Drug Substance

Quotient Sciences provides drug substance synthesis and manufacturing capabilities from candidate selection through to commercial production. With tactical deployment of best-in-class technologies, we minimize chemistry costs and move your drug substance supply off the critical path.

Our streamlined approach to developing drug substance has been shown to reduce manufacturing costs by 50% from pre-clinical to Phase I. To best support our customers' needs, we have made significant investments in technologies and equipment to meet the increasing demand for complex small-scale drug substance manufacture. With more than 40 years of experience in synthetic organic chemistry, coupled with extensive expertise in flow chemistry, synthetic biology, and biocatalysis, we can optimize manufacturing processes and save months of development time for our customers. We pride ourselves on quickly delivering high-purity drug substance and can rapidly scale up manufacture at our cutting-edge facilities. 

Our highly experienced chemistry, analytical, and drug development teams can support route selection, process development, critical process parameter (CPP) definition, experimental design (DOE), and impurity tracking/control, as well as developing bespoke and innovative solutions for our customers' technically difficult challenges.

We always strive to produce economical processes for high-purity drug substances that can be rapidly scaled from grams to multi-kilograms in our purpose-built development and manufacturing facility. 

Our Drug Substance Services

Process Research and Development

Highly trained and experienced Quotient Sciences chemists support all aspects of drug substance development, selecting and developing optimum synthetic routes for drug substance manufacture. We combine rapid route selection with the implementation of innovative technological solutions to produce the shortest, most efficient scalable pathway to a drug substance. Our focus is on process velocity and economy, product purity, process scalability, and safety. The drug substance can then be scaled to multi-kilogram quantities to support direct client supply, or as part of an integrated in-house drug substance/drug product package to support clinical trial or full-scale commercialization programs.

Quotient Sciences' philosophy targets optimal velocity for drug substance delivery, to ensure rapid drug substance supply for urgent clinical trial needs, while enhancing process efficiency and robustness to lower costs and generate higher purity. Our work also involves defining the best route for product manufacturing scalability.

Solid-State Services

Quotient Sciences has extensive expertise in solid-form screening and selection, with material scientists working closely with drug substance chemists to identify the most appropriate drug substance form for development. Learn more about our pre-formulation and material science capabilities.

Our capabilities include:

  • Salt Selection: Poor bioavailability or instability of a drug substance can often be solved/improved by screening different salt forms. The selection of the most appropriate salt can not only improve the physicochemical properties, but identifying all developable salts can strengthen the intellectual property of the drug substance. The choice of counterions is typically based on the pKa of the drug substance, the relevance for the expected dosage form, and the know-how of our experts.
  • Polymorph Screening: To meet regulatory requirements, the polymorphic behavior of a drug substance needs to be assessed and the polymorph chosen for development needs to be fully identified/characterized. Identifying the polymorph landscape can also strengthen intellectual property.
  • Amorphous Dispersions: Amorphous forms can have increased solubility and bioavailability in comparison with their crystalline form. However, crystalline materials tend to be more stable and amorphous material can recrystallize over time but can be stabilized as an amorphous solid dispersion. Whether it's spray-dried dispersions (SDDs) or hot melt extrusion (HME), our team of experts can support the enhancement needs of your molecule.
  • Crystallization Development: Supporting the drug substance development team, purification steps can be improved and drug substance manufacturing yield, throughput, and purity can be increased by integrating a solid-state approach to recrystallization processes.
  • Solid-State Characterization: Quotient Sciences offers a wide range of analytical techniques to fully characterize solid-state forms.
    • X-ray powder diffraction (XRPD)
    • Thermal analysis: differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)
    • Hygroscopy: dynamic vapor sorption (DVS)
    • Hot-stage microscopy
    • Particle size distribution and particle enumeration
    • Surface area
    • Solution and solid-state nuclear magnetic resonance (NMR) spectroscopy
    • Fourier-transform infrared spectroscopy (FT-IR)
    • Dissolution/disintegration
GMP & Non-GMP Manufacturing

Our facilities can provide both GMP (Good Manufacturing Practice) and non-GMP drug substance manufacturing, with the ability to generate kilogram-per-day quantities.

Our capabilities include:

  • 5-L GMP and non-GMP process chemistry facilities with full thermal control
  • 20-L GMP state-of-the-art reactor streams housed in dedicated walk-in fume cupboards with operating temperatures from -90°C up to +180°C
  • Full integration of reactor stream data logging to a dedicated server, enabling GMP monitoring of all key reaction parameters (pressure, temperature etc.) and real-time process optimization
  • State-of-the-art dedicated material storage area, enabling safe storage of a range of chemical classes and segregation of quarantine and released materials
  • Flexible continuous manufacturing units (FlowSyn, trickle-bed, and Salamander reactors with pressure capabilities up to 50 bar and operating temperatures up to 180°C) – these equipment trains have the capacity to generate kilogram quantities of materials per day
  • Automated parallel reactor streams with ReactIR and integrated calorimetry (HFCal) and off-gassing measurement capability
  • Onsite 100-L reactors
  • A range of isolation and drying options, including mobile filter dryers (316 stainless steel and Hastelloy MOC) with up to 15-kg capacities
  • Containment systems for handling compounds up to and including SafeBridge Band 3
Quotient Science's expertise provides the necessary labelled  materials tailored to support your studies.

Isotopic Labeling

Ensuring secure and rapid delivery of isotopically labeled (14C/stable isotope labeled) materials to support your non-clinical and clinical development.

At Quotient Sciences, we offer isotopic labeling services to support 14C human ADME studies and stable isotope labeling (SIL) for studying development candidates. Our team of experts provide guidance on the design and conduct of both non-clinical and clinical human ADME studies for research, development, and regulatory purposes. Through the use of mass spectrometry, our highly trained chemists are able to provide highly accurate measurements of test substances that aid in candidate development. Our radiochemists have extensive chemical and radiochemical knowledge and experience of isotopically labeling hundreds of molecular entities. They work closely with our analytical and drug product teams to deliver a solution-focused service to our customers throughout all stages of drug development, from candidate development to commercial.

We are experts in the safe handling of 14C-labeled high-potency/high-hazard compounds (cytotoxics) and 14C-labeled gases and volatiles, including 14CO2. Our facilities are UK Medicines and Healthcare products Regulatory Agency (MHRA)-accredited, and we offer full GMP synthesis of 14C-labeled compounds for human studies.

For more information on our isotopic labeling capabilities, click here.

Kilo Lab/Pilot Plant Manufacturing

Quotient Sciences has access to scale-up and pilot plant assets that complement our on-site facilities, featuring a capacity range between 50 L and 1300 L capable of producing 5-100 kg in batch. Our internal manufacturing assets (batch, CSTR, trickle bed, and plug flow) range from multi-gram to multi-kilogram capacity (multi-tonne per annum capability). Additionally, our investment in innovative, flexible modular manufacturing technology enables us to quickly configure reactors for drug substance (API) manufacturing, then rapidly reassemble reactors for the next project.

Quotient Sciences can meet drug substance requirements from pre-clinical through to full-scale commercial phases. The scale-up process is executed by a highly experienced manufacturing team, providing customers with a secure source of supply for technically challenging projects.

Stability Testing

Stability testing provides evidence of how time and changes in the environment affect the quality of a drug substance. At Quotient Sciences, we produce high-quality stability data through a combination of analytical, microbiological, and material science methodologies. Our service is supported by state-of-the-art facilities, including walk-in, ICH-compliant stability chambers and several smaller, reach-in units. ICH-compliant photo-stability testing equipment is also available to study the effects of light stress on materials and packaging.