Advanced process modelling for pharmaceuticals

Ten benefits of modelling and simulation for pharmaceuticals

Modelling and simulation provide many benefits in the design and operation of pharmaceutical processes. Here are our top ten:

Increase productivity and reduce costs associated with the development of new formulations
Model-based techniques provide a means to explore the design space rapidly and reliably to determine the best and most reliable processing options. Deployment of modelling early on makes it possible to reduce:

the time and cost of experimentation the time and cost of process development the operating and capital cost of the installed process.

thus improving R&D efficiency.

Improve operational performance and lower production costs

Model-based techniques can help you to improve the operational performance of reaction, crystallization, separation, agglomeration and coating processes, based on accurate predictive information from high-fidelity process models.

Maximise manufacturing flexibility throughout a drug's lifecycle

One of the key aims of Quality-by-Design (QbD) is to determine a safe design space within which a process can vary (for example, as a result of fluctuations in raw material quality) or be varied (for example, in order to maximise product quality for the given conditions).

High-fidelity predictive modelling is a key technology for defining the design space such that all critical-to-quality attributes are met.

Scale-up with confidence: right-first-time commercial designs

Scale-up is one of the key challenges for the pharmaceutical industry, and is considered by many to be a 'black art'. Model-based techniques are becoming widely adopted to assist in reliable scale-up from laboratory to industrial scale. The performance at production scale can now be accurately predicted using techniques that simultaneously take into account chemical phenomena (for example, reaction or crystallization) validated at small scale, and mixing effects calculated using Computational Fluid Dynamics (CFD) models.

Improve process reliability to ensure that results are reproducible every time
Predictive models can be used to determine optimal operating conditions taking into account the variability of external factors such as raw material quality. Process equipment, operating conditions and operating procedures can be designed to ensure that the process is capable of delivering product of suitable quality for a wide range of variations.

Improve product quality

Model-based techniques allow you to improve product quality in many different ways. For example, high-fidelity models of a crystallization process can be used to determine the process conditions that will limit the crystal growth rate during certain phases of the batch. Limiting the growth rate reduces the amount of solvent inclusion in the product crystals, thereby reducing impurities and enhancing quality.

Optimise recipes for example, to minimise batch time

PSE's gPROMS platform was specifically designed as a modelling tool for optimisation of batch processes. This capability is also available in gCRYSTAL and gSOLIDS. A range of techniques

can be applied to optimise recipes for example, to minimise batch time while maintaining quality. The gPROMS platform's powerful dynamic modelling and optimisation capabilities, coupled with its powerful TASK language for describing operating procedures, are ideally suited to for example:

maximising product yield minimising batch time minimising production of impurities minimising wastage of costly raw materials

subject to process and material constraints.

Quantify risk accurately and use reliability information to guide experimental programmes
One of the key challenges is to use experimental data effectively in process design. PSE's data analysis and parameter estimation tools make it possible to generate accurate model parameter information (for example, reaction kinetic parameters) from experimental data so that process and recipe design can be based on accurate predictive information. The associated parameter uncertainty analysis can be used to determine where further data is required in order to reduce risk. PSE's model-based model-targeted experimentation workflow focuses experimental R&D programmes on generating validated models with quantified uncertainty in their predictions. A key aim is to maximise information from experimentation while minimising cost in terms of the number of experiments needed, the amount of API used, the time required etc.

Provide a deep understanding of manufacturing processes.

Understanding the complex interaction between the underlying physical and chemical phenomena in pharma processes such as reaction and crystallization is key to achieving many of the other benefits outlined above. Not only does high-fidelity modelling provide this understanding in a way that cannot be achieved by any other means, but models themselves provide a means to capture knowledge and transfer it across the organisation.

PSE provides an end-to-end modelling platform that allows pharmaceutical organisations to capture their proprietary IP, and that of their collaborators (e.g. academic institutions, consultants, equipment suppliers etc.), in terms of mathematical models spanning the entire lifecycle of a drug product manufacture and its delivery primary & secondary manufacturing operations, drug delivery systems, pharmacokinetic & pharmacodynamics models.

Move from batch to continuous processing

There are many questions to be answered when moving from batch to continuous processing. High-fidelity predictive modelling plays an essential role in the move from batch to continuous, by providing reliable quantitative information that helps test viability and determine optimal equipment size, operating conditions and other aspects, and minimises the risk. High-fidelity models validated against lab or pilot plant data can be used to test every possible operating eventuality in advance of start-up.

Batch-to-continuous
Modelling provides reliable quantitative information that minimises the risk in moving from batch to continuous production.