The goal of the US Food and Drug Administration's process analytical technology (PAT) initiative is to encourage pharmaceutical manufacturers to improve their operations to reduce the cost of pharmaceuticals. Before the PAT initiative, there was not much emphasis on changing ongoing pharmaceutical operations—repeatability, not innovation, was the order of the day.

Now that the regulatory climate has changed, how can pharmaceutical manufacturers look to achieve results? Today's automation systems can be an excellent place to begin. Technology is now available to automatically evaluate measurement and control performance and point directly to those areas where improvements are possible. Reduction in process variability is one of the key areas that can be influenced by this effort. Imagine the impact on costs if production cycle times can be reduced or a few rejected, out-of-specification lots of material can be avoided by improving operations to ensure that all manufactured goods are made right the first time.

PAT initiative brings changes

The pharmaceutical industry often has been reluctant to introduce change into their manufacturing processes because of perceived regulatory complications. From a manufacturer's perspective, the regulatory process has been rigid and unfavorable to the introduction of innovation. Process changes are managed by time-consuming regulatory submission. Thus, many manufacturing procedures traditionally were treated as being unchangeable.

Realizing the impact this has on manufacturing efficiency and innovation, FDA established the PAT initiative to encourage the voluntary development and implementation of innovative pharmaceutical development, manufacturing, and quality assurance. As part of this framework, an innovative approach has been developed for helping the pharmaceutical industry address regulatory issues and questions. This new approach is discussed in A Guidance for Industry, PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance. The agency's usual regulatory scrutiny has been tailored to meet the needs of PAT-based innovations that promote continuous improvement and improve manufacturing while maintaining or improving the current level of product quality.

The primary goal of PAT is to enhance understanding and control the manufacturing process to ensure final product quality. The concepts addressed by PAT are applicable to all manufacturing situations. Nonetheless, the gains in quality, safety, and efficiency will vary depending on the process. In general, these gains are anticipated to come from:

• reducing production cycle times by using measurements and control;
• preventing rejects, scrap, and reprocessing;
• improving operator safety and reducing human error;
• improving efficiency and managing variability.

There are many current and new automation tools that can effectively facilitate process understanding and achieve continuous improvement. The PAT framework defines the following tool categories:

• multivariate data acquisition and analysis tools;
• modern process analyzers and process analytical chemistry tools;
• process and endpoint monitoring and control tools;
• continuous improvement and knowledge management tools.

As defined in the PAT framework, an appropriate combination of some or all of these tools may be applicable to a single unit operation or to an entire manufacturing process and its quality assurance. The challenge for many manufacturers is to identify how best to address the opportunities that PAT offers. This article focuses on the first steps that may be taken to improve operation through process monitoring and control tools. Often these tools are available in your existing automation system or may be easily added to the system.

The control challenge

Conventional pharmaceutical manufacturing is generally accomplished using batch processes with laboratory testing conducted on collected samples to evaluate quality. Also, most pharmaceutical processes are based on time-defined end points. The role of the automation control system is to control all critical quality attributes to insure consistent quality of the end product. Thus, as outlined in the PAT framework, process controls play an important part in the design of the manufacturing process and in the validation process. In such batch applications, however, the control system itself may face many challenges that affect how closely the control parameters may be maintained and how quickly the control system can respond to process changes throughout the batch cycle.