Process Research & Development

01. Route Development

Often, target compounds have only ever been made in low milligram quantities and the original route is not appropriate for production of larger quantities of material within a quality manufacturing environment. As such processes need to be developed, and in some cases redesigned completely.

Our R&D phase encompasses initial route scouting activities and early process development, demonstrating the feasibility of a given route for onward development activities.

02. Process Development

The development of chemical processes takes place across a range of scales, and it is important to understand the key project attributes from the outset so that a phase-appropriate development can be undertaken. With an overarching aim of Quality Manufacture, our process research and development activities involve a pragmatic approach, understanding what is critical to your project.

The correlation between process parameters and reaction outcome is probed during the development and optimisation phase, allowing for a much deeper understanding around a particular chemical event. Key to this phase of work are strong analytical capabilities and an attention to detail, as an understanding of process impurities becomes critical.

With the aim of generating a proof-of-concept batch, scale up is undertaken in a safe and cost-effective  manner, with the ultimate aim of delivering a robust, reproducible and reliable process.

03. Analytical Development

Analytical development is a continuous process and should closely follow synthetic development. As impurity profiles change when processes are modified, analytical methods may need to be altered to accommodate these changes. The understanding of process impurities is critical to any product manufactured within a Quality environment, and impurities will need to be identified, quantified and controlled, as batch to batch variation of these impurities may result in a detrimental performance of the final product.

We carry out a risk assessment of the total process to determine the impurities that may be present and the associated impact that may have on your target material. This enables specifications to be defined and in turn the analytical methods that will be required. HFR has experience in the development of analytical methods suitable for assay and related impurities, and the subsequent validation of these methods to ICH standards.

04. Traceable Manufacture

Traceable Manufacture is our ISO9001 quality level which can be applied across different projects or sectors. Traceable manufacture provides consistency in product synthesis and impurity profile, which gives our partners confidence that the materials we provide are the same each and every time.

Should a project progress through to cGMP production, traceable manufacture gives an opportunity to iron out any technical issues associated with the synthesis and develop appropriate analytical methodology prior to the full GMP phase.

05. GMP Manufacture

Our value proposition is a combination of scientific excellence and quality. Since 2007, we have been audited by the MHRA for the production of materials to cGMP standards for both phase I and phase II clinical trials, and our GMP phase is carried out in accordance with the principles of cGMP as promulgated under European Union Rules governing Manufacture of Medicinal Products for Phase I/II Clinical Trial, EU guide to GMP Eudralex Vol 4 part II section 19 ‘Basic Requirements for Active Substances used as Starting Materials’.

Having built a solid relationship with our client by this point, we work together to develop a risk assessment and define a suitable GMP starting point for the process. GMP production is conducted in our ISO class 8 clean rooms by dedicated GMP chemists, with full QA oversight, generating material of high quality with all associated regulatory paperwork.

06. Stability Studies

The manufacture of any product, whether under HFR’s Traceable or GMP manufacture systems, requires an understanding of substance stability. HFR carry out both accelerated and long-term stability studies to ICH-guidelines, giving an insight into the storage conditions and shelf-life of an individual product.

Initial stability studies are carried out on material generated as the ‘proof-of-concept’ batch or ‘validation’ batch, which is representative of the final product batch for all future manufacture.