Powerful new connections

Dr David Griffiths provides an insight into a fast-growing company that has brought together well-known specialists in radiochemistry, metabolism, bioanalysis and biomarkers, early and specialist clinical trials, and microbiology, to provide a unique portfolio of solutions relevant to today’s product development.

Despite the talk of ‘drug discovery in crisis’ and few new drugs reaching the market in recent years, the field is still full of opportunities. The drive towards personalised medicine, a new emphasis on the co-development of diagnostics and therapeutics and the potential of biologics are all changing the development paradigm. All this is having a major impact on programme timelines and the structure and goals of drug development. Understanding pharmacokinetics and metabolism, monitoring biomarkers and utilising bioanalysis are taking centre stage. Early-phase trials with complex multiple endpoints are growing in importance.

Into this new environment steps Quotient – a powerful group of specialists in radiochemistry, metabolism, bioanalysis and biomarkers, early and specialist clinical trials, and microbiology. The company’s proven expertise and comprehensive range of services for drug development can be used individually to support a oneoff project or connected to add value and deliver critical insight to the most complex scenarios.Working to GLP, GMP and GCP, Quotient has invested in science and technology platforms as well as integrated API/ IMP formulation and manufacturing facilities that can feed directly into its in-house Phase I facility. Regulatory, safety and project management issues can be streamlined within a single organisation. The approach significantly reduces complexity and can shorten project time lines.

A deeper understanding
A specialist team of synthetic chemists, analytical chemists and experts in compound radiolabelling are a key part of Quotient’s Synthesis-to- Clinic™ approach for clients engaged in studies relying on radiolabelled compounds. Linking this with drug metabolism (clinical and nonclinical), pharmacokinetics and bioanalytical sciences creates a unique partner for drug discovery and development. The integrated Synthesis-to-Clinic service is an excellent example of how Quotient can integrate its speciality capabilities to streamline drug development for its clients (see Figure 1). By removing the need to coordinate multiple vendors, this approach simplifies and de-risks the outsourcing of 14C-enabled drug development programmes.

Custom synthesis of carbon- 14 and tritium labelled compounds – integrated with metabolism and clinical studies – is at Quotient’s core. The acquisition of Amersham Radiolabelling Services from GE Healthcare reinforces this commitment. Quotient has the facilities to support a client’s GMP activities, embracing APIs and IMPs, including parenteral dose forms. Comprehensive compound data sheets and radiosynthesis reports are provided. APIs are synthesised for use in a range of in vitro and in vivo studies, including human AME studies, ivMicrotracer™ and Phase 0 microdosing protocols. IMPs (solutions, liquid dose forms and solid dose forms) are prepared for clinical trials use. Quotient’s RapidFACT™ and Enterion™ platforms also offer clients the potential to accelerate reformulation development where PK issues have been identified, as well as optimise formulation development for future clinical trials.

Quotient applies its broad experience of synthetic route development, gained in custom isotope synthesis, to conventional organic synthesis and develops novel laboratory-scale routes to potential drug candidates. Furthermore, the team prepares stablelabelled compounds for use as internal standards in bioanalysis. Connecting this radiochemistry expertise directly with metabolism services provides advantages in handling, analytical and chemical understanding of the molecules being studied, as well as potentially reducing project timelines.

Quotient’s metabolism services have been developed to embrace US Food and Drug Administration (FDA) thinking on understanding the enzymology of drug metabolism, the role of transporters and active metabolites, as well as the more traditional absorption, distribution, metabolism and excretion studies. This has included investments in state-of-the-art metabolite identification capabilities, low-level radioactive counting expertise, validation of drug transport models and development of reactive metabolite assays. Experience in working closely with sponsors taking compounds through FDA NDA/IND approval processes now informs priorities and the order in which studies are completed during drug development.

Pioneering biomarkers and microbiology
World-class expertise means that Quotient is a true pioneer of bioanalysis, biomarkers and microbiology. With one of the largest bioanalytical facilities in Europe and particular strength in mass spectrometry and immunochemistry, the company is a leading specialist in the analysis of small molecule drugs in biological fluids. As biomarkers form an increasingly important part of the drug development process for small molecules and biologics, Quotient works with established biomarkers, undertaking proprietary screening, new biomarker discovery and bespoke method development. Its specialities include biomarker method development – feasibility assessment, establishing methods and development; experience with a variety of analytical methodologies, species and matrices; synthesis of immunogens and generation of antibodies, complete with in-house characterisation and experience in supporting biomarker discovery; validation of biomarker methods – in-house and commercial, to GCP/GLP standards; and biomarker quantification – as a measure of drug safety or efficacy or to prove a new drug’s mechanism.

The Quotient team has developed and adopted new bioanalysis technology in other areas. A BioMS™ service, Gyrolab™ and MSD™ technology, as well as electrophoresis, affinity chromatography, mass spectrometry and fluorescence / chemiluminescence / radiolabel techniques all form part of the service options. The company has more than 20 years’ experience in specialist microbiology services for drug development. Purposebuilt facilities, including a Containment Level 3 Laboratory, and experienced staff provide the best environment for development of antimicrobials, and allow Quotient to support fully the microbiology needs of other development or life-cycle management programmes. In addition, national, regional or international antimicrobial surveillance studies using quantitative, standardised and internationally recognised methods form part of the company’s routine work.

Discovery and preclinical services extend through study design and development to investigating mechanisms of antimicrobial action and testing, using an extensive in-house culture collection that includes common as well as atypical and drugresistant strains. Quotient is internationally recognised – an active industry member of the Clinical and Laboratory Standards Institute of the US and working to the British Society for Antimicrobial Chemotherapy and other European guidelines.

Figure 2: Patented Enterion capsule and gamma scintigraphic imaging.

Innovation in the clinic
Combining the expertise and facilities of two of Europe’s leading Phase I clinics, Quotient specialises in early development services, with innovative technologies and expertise to accelerate the development process from First-in-Human (FiH) studies through to early Proof of Concept. With integrated GMP manufacture and GCP facilities, Quotient enables the development of a novel approach to optimising a drug product for clients. The company’s Translational Pharmaceutics™ platform integrates formulation development, drug product manufacture and clinical testing. The time to develop a new drug product is halved using this approach. Importantly, the drug product is optimised within a clinical protocol in response to emerging scientific data. Patented Enterion™ capsule and gamma scintigraphic imaging technologies (see Figure 2) provide critical insights into drug delivery and formulation performance. Across its clinical facilities in the UK Quotient has access to a population of approximately 8 million subjects who can be employed for early proof of concept studies. A range of patient groups, covering all major therapeutic areas of interest to the pharmaceutical industry, can be recruited. As a whole, Quotient has a vision of the future of drug development and is proud to be delivering a flexible service, high quality data and significant insight to clients around the globe.

Author

Dr David Griffiths is business development director at Quotient Bioresearch.

Company profile

Quotient’s specialist focus on radiochemistry, metabolism, bioanalysis and biomarkers, early and specialist clinical trials, and microbiology allows the company to significantly reduce complexity and shorten development time lines for its clients.

For more information, visit: www.quotientbioresearch.com.