Putting a drug through process optimization will help to identify the most efficient and commercially viable route without compromising the quality and safety of the end product. Through the careful refinement of the process steps used to manufacture a drug substance or active pharmaceutical ingredient (API), process optimization will play an integral part in improving product yield while reducing costs and processing times.

 

Process optimization is an important part of risk management throughout the drug development process. Pharma organizations will heavily invest in the development of promising drugs, in the hope of reaching commercialization. However, a major challenge is ensuring that drug manufacturing is fit for purpose, as what may appear to be a promising drug on a lab scale does not always translate into an appropriate commercial process. This is where drug developers can utilize the support and services from Contract Research Organizations (CROs), as shifting pharmaceutical trends and industry pressures have resulted in an increased reliance on the outsourcing of various tasks.

 

Partnering with a knowledgeable CRO with specialized expertise in process development and optimization can help to minimise the risk of manufacturing issues, both during development and post-launch, and thus improve return on investment (ROI). Subjecting a drug candidate to a scientifically rigorous scale-up and optimization programme can help to refine assets and increase their value.

 

Batch failure is a particularly high risk in the pharma industry, especially in development manufacture. One study reported sigma levels, a statistical tool used to measure the number of defects per million opportunities, often standing at two for pharma (308,537 defects per million opportunities), compared to the six cited for industries including electronic, communication and automobile (3.4 defects per million opportunities).¹ This high rate of failure is largely due to the linear model of drug development that many companies follow. Optimizing processes to better define the operating envelope through synergistically evaluating steps in parallel, rather than sequentially, will help refine manufacturing processes and lower the risk of batch failure.

 

If good process optimization can help to reduce the risk of both asset and manufacturing failure, then why isn’t there a standard approach from both pharma companies and outsourcing organizations? Companies may not always believe it will improve the net present value of their assets, due to the investment of time and money required. CROs who want to help reduce risk throughout the manufacturing process should ensure that drug developers are aware of the merits that process optimisation can bring as a long-term investment, and how it can be pragmatically incorporated into the drug development process to manage cost.

 

Outsourcing organizations must therefore deliver a consultative and pragmatic approach when undertaking a customer’s project in order to deliver appropriate results. It is imperative to understand the constraints, whether financial or other, that customers face when taking their drug through the development pipeline. Through knowledgeable communication and developing a strong relationship between both customer and organisation from the start of a project, a realistic chemical process development and optimization strategy can be implemented, effectively balancing customer priorities, investment and risk reduction.

 

As well as understanding the challenges and pressures faced by a customer, a CRO’s involvement in a project is also wholly dependent on the stage of drug development – affecting how they approach process optimization for a customer’s molecule. At an early time point, such as the initial nomination of a candidate to take to the clinic, there is a focus within process development on investigating the safe scalability and speed of material delivery, and the appropriate quality of the drug product. In contrast, towards the end of the drug development project, there is often a greater focus on environmental sustainability and cost of goods. Both are equally important, and fundamentally rely on a customer’s specific project requirements. 

 

The services provided by CROs will continue to shape the future of pharma, as demand for outsourcing continues to grow at a seemingly unstoppable pace. Emerging trends, such as improving automating workloads and using predictive technology, will allow CROs to further improve their efficiency as they work their way through the pharmaceutical value chain. However, the main driving factor for chemical process optimization will continue to be using rigorous scientific method based on experience and expertise to create robust and comprehensive manufacturing processes that help to de-risk the process of drug development.