The difference between scaling up and just making bigger

The objective of our Process Development team at Avecia is to provide efficient, robust and scalable processes that can be used for clinical manufacture, process validation and beyond.

Key Activities

• delivery of process development projects at all stages of clinical development
• process validation support
• support of delivery of manufacturing projects

Development activities rely heavily on Design of Experiments (DoE). This can be described as a structured, organized method for determining the relationship between factors affecting a process.

Key Features of DoE

• limited number of experiments conducted - defined by the experimental program
• good quality data minimizes the requirement to repeat experiments
• large numbers of variables, and their interactions, can be assessed
• meaningful conclusions can be reached quickly

5 Steps to a better process......

A typical DoE approach, applied to a recent development project, is listed below:

• risk assessment process - potential variables identified
• factorial design and experimentation
• data analysis by ANOVA (ANalysis Of VAriance)
• experimentation to generate a response surface
• analysis of whole data set by ANOVA

Example of Output: Effect of changing two interacting variables on process yield - result applied directly to customer manufacturing campaign.

Development Output

• definition of process for manufacture and process development
• deep understanding of effects arising from changing a range of variables concurrently within the process design space
• move from NEW process to OPTIMISED and UNDERSTOOD process

Technology for today...........and tomorrow

Our R&D groups actively investigate all aspects of oligonucleotide manufacture, recent developments include:

• non-explosive activators
• new thiation reagents
• purification systems using aqueous solvents
• reagents to minimise side product formation during cleavage and deblock

We have also invested in the minimization of chlorinated solvents from our processes, thereby reducing their environmental impact.

For the future, we are always looking for ways of improving our manufacturing technology with particular focus on the development of new synthesis and purification methodologies.