Computer system validation ? increasing supplier value 1

By: David James
All sectors of manufacturing are under continual pressure to bring new products to market quicker, stealing a march on the competition and maintaining their revenue stream. Manufacturing industries are also under pressure to reduce the cost of design, production and distribution processes to increase margins and maximize return on investment (ROI). Pharmaceutical manufacturing is no different; competition is fierce, and investors in drug development and manufacturing companies are looking for a healthy return on their money.
However, whereas most manufacturing organizations have seen health and safety regulations tighten over recent years, pharmaceutical manufacturers are also under pressure from the regulatory authorities in the regions where they wish to market their products. The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK and FDA in the US, for example, regulate and monitor pharmaceutical manufacturers from the process plant design stage through to the day-to-day production of active pharmaceutical ingredients (APIs) and finished products. Whereas being first to market is usually a key objective for manufacturing organizations to maximize product returns, pharmaceutical manufacturers have the added pressure of patent lifetimes. If most of the patent duration is used to perform clinical trials and build a manufacturing plant, there is a reduced protection time in which to recoup drug development costs.

Figure 1

These various pressures work against each other as shown in Figure 1. Complying with health and safety, and regulatory requirements inevitably increases costs, whereas shareholders want to see expenditure reduced. Patent protection periods limit the time over which high margins can be obtained so reducing the time-to-market is paramount. It is the nature of control systems for process plants that they become an activity on the critical path of the manufacturing plant development. To complete the configuration of a control system all details of the process, instrumentation and control devices must be finalized. Similarly, to finalise site tests and commission the system, all aspects of the plant, including the installation of the instruments and control devices, must be complete.
Consequently, the time pressures on the control and instrumentation engineer are very high, regardless of the industry. For the pharmaceutical industry, however, we have the additional requirement to conduct the initial stages of computer system validation (CSV) on the control system before performance qualification (PQ) of the whole process control system can be undertaken.

Table 1

When it comes to the site activities associated with those initial stages of CSV, things are not as bad as they appear. Operating companies can significantly reduce the time taken to perform installation qualification (IQ) and operational qualification (OQ) activities, enabling them to both reduce cost and get into production earlier, by capitalizing on the work performed by their control system supplier. Definitions of PQ, IQ and OQ are provided in Table 1. The principles discussed in the rest of this article could be applied to any packaged system, whether it includes controls or not. Therefore, the installation of, for example, a clean-in-place skid or a vacuum package that undergo functional acceptance tests in the factory before delivery could also gain from the proposition that follows.
Obtaining 'buy-in'
Our objective is to minimize site activities associated with validation by reducing IQ tasks wherever possible and only performing OQ activities where they are dependent upon the site environment; for example, where the control system interfaces to another piece of equipment that could not be installed or simulated within the supplier's works.
A prerequisite for this approach to be effective is to involve your site validation staff from the start.