Win in the marketplace by improving batch quality through employing emerging automation and control technologies
For most pharmaceutical manufacturers, introducing a drug to market is a race against time. There is a threat of expiring patents and constant pressure to consistently meet stringent federal manufacturing regulations. Because of this, major modern drug makers need the competitive advantage offered by pairing sound manufacturing processes with cutting edge and fully integrated control and information systems on the production line.
The Food and Drug Administration (FDA) is advising drug makers to invest in technology to reduce human error and increase drug purity. This fact is underscored in the agency'S compliance guide, "Process Validation Requirements for Drug Products and Active Pharmaceutical Ingredients Subject to Pre-Market Approval." The publication expects manufacturers to have accumulated enough data and knowledge about the commercial production process to support post-approval product distribution. This provides the detailed records essential for expedited pre-market approval and ultimately, a faster time to the finish line.
The best way to do that, the FDA says, is by employing advanced pharmaceutical science and engineering principles, as well as emerging automation and control technologies, to provide a high assurance of batch quality. Information automatically captured by computerized production systems can drive real-time quality assurance to not only speed the drug-to-market time, but to also help drug makers fine-tune their manufacturing processes and maximize efficiency.
Clearly, the most efficient control and information systems are fully integrated, rather than those that include a segmented conglomeration of hardware and software. Even worse is collecting data by hand, which requires tedious visual record reviews. The bottom line: You need the most modern methods to win the race. That way, you protect three key things-your product, your profits, and your reputation.
The Process Validation Life Cycle
For manufacturers that have to rigorously document their operations, the FDA highly recommends following the process-validation life cycle, which can be viewed as a process with four core steps: design, confirm, monitor, and assess. Every step of the way, the key to success is advanced automation technology. Together, the life cycle and a fully integrated control and information system can provide manufacturers with the real-time information needed to help identify and control quality deficiencies. The documentation these tools provide also can help drug manufacturers clear the highest hurdle: FDA approval. Following FDA guidance, manufacturers can use these tools to constantly enhance their processes, operations, and product quality.
Step one in the process is design. Different production lines require different process and control parameters, depending on the drug. Ingredients vary, as do temperatures and packaging. Labels are almost always different depending on the drug. So on the production line, hardware and software must be designed to carefully control and monitor these requirements and associated operating parameters. There are certain standards that manufacturing control systems must meet to satisfy federal regulators and stay on the fast track to validation.
When designing system architecture, drug makers must ensure their equipment is properly installed to operate consistently and reliably. They also must incorporate programs within their process that have the ability to relay critical operating data and information, such as when a batch temperature is too high or a line is down, to technicians, engineers, and executives. This can streamline such processes as risk assessment and troubleshooting.
Another point manufacturers should consider when designing their system is selecting automated equipment that is compliant with ISA-88 standards, meaning the equipment can separate its performance operating information from batch-related parameter information. That way, through the use of various manufacturing software applications, drug makers can monitor the effectiveness of their equipment and attribute each piece of equipment to steps in a recipe. In worst-case scenarios, such as batch deviation, manufacturers can quickly identify the source of the problem, reconcile differences, and replace or modify equipment if needed.
Manufacturers can also gather and utilize the data from other software applications in the production process and work through a manufacturing execution system (MES). This gives them the ability to instantly archive and distribute essential information about the manufacturing process to anyone who needs it in the plant. Accurate real-time communication is only possible through the integration of the information layer and an information-enabled control system.
By building sound manufacturing practices into the drug development process and leveraging fully integrated control and information systems, manufacturers have the power to achieve highly enhanced performance.
Many drug manufacturers have a variety of equipment that gathers data in different computer languages, such as binary or XML. Regardless of the format, today'S advanced control and MES can interpret and disseminate the information to people across the plant floor and on up to business-level systems through integration with an enterprise resource planning (ERP) system. Historical data provided by an MES also can help engineers regularly monitor how well their production machinery is working.
When tightly integrated with an information-enabled control platform, batch management software allows manufacturers to quickly and easily adjust their batch recipes through access to batch consistency data and recipe phases completed during each batch run. Because the information is pinpoint accurate, it allows manufacturers to evaluate and remedy any problems at hand. When used in conjunction with process validation activities, this can dramatically reduce the length and cost of validation time.
To protect consumers, each drug batch should meet the same consistent quality specifications. Batch management software is a vital resource in this process because it captures and records data that can be used to prove the batch process meets quality standards and specifications.
Additionally, this type of software application generally includes a "batch journal," a feature that uses data captured by controllers to log and archive raw materials that go into the making of each drug. Easily accessed by authorized individuals, engineering or quality personnel can look at data collected at a certain date or time to determine weak links in production processes. This tool can help lower risk of "out-of-spec" products and the possibility of equipment failure.
Monitor Real-time Performance
Each piece of equipment has an effect on processing the end product, so each needs to work at peak performance. Many manufacturers employ real-time performance management software to quickly reveal any variation in the process caused by glitches in the machinery. Performance and assess management software enables workers to see the materials, machinery, and time dedicated to each batch.
If operators detect a problem, they can quickly address it by simply reviewing the computer-based information. Operator-interface terminals provide drug makers with a portal into their processes. Machine-specific terminals allow operators to view real-time trend charts and statistical process control graphs related to production data, while scalable, "supervisory" terminals enable designated operators to access information from any aspect of production. Because of the information-sharing capabilities of MES, operators are provided with the data needed to ensure processes run smoothly and key business decision makers get the information they need for order scheduling and resource management.
That'S precisely what Sanofi-aventis hoped to achieve by implementing an advanced information-and-control system at its Ambarés, France production facility. A disconnected and manually intensive tank cleaning process on its injectable liquid production line was inefficient and presented higher risks due to the potential for human error.
The company began investigating ways to improve the efficiency of its existing processing methods. It also sought to achieve compliance with U.S. and European pharmaceutical regulations through 2012; specifically, it began tracking and controlling its water-for-injection loop process in compliance with 21 CFR Part 11 regulations.
To meet its compliance goals, Sanofiaventis implemented an integrated information and control platform from Rockwell Automation. The system tracks data for regulatory and quality purposes, while redundant human-machine interfaces and data servers help ensure continuous process monitoring-even during server failure. An electronic signature feature provides access control and helps prevent unauthorized system changes, such as modifying the setup of key parameters for quality, cleaning, and sterilization.
Information on the strength, quality, purity, and potency of the product can be automatically captured and archived using the advanced technology. It can then be utilized as needed for procedural changes, thus saving drug makers valuable time and money.
Reliable data collection and complete traceability of all sterilization processes has helped the company cost-effectively meet its regulatory compliance demands. Moreover, the complete automated process has helped boost productivity by eliminating non-value add tasks traditionally performed manually, allowing employees to concentrate on core aspects of the business.
The high-tech tools that help drug makers validate processes also can enable them to manufacture their products most effectively. The FDA'S latest validation requirements place a strong emphasis on post-production assessment to help manufacturers continually refine and improve their processes. In addition to getting real-time feedback, drug makers can set regular periodic data-gathering cycles on, for example, a monthly or quarterly basis to monitor the success of any changes. The information provided through an MES also can help in making smart choices when it comes to key business decisions regarding personnel requirements, scheduling production, ordering materials, releasing batches, or maintaining equipment.
Finally, this advanced approach makes it easier for manufacturers to change any procedure in accordance with their own change control program, no matter how small, and without affecting the validation of the entire process. The FDA mandates that drug makers document any procedural changes in a post-market report. Information on the strength, quality, purity, and potency of the product can be automatically captured and archived using the advanced technology. It can then be utilized as needed for procedural changes, thus saving drug makers valuable time and money.
Without accurate information, drug manufacturers may fall short of the finish line in the race to market. By building sound manufacturing practices into the drug-development process and leveraging fully integrated control and information systems, manufacturers have the power to achieve highly enhanced performance and competitive advantage. �
Kovacs is the senior industry technical consultant and deSpautz is the business development manager, Asia Pacific, at Rockwell Automation Life Sciences. Reach