, Quotient Sciences’ customer base has grown to approximately 500 customers across the US and Europe. We have operating sites in both the UK and the US, but 80% of our revenues are generated from US-based customers.

Can you explain the importance for drug developers to have a CDMO that can manage both drug substance and drug product in parallel?

Quotient Sciences wants to support our customers with their molecules earlier in the development process, from the point at which the drug candidate molecule is selected from the discovery program. By incorporating our scientific expertise and development technologies at an early stage we can help them make the most data-informed decision possible. We can then implement a seamless program of work that integrates drug substance synthesis and manufacturing into our Translational Pharmaceutics platform to provide time and cost savings.

Have you noticed increased interest in the development of more targeted drugs?

Approximately 50% of drugs approved by the FDA over the past five years have been for orphan/rare disease indications. This presents a unique challenge and opportunity to the industry, as historically service providers and pharmaceutical companies looked for big blockbuster drugs that would be prescribed to millions of patients. Today, patient populations are becoming more targeted with an increased focus on rare diseases. To support this, supply chains must be more flexible. When we manufacture a product, the customer then delivers it to patients, either in clinical trials or on the market. In the case of products for orphan diseases, the customer can either make a significant upfront investment and manufacture a large amount of product with an extended shelf life, or wait until patients have been recruited and deliver the product on an almost just-in-time basis. Quotient Sciences has created the protocols and methodology to just-in-time manufacture, package, label, ship and deliver product to clinics within a two-week time frame. With this model, managing the supply chain and logistics is fundamental. We are currently looking at acquisition targets that will help us bridge more firmly into this space, given our belief that just-in-time manufacturing will play an integral part in the future of drug manufacturing, specifically in more specialized and targeted therapeutic areas.

At what stage of the drug development process is the element of speed or integration most critical to customers?

Our principal focus is on the early phases of drug development, from the point of candidate selection through to proof of concept. Through the eyes of a drug developer, this phase of development is loaded with risk. This process is more difficult if the customer is working with multiple outsourced parties. The focus of our integrated Translational Pharmaceutics programs is to provide the customer with a development platform capable of responding in real-time to emerging development data and maintain an overall timeline to proof of concept.

Quotient Sciences is investing US$8 million into expansion efforts for in-house API synthesis and manufacturing. What is the company’s goal with this investment?

We have seen increased demand towards local API production in both the US and the UK due to supply chain challenges caused by the pandemic and geopolitical issues. Our API capacity expansion will allow us to manage the drug substance and drug product supply chains in-house for our customers and ensure that APIs are supplied on time and at the right quantity and quality to drive the development program.

Q: What important company milestone do you anticipate reaching in 2022?

A: As an organization, it is starting to feel like we have overcome the disruption that arose from the COVID-19 pandemic these past two years, and we are looking forward to maintaining our growth momentum during 2022. We continue to win new customers and broaden the portfolio of exciting new molecules that we are helping to develop. In response to this increasing demand, we will conclude major facility expansion programs at our key operating sites in both the U.S. and U.K. in the next 12 months. These expansions will deliver new capabilities that can be fully integrated into our services portfolio and increase capacity for our existing services — all of which are part of our continued commitment to expand and innovate our offering to support our customer’s drug programs.

Continue reading what Mark and others have to say in this feature from Pharma's Almanac.

Read the full article

Mark Egerton, CEO of Quotient Sciences was recently asked to contribute to a piece with Pharma's Almanac, entitled 'What’s the key to being a leader in the industry?'

Q: What’s the key to being a leader in the industry?'

Mark Egerton, Ph.D., Chief Executive Officer, Quotient Sciences
A: When I think about being a leader in our industry, I think about being a role model — one that inspires others to focus on the greater purpose that we serve and one who drives positive change. Developing new medicines with the potential to improve the quality of life for patients in need is an incredibly rewarding purpose and an important responsibility. This is why Quotient’s manifesto is focused on exactly that: “Molecule to Cure. FAST.”

The leaders that I admire have consistently had this focus at the front and center of their vision as their North Star. I’m fortunate to be surrounded every day by great leaders in Quotient and at our customers. Importantly, such leaders are not dictated by their position in an organizational hierarchy. They are colleagues that come from anywhere in the business and have the vision to deliver a real positive impact that is so powerful that it inspires those around them to mobilize and support. Strong leaders maintain that passion when things don’t always work out, which, unfortunately, we know happens all too frequently in drug development. But when it does work out, it’s an incredibly fulfilling experience.

Read the full piece here

Mark Egerton, CEO, Quotient Sciences: Interview with Global Business Report

Q: How was 2021 for Quotient Sciences, particularly within the US?

A: In February 2021, Quotient Sciences expanded its portfolio of services to include drug substance and bioanalysis capabilities by acquiring the Alnwick facility from Arcinova, a UK-based CDMO. Over the past year we have been focused on fully integrating these capabilities into our core Translational Pharmaceutics platform, saving our customers significant time and costs by integrating drug development and clinical testing services within a development program under a single clinical protocol. We also went through a series of organic investments at five of our seven sites, where we have been increasing drug substance, clinical trial manufacturing, and clinical testing space. These investments have either been completed or are ongoing and will be completed in 2022.
In recent years, there has been phenomenal investment in pharmaceutical R&D, and the number of molecules continues to grow. Aligned with this increase, Quotient Sciences’ customer base has grown to approximately 500 customers across the US and Europe. We have operating sites in both the UK and the US, but 80% of our revenues are generated from US-based customers.

Q: Can you explain the importance for drug developers to have a CDMO that can manage both drug substance and drug product in parallel?

A: Quotient Sciences wants to support our customers with their molecules earlier in the development process, from the point at which the drug candidate molecule is selected from the discovery program. By incorporating our scientific expertise and development technologies at an early stage we can help them make the most data-informed decision possible. We can then implement a seamless program of work that integrates drug substance synthesis and manufacturing into our Translational Pharmaceutics® platform to provide time and cost savings.

Q: Have you noticed an increased interest in the development of more targeted drugs?

A: Approximately 50% of drugs approved by the FDA over the past five years have been for orphan/rare disease indications. This presents a unique challenge and opportunity to the industry, as historically service providers and pharmaceutical companies looked for big blockbuster drugs that would be prescribed to millions of patients. Today, patient populations are becoming more targeted with an increased focus on rare diseases. To support this, supply chains must be more flexible. When we manufacture a product, the customer then delivers it to patients, either in clinical trials or on the market. In the case of products for orphan diseases, the customer can either make a significant upfront investment and manufacture a large amount of product with an extended shelf life, or wait until patients have been recruited and deliver the product on an almost just-in-time basis. Quotient Sciences has created the protocols and methodology to just-in-time manufacture, package, label, ship and deliver product to clinics within a two-week time frame. With this model, managing the supply chain and logistics is fundamental. We are currently looking at acquisition targets that will help us bridge more firmly into this space, given our belief that just-in-time manufacturing will play an integral part in the future of drug manufacturing, specifically in more specialized and targeted therapeutic areas.

Q: At what stage of the drug development process is the element of speed or integration most critical to customers?

A: Our principal focus is on the early phases of drug development, from the point of candidate selection through to proof of concept. Through the eyes of a drug developer, this phase of development is loaded with risk. This process is more difficult if the customer is working with multiple outsourced parties. The focus of our integrated Translational Pharmaceutics® programs is to provide the customer with a development platform capable of responding in real-time to emerging development data and maintaining an overall timeline to proof of concept.

Q: Quotient Sciences is investing US$8 million into expansion efforts for in-house API synthesis and manufacturing. What is the company’s goal with this investment?

A: We have seen increased demand towards local API production in both the US and the UK due to supply chain challenges caused by the pandemic and geopolitical issues. Our API capacity expansion will allow us to manage the drug substance and drug product supply chains in-house for our customers and ensure that APIs are supplied on time and at the right quantity and quality to drive the development program.

Read the full article

Mark Egerton, CEO of Quotient Sciences has been featured in and article in Global Business Reports: A Shifting Landscape The outsourcing model is here to stay

In addition to speed, clients also want ease. Rather than working with several service providers along a product’s lifecycle, for example, it is much easier to work with just a few. To streamline the drug development process, Quotient Sciences’ CEO Mark Egerton sees value in CDMOs managing both drug substance and drug product in parallel. “Previously, customers would use service providers upstream from us and make decisions on which compounds to progress without much consideration of what would happen downstream,” explained Egerton. “The customer would sometimes manufacture the drug substance only to find out later they had made an error in the compound selection process. Having already made significant investment, they are reluctant to take a step back and thus start to make compromises for their downstream development plan.”

Read the full article 

Mark Egerton, CEO of Quotient Sciences has been featured in and article in Global Business Reports: "Keeping Up With Demands: CDMOs diversify their capabilities to meet their clients’ complex requirements."

"According to Mark Egerton of Quotient Sciences, pharmaceutical companies developing drugs to treat rare disorders have two options in terms of distribution. They can either invest substantially into producing large quantities of product with an extended shelf life or hold off until patients have already been recruited and then deliver the drug to this population in a near just-in-time fashion. The latter is often attractive when dealing with patient populations so small that the recruitment process for trials can be a long and unpredictable journey."

Read the full article 

In this roundtable with Pharma's Almanac, Mark Egerton, CEO of Quotient Sciences, answers the Question 'What’s the key to being a leader in the industry?

Featured Roundtable Interview with Mark Egerton, CEO of Quotient Sciences with Pharma's Almanac

Q: What’s the key to being a leader in the industry?

A: When I think about being a leader in our industry, I think about being a role model — one that inspires others to focus on the greater purpose that we serve and one who drives positive change. Developing new medicines with the potential to improve the quality of life for patients in need is an incredibly rewarding purpose and an important responsibility. This is why Quotient’s manifesto is focused on exactly that: “Molecule to Cure. FAST.”

The leaders that I admire have consistently had this focus at the front and center of their vision as their North Star. I’m fortunate to be surrounded every day by great leaders in Quotient and at our customers. Importantly, such leaders are not dictated by their position in an organizational hierarchy. They are colleagues that come from anywhere in the business and have the vision to deliver a real positive impact that is so powerful that it inspires those around them to mobilize and support. Strong leaders maintain that passion when things don’t always work out, which, unfortunately, we know happens all too frequently in drug development. But when it does work out, it’s an incredibly fulfilling experience.

Read the full article