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Bioanalysis at Quotient Sciences - Q&A with Stuart McDougall

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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 preclinical to Phase I.  To best support our customer’s 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 40years 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 customer’s 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 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-kg 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’s 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 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. For more information on our preformulation and material sciences capabilities, click here.

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 its spray dried dispersions (SDD) 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: A wide range of analytical techniques are available to fully characterize solid state forms including:
    • X-Ray powder diffraction (XRPD)
    • Thermal Analysis (DSC, TGA)
    • Hygroscopy (DVS)
    • Hot stage microscopy
    • Particle size distribution and particle enumeration
    • Surface Area
    • Solution and Solid State NMR
    • FT-IR
    • Dissolution/disintegration
GMP & non-GMP manufacturing

Our facilities can provide both GMP and non-GMP drug substance manufacturing with the ability to generate kg per day quantities.

Current 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 offgassing measurement capability
  • Onsite 100L reactors, fully operational in 2021
  • A range of isolation and drying options, including mobile filter dryers (316 Stainless Steel and Hastelloy MOC) with up to 15 kilogram capacities.
  • Containment systems for handling compounds up to and including Safebridge Band 3.
KILO Lab/Pilot Plant Manufacture

Quotient has access to additional scale up and pilot plant assets to complement our on-site facilities with  a capacity range between 50 L and 1300 L capable of producing 5-100 kg in batch. We have a range of internal manufacturing assets (batch, CSTR, trickle bed and plug flow) from multigram to multikilogram capacity (multitonne p.a capability).

The combined offering allows Quotient to meet our customer’s drug substance requirements from preclinical through to full scale commercial phases. The scale up process is executed by a highly experienced manufacturing team, providing our customers with a secure source of supply for technically challenging projects.

Our investment in innovative and flexible modular manufacturing technology will further enhance our capabilities. The technology enables us to quickly configure reactors for drug substance (API) manufacture and then rapidly reassemble reactors for the next project.

Stability testing

Stability testing provides evidence of how time and changes in the environment affect the quality of a drug substance. It is used to establish a re-test period for the drug substance and to determine the most suitable conditions for storage.

At Quotient, we produce high quality stability data through a combination of analytical, microbiological and materials 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.

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