 
 Email
for more information
Company's
other products
Email
to a colleague
Printer
friendly format
|
|
Automation - The Key To S88 Certification
How Merck Sharp & Dohme Met ANSI-ISA S88 Requirements and Improved Batch Control and Flexibility
At one time, in order to be successful, the only option for drug manufacturers was to produce nearly identical products for all markets as quickly as possible. However, developments during the last two decades, have led to a dramatic change in industry requirements. Today, companies must be able to constantly satisfy market demand for new products, even if they involve only slight changes to existing recipes. As if this were not enough, manufacturers receive suggestions for product improvements from the industry's R&D laboratories on a daily basis.
In addition to internal forces, the “push” model of a pharmaceutical manufacturer’s production cycle is being increasingly challenged by the “pull” approach, reflecting the actual demand situation. The average lifespan of a drug is currently between 2 and 3 years, but once a package has reached the last 8 months of its shelf life, the manufacturers can no longer sell it.
The pharmaceutical industry — already confronted with an array of international regulations — is thus expected to become ever more flexible yet keep up with production demands. This situation leads to an increase in competition even among the subsidiaries of the same group that must constantly prove their ability to keep up and justify their investments.
Under these competing market conditions, automation becomes fundamental, paving the way for companies to adapt outdated plants to current requirements without the need for substantial investments.
Under The Sign Of S88
The ability to use programs based on the ANSI-ISA S88.01 automation standard is extremely important in the pharmaceutical industry. This international standard describes common models and concepts, which can be used to define the requirements for batch control. Meeting the requirements of S88 enables manufacturers to manage the production of individual quantities of composite drugs (batches), starting with predefined quantities of raw materials and using a modular scheme of cycles that can be regrouped to obtain different results. The recommendations laid down in the standard also aim at improving control of existing batch production plants and can be applied universally, regardless of a plant's degree of automation.
While operating within international standards, and also trying to meet ever-changing market demands, Merck Sharp & Dohme chose to move forward with the renewal of its tablet compression plant in Pavia near Milan, Italy, with the business intent of strengthening its position as a market leader — a position it proudly held for more than a century.
A conversion such as this is a delicate task. Under today's market conditions, closing a plant for renewal is not an option. Production must continue, even if it means operating the plant on weekends and holidays.
During the renewal of the MSD plant, new components were added in succession. The sequence was planned to ensure optimal time for inspection and approval by Italian and European regulatory bodies and FDA specialists, and to guarantee maximum protection of the patients' health and safety. For this project, a team of specialists was set up and entrusted with the task of optimizing the automated control of each operation in the manufacturing process.
Facing this daunting task, Maurizio Mangiarotti, of Merck Sharp & Dohme, selected Rockwell Automation, a leader in developing technologies and providing services that leading manufacturers around the world use to their competitive advantage.
Among The Leaders In Europe
“While the old facility for fluidized bed granulation ensured optimum quality of the finished tablets,” explains Mangiarotti, “there were many smaller problems which had considerable impact on the productivity of our control system.” The first step was to review the electromechanical system. The goal was to replace the operation mode so that line personnel with PLC-based next-generation control systems could exploit the processing potential to the fullest. Ultimately, Merck decided to employ an SLC 5 system by Rockwell Automation, along with the company’s ControlLogix platform and RSView SE monitoring software.
Adapting the SE-based software to enable communication with the internal system currently in use at Merck turned out to be the most delicate part of the operation. In a joint effort, engineers from the two companies found a solution which delivered high performance and fulfilled control requirements .
Once this initial modification was completed, ControlLogix took over responsibility for all steps in tablet production — from the dispensing of the solution by retrieving the single components from their storage locations, through to final tablet compression, including mixing and thermal treatment of active and auxiliary substances.
With the automation of all of these production steps, the first project phase was considered a great success. Mangiarotti said he intends to automate the deployment of recipes in the near future, creating an entirely automated facility configuration. He said this could not happen without a software solution such as RSView — a software product which guarantees a high degree of flexibility and meets the current and future demands of a modern pharmaceutical plant.
By using innovative electronic-based solutions, Merck has managed to be one of the first companies in Italy to comply with the S88 standard, making the Pavia site a leader among European plants.
Next-Generation Technology: From The Switchboard To A Single Click
Production control with the previous 20-year old system involved a high degree of manual involvement. For each operation, production engineers were required to select the right button from a vast switchboard; cycle times and physical values were then monitored on the appropriate instruments. Apart from dramatically limiting the plant's efficiency, this process required verification steps, taken to avoid the production of tablets that deviate from the defined composition. Today, all process steps are thoroughly analyzed and defined in advance. Once a new product has been defined and selected for production, all of the manufacturing steps are carried out automatically, eliminating the risk of human error. An alarm system only notifies the personnel in charge in the event of irregularities, it also displays trends for every single value allowing for preventive maintenance, an essential prerequisite for avoiding unexpected production downtimes.
Automation has also revolutionized production logic. With the former MSD system, production was limited to manufacturing a single product at a time. Once the level of necessary raw materials had been identified, the facility was reserved for creation of this particular product only. Switching to a different recipe, even if there were only slight changes to a component dosage, was only possible after the termination of the current batch. Each product change also involved long changeover times. For a modern manufacturing plant requiring a high degree of flexibility, such conditions are unacceptable.
Thanks to the renewal, the Merck plant was able to attain a high degree of flexibility. Today, the facility allows completion of the tablet compression for one batch at one end of the line, while at the same time initiating the mixing cycle for an entirely different product. Parallel processing of different recipes helps companies continuously reduce their batch sizes, representing a dramatic change in pharmaceutical production methods.
Until recently, the plant needed a daily production output of at least three million tablets in order to work profitably — with the resulting consequences for storage and distribution. Thanks to extraordinary manufacturing flexibility, new automation systems offer the potential for production of one billion tablets per year and even allow multiple format changes on a single day. In many cases, the only limit being a thorough cleaning between two batches.
Benefits Beyond Production
The productivity gains experienced by Merck can also be attributed to the fact that all processes underwent a strict standardization. “The PLC needs precise and clearly defined parameters to manage every single operation,” said Mangiarotti. A case in point for such an increase in productivity is the issue of temperature control of the desiccation system. The pharmaceutical industry is required to adhere to a very narrow tolerance range. To ensure perfect desiccation, the conditions in the dry heat oven must be verified at regular intervals. The actual duration of the desiccation process cannot vary as a result of external factors. In the case of the MSD project, one rainy day was sufficient enough to delay the drying process, causing disturbances further down the production and distribution chain. Today, the automated control system allows all parameters to be managed remotely, based on variable values being measured at relevant points throughout the line, and optimization of cycle times. Furthermore, automation proved to be a fundamental tool for the efficient management of batch documentation — information that pharmaceutical manufactures are required to maintain to remain in compliance with international legislation. The ability to retrieve process data rapidly and directly, on the line guarantees perfect traceability of the entire production cycle — at a level of detail that, in the case of Merck, even exceeds the especially strict FDA regulations.
Everything Under Control
In any number of other industries, restructuring is relatively easy. However, such actions require validation by public authorities if they affect the production of pharmaceuticals. For this reason, a gradual renewal at Merck included thorough analysis and preparation to ensure that the actual installation would be done quickly, without requiring readjustments at a later stage. Avoiding corrections was vital to the project. International regulations for pharmaceutical production are especially strict and allow no tolerance for variation. Mangiarotti’s team relied on Rockwell Automation to obtain all necessary certifications as quickly as possible. “This is not only about great names,” emphasizes Stefano Battiglia, Director of Automation & IT Operational Excellence at Merck. “We needed a solution we could trust entirely.”
Among the Rockwell Automation portfolio of products, ControlLogix was identified as the best control platform for the process. This PLC allows for a matrix-based system along with all the benefits it offers to batch production. “To tap the full potential,” Mangiarotti recounts, “we needed to establish a special work group so that our internal experts were supported by specialists from Rockwell Automation. Thanks to their help, we were able to achieve a level of performance that exceeded all expectations. At the same time, all S88 standard regulations were adhered to in detail.”
There was no doubt when it came to selecting the appropriate control platforms and network technology to be installed. Two different systems were to be evaluated: ControlNet and DeviceNet. The latter is especially suited for networking highly diverse devices, and also requires the use of intelligent components at network level. At Merck, however, the facility provides for a conventional analogue and digital I/O solution. The functionality of ControlNet proved to be ideal for this infrastructure.
At the super ordinate protocol layer, in contrast, Merck decided in favour of Ethernet. This protocol allows for the networking of multiple PanelView modules as well as the connection of PCs and servers, used for subsequent traceability and connection to the office world. To minimize the risk of external attacks on the production network, a dedicated firewall was set up to separate Production IT from the administrative network.
“Though current control systems increasingly aim at full facility automation,” Battiglia explains, “they have no direct effects on the quality of the finished products. Monitoring of pharmaceutical manufacturers has already set the standard in this respect. However, the renewal of our production site has given us the opportunity to shorten our throughput times by optimizing some of our processes so we can better react to the demands of the market.”
The increased level of productivity and the ability to produce only those batches that are actually needed make room for flexibility that is crucial for further investment in research and development. Ultimately, this is the only way to develop new and effective drugs to protect the most important commodity ever — our health.
Pharmaceutical Processing
Advantage Business Media
|
