Bioanalysis is a critical part of drug development. From drug discovery, through to pre-clinical and clinical studies, understanding drug exposure, safety, and metabolism are essential in accelerating drugs to clinic and commercialization. In this article, we talk to Paige Bellis, Head of ICP-MS Bioanalytical Operations, to find out more about ICP-MS capabilities and the bioanalytical team at Quotient Sciences.

What is your background and your current role at Quotient Sciences?

I joined Quotient Sciences six years ago as a Bioanalyst after graduating from Northumbria University, where I studied Biomedical Science. As a Bioanalyst, I processed samples through ICP-MS, LC-MS, and GC-MS, and later had the responsibility of leading ICP-MS and LC-MS studies when I took on the role of a Responsible Scientist. I later moved to a role in Project Management where I managed large-scale projects with multiple vendors and also learned more about other departments within Quotient Sciences. 

Recently, I was appointed as the Head of ICP-MS Bioanalytical Operations and manage the Bioanalytical ICP-MS team. Part of my role is to lead, develop, and coach the Responsible Scientists and Bioanalysts to deliver ICP-MS customer projects successfully. I also act as the Project Manager for all ICP-MS projects to deliver client objectives in a timely and accurate way.

How is the bioanalytical ICP-MS team structured at Quotient Sciences? 

The bioanalytical ICP-MS team is an expert group at Quotient Sciences that includes a cross-functional team of scientists who can support an entire study. Each team member brings a wealth of insight to every project we work on, some with decades of experience working in industry. 

Stuart McDougall is our Bioanalytical Principal Research Fellow with over 30 years of experience in the field. He has actively participated as a member of the European Bioanalytical Forum (EBF) and the American Association of Pharmaceutical Scientists (AAPS) for many years. In 2022, he contributed to the EBF’s workshop and corresponding sessions discussing the implementation of ICH-M10, a new guideline that went into effect in January 2023. This was an important milestone because it unified and harmonized the existing regional guidelines (e.g. FDA, EMEA, PMDA, ANIVSA, etc).

Our Method Developer has over a decade of experience and is responsible for developing robust and precise ICP-MS methods for quantitative measurement of the target element in biological matrix. Some of the challenging projects we have faced have included total copper and arsenic speciation, and quantitative tissue analysis.  

Once the method has been developed, our Bioanalysts play a critical role in validating the elemental assays following ICH-M10, and support both clinical and non-clinical sample analysis using industry-leading ICP-MS and ICP-MS/MS instrumentation. Bioanalysts work closely with our Responsible Scientists, who direct projects to ensure we provide regulatory-compliant data for our customers.   

Aside from adherence to ICH-M10 guidelines, in what other ways does Quotient Sciences ensure compliance with global regulatory standards?

Our bioanalytical laboratory is located within the Quotient Sciences – Alnwick facility. It is routinely inspected by the UK MHRA for compliance with Good Laboratory Practice (GLP) and Good Clinical Practice (GCP) standards. We have supported many customers who have submitted their bioanalytical ICP-MS data to regulatory authorities including the  US Food and Drug Administration (FDA) and have successfully registered their new drugs. 

Last year, the US FDA audited three bioequivalence studies at Alnwick for a renowned pharmaceutical company during an unplanned, study-specific inspection. The FDA inspection and audit were successful. 

The bioanalytical ICP-MS team is an expert group at Quotient Sciences that includes a cross-functional team of scientists who can support an entire study. Each team member brings a wealth of insight to every project we work on, some with decades of experience working in industry. 

Are there more specialized capabilities available, and in what cases would they be used? What have been some common, as well as some of the more uncommon, requests from customer programs? 

We support a range of studies, from pre-clinical to Phase III clinical trials, by ICP-MS. Our team have validated many preclinical and clinical assays in many matrices including blood, plasma, urine, faeces and tissues. Those assays have been used to analyse samples for dose-ranging studies, GLP toxicology studies, and many clinical studies.

For New Chemical Entities (NCE) that can not be readily measured by conventional assays such as LC-MS, but contain a unique element, Quotient Sciences have been able to provide ADME for drug development programs (Elemental ADME). As part of this we can also support elemental profiling and speciation using LC-ICP-MS to determine biotransformation. And for complex samples that require additional homogenisation, such as tissues, food  or excreta, we have both mechanical (bead, ultrasonic, Turrax and Stomacher) and high-capacity Ultrawave microwave digestion capability.  

We have extensive experience with quantitative elemental analysis for both PK endpoint (elements in drugs) and PD biomarkers, monitoring changes in element levels in disease states and after treatment. The team has experience analysing many elements, ranging from antimony to zinc. This experience enables us to collaborate with our customers to solve challenges and produce high quality data on time to achieve the best outcome for the project.

Learn more about bioanalysis capabilities at Quotient Sciences.

Despite incentives in both the US and EU for developing orphan drugs for rare diseases, many conditions do not have approved or suitable treatments available. 

Many rare diseases impact children and can be fatal in infants and early childhood, making the need for new treatments even more critical. This article discusses how strong partnerships between drug developers and integrated contract research, development, and manufacturing organizations (CRDMOs) are vital for advancing treatments for rare and pediatric diseases.

In the US, rare diseases are defined as those affecting fewer than 200,000 people, and according to the EU definition, rare diseases affect fewer than five in 10,000 people [1, 2]. Many rare diseases are genetically inherited conditions and can include forms of full or partial blindness, hemophilia, and liver disease, as well as certain forms of cancer. Patients living with a rare disease often struggle with diagnosis of their condition, since a rare disease may come with broad symptoms that make it difficult to distinguish between diseases or between patients having the same disease. Some patients may even be misdiagnosed throughout their lifetime, and it may take years and multiple visits to health care providers (HCPs) and specialists to find suitable treatment options – if any do exist.

Since the passing of the Orphan Drug Act into law in the United States in 1983, the FDA has approved hundreds of drugs for rare diseases in the past four decades. Last year, the FDA approved 28 new therapies for orphan/rare indications, amounting to half of the new drugs approved [3]. Similar regulations also exist in the EU, but despite the incentives in both regions many rare diseases do not have approved or suitable treatments available. Constrained R&D budgets, challenging product development, and clinical recruitment, and reimbursement negotiations are among the obstacles faced by drug developers. Another reality of rare diseases is that many are prevalent in children, requiring additional time and cost to develop age-appropriate and palatable dosage forms.

Selecting the right development partner can be crucial to ease the burden of drug development for these therapies and increase the likelihood of achieving market success in orphan/rare drug development. And because many rare diseases impact children and can be fatal in infants and early childhood, the need for new treatments is even more critical.

When selecting an optimal contract research, development, manufacturing, and service organization (CRDMO) partner, the availability of integrated chemistry, manufacturing, and controls (CMC) and clinical research services from one company can be invaluable to streamline drug development processes. Additionally, the expertise of the CRO/CDMO can make all the difference in the development of age-appropriate liquid and solid dose formulations that are easier for infants and children to swallow, as well as lend expertise in complex drug programs. These can include different drug formulations such as solutions, suspensions, powder for reconstitution, and minitablets, and the taste and palatability challenges of these forms need to be overcome and confirmed by taste assessment studies.

Case study: Clinical assessment of Maralixibat for rare pediatric liver diseases via real-time personalized GMP manufacturing

Alagille Syndrome (ALGS), an autosomal genetic disease, and Progressive Familial Intrahepatic Cholestasis (PFIC), a group of cholestatic conditions, are both forms of rare pediatric liver diseases. Maralixibat is an oral small-molecule ileal bile acid transporter (IBAT) inhibitor that was first approved by the US FDA in 2021 for the treatment of cholestatic pruritus in patients with ALGS, ages 1 and older [6].

In its development, Quotient Sciences worked with the client on a high level of customization of the drug product to support an extensive Phase II/III clinical program based on mg/kg dosing of patients. The client had the potential need to adapt the product during the treatment phase if there was a change in body weight of >10%.

A real-time adaptive platform was configured by Quotient Sciences that enabled a personalized solution product to be manufactured, labeled, and supplied globally, ready for dosing within 1-3 weeks of subject eligibility being confirmed. Products were re-supplied to each patient every 1-3 months based on individual needs and response to treatment. In total, six studies were supported involving manufacturing over 2,000 individual products for dosing in over 180 patients across 27 sites in 9 countries.

As of March 2024, Maralixibat is now also approved by the FDA for the treatment of cholestatic pruritus in patients ages 5 and older with progressive familial intrahepatic cholestasis (PFIC) [4], offering new treatment options for pediatric patients. 
 

References

1. The Orphan Drug Act: Implementation and Impact (OEI-09-00-00380; 5/01) (hhs.gov)
2. Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (legislation.gov.uk)
3. FDA Approves Many New Drugs in 2023 that Will Benefit Patients and Consumers
4. Mirum scores 2nd FDA nod for rare liver disease drug Livmarli, this one to treat PFIC 

Pictured left to right: Dr. Andrew Lewis, Kieron Hall, Eric Bironneau

NOTTINGHAM, UK; 18 March 2024 – Drug development and manufacturing accelerator Quotient Sciences has announced major changes to its commercial and scientific executive leadership team, strengthening its position as a global leader in the sector.

New appointments include Dr. Andrew Lewis as Chief Scientific Officer, Kieron Hall as Chief Marketing Officer, and Eric Bironneau as Chief Business Officer who will each play a critical role in Quotient Sciences growth and strategic direction.
In his new role as Chief Scientific Officer, Dr. Andrew Lewis has responsibility for the company’s scientific and technological innovation. Andrew will lead the team of Drug Development Consultants and Scientific Research Fellows to grow Quotient Sciences’ global scientific expertise and recognition.

During his eight years with Quotient Sciences, Andrew has held various scientific leadership positions, most recently as Senior Vice President, Pharmaceutical Development. Prior to joining Quotient Sciences, Andrew was Director of Novel Drug Delivery Technologies at Ipsen.

Kieron Hall’s appointment as Chief Marketing Officer will see him lead the company’s strategic and growth initiatives and marketing organization. Kieron has been with the company in various global commercial leadership positions for more than 16 years, including Chief Commercial Officer. He was Head of Business Development in Europe for Cyprotex (an Evotec company) before joining Quotient Sciences.

Eric Bironneau has joined the company as Chief Business Officer, with responsibility for Quotient Sciences’ commercial organization across drug substance, drug product, and Translational Pharmaceutics® commercial lines, as well as for Quotient Sciences’ strategic partnerships. Eric      brings over two decades of commercial leadership experience to the company, including serving as Vice President, Global Sales & Business Development at Axplora and Novasep.

These latest changes come off the back of Thierry Van Nieuwenhove joining the company as CEO last October succeeding their long-standing leader Mark Egerton, who retired after 18 years with the company.

“We are committed to continuing our strategy of accelerating drug development, bringing new medicines to patients faster by breaking down traditional industry silos and leading with a science-first mindset for how we deliver customer programs,” said Thierry Van Nieuwenhove, CEO of Quotient Sciences. “I am excited to work with Andrew, Kieron, and Eric in their new roles, along with the rest of our leadership team, to continue to grow Quotient Sciences as a global leader in drug development.”