From Drug Substance To Drug Product: Benefits of Working with an Integrated Services Provider
From Drug Substance to Drug Product: Benefits of working with an integrated services provider
Quotient Sciences is a drug development and manufacturing accelerator, providing customers with integrated drug substance and drug product solutions from the early stages of molecule selection and development through to the clinic and beyond (Figure: 1).
FIGURE 1: Quotient’s integrated offering. From molecule to market
Supporting Candidate Selection to First-in-Human
We engage with customers from the point of candidate drug selection, helping to ensure that the lead compound(s) can be manufactured in sufficient quantities to support initial toxicology and preclinical studies, while also being equipped to scale up the manufacturing processes to produce clinical drug substance to pharmaceutically acceptable standards (Good Manufacturing Practice: GMP). When developing a drug substance manufacturing process, the chemistry of the impurities generated is as important as the purity of the compound itself. We have a significant breadth of expertise in analytical sciences, enabling us to identify, quantitate and ultimately control the impurities generated in the manufacturing process. Small differences in impurities can have a profound impact on the toxicological profile of the compound.
At Quotient, we can support our clients by setting clinical phase-appropriate specifications, synthesising analytical reference standards, developing, and validating analytical methods all within one organization. We have hundreds of years of combined experience in synthetic route design, using the input of our highly qualified and experienced chemists and engineers to ensure that the shortest, most scalable and economic route to drug substance can be developed. As synthetic chemists we are constantly on the lookout for new technologies which could give us the option to significantly shorten and simplify the drug substance development process, taking stages of chemistry out of the process or enabling us to tap into commercially available raw materials which can be converted in a small number of synthetic steps to the target compound.
Recent additions to our technology portfolio include Synthetic Biology (particularly Biocatalysis) where we have several academic sponsored studentships running. A major technology drive has been in continuous manufacture using flow chemistry where we have a technology group in place and are running a three year INNOVATE UK program with the University of Nottingham. Flow technology for large scale chemical production is not new, however, recent equipment developments have enabled this to be applied on a much smaller scale. In principle flow technology involves running reagents and solvents through a high intensity process, usually with higher temperature and pressure in a pipe (plug flow) or continuous stirred tank (CSTR). Unlike the traditional batch process, flow involves the continuous feed of solvents and reagents through the reaction, minimizing the inventory of material (which can enable us to use hazardous reagents that we would not consider in batch) and generally leading to higher purity materials. A case study (Figure: 2) below demonstrates the application of flow to compress several processing stages for the manufacture of 6-hydroxynorketamine (6HNK), a new non-opioid depression treatment being developed by the US National Institute for Health (NIH). We were able to go from hours of processing time in batch to minutes in flow, with a radical simplification of the process, higher product purities and easier processing. More importantly we were able to process and deliver the material to the client much earlier in the clinical phase. The key takeaway is that Quotient Sciences is committed to technology development to enhance the velocity of drug substance delivery to our customers.
Bridging from Drug Substance to Drug Product
The drug substance / drug product interface is a key part of any successful drug development program. Where does drug substance end? Where do drug product activities begin? Who is responsible for the grey area in between? The activities relating to each are often the responsibility of different companies, or siloed departments of the same organization. This creates a number of downsides and inefficiencies, and the challenges are exacerbated when we consider the complexity of today’s molecules and target product profiles, with timeline pressures ever present.
A fully integrated drug substance and drug product manufacturing service results in a more efficient and accelerated development plan. Integrating all activities under a single organization encourages better workflows, processes, and builds close relationships between multidisciplinary experts. Process chemists can work alongside analytical and solid-state chemists to ensure rapid development and optimization of a drug substance. Formulation scientists and solid-state teams can together provide clear and unambiguous data for optimizing drug substance form, leading to rapid drug substance, dosage form design and drug product manufacturing.
There are multiple benefits of this approach to our customers, including:
• Timeline acceleration (minimum 2-3 months taken out of the drug development process)
• Ease of knowledge transfer (our drug substance team can rapidly transfer key analytical methodology to our in-house drug product teams, simplifying the overall analytical transfer process). Moreover, the team has > 30 years’ experience of analytical technology transfer
• Ease of materials transfer.
• Closer scientific links. We act as one integrated group and are managed across teams by one project manager, simplifying the communication between chemists, formulators, and clinicians
• We ensure that with our chemistry capabilities’, competence, and track record, and with our dedication to advancing new technology development, that drug substance delivery is removed from the critical path
• We bring a powerful combined offering as a source of advice for our clients for all aspects of the drug development process
• We give our clients the security of improved and flexible scheduling, simplifying the process and reducing the risk of outsourcing their drug development process from molecule to patient
The seamless coordination between drug substance and drug product manufacturing results in a more efficient and accelerated development plan. Integrating all activities under a single organization in an entirely non-siloed way encourages close relationships between multidisciplinary experts, creating a more agile approach to pharmaceutical development. However, the ultimate benefit is a significant shortening of the timeline from candidate selection to clinical development. On average drug development timelines will be reduced by 2-4 months, translating into significant R&D cost savings and shortens the faster provision of new medicines to patients.
For more information about Quotient integrated Drug Substance and Drug Product services, click here: http://www.quotientsciences.com/drug-substance