Life Science Industry Manufacturing Challenges: How Integrated Control and Information Helps OEMs Prosper in a Competitive, Regulated Environment This white paper takes an in-depth look at challenges facing life sciences companies and their suppliers in an environment of changing regulations and increased barriers to entry. It shows how the Rockwell Automation approach to control and information can help OEMs produce prevalidated machines, reduce time-to-market, reduce validation costs, enhance product differentiation and protect intellectual designs. 1
INDUSTRY OVERVIEW The outlook for life science manufacturers is challenging. In the next five years at least 20 blockbuster products with combined sales of nearly $40 billion will lose patent protection. Meanwhile, waiting in the wings are generic drug manufacturers who are getting smarter at introducing products closer to the patent end date taking the risk that the brand name manufacturer will not get a patent extension. Add to this the rising costs of compliance and increasing barriers to market entry and it is easy to see why both brand name and generic life sciences companies are realizing that manufacturing optimization is not just a lofty, long-term goal -- it s an immediate necessity. The last decade has proven that agility and efficiency are required skills to grow in this extremely competitive and highly regulated environment. Companies must invest heavily in R&D to fill the product development pipelines with evermore complex drugs. They must meet continuously shifting and increasingly demanding U.S. Food and Drug Administration (FDA) regulations, and in this environment of constant change, they must quickly adapt and accelerate the production process to maximize the ROI of the entire drug s life cycle. It is currently estimated to cost a manufacturer around $800 Million to get a new drug to market, including between $80-140k for validation. And this cost is set to rise given more complex diseases yielding more complex antidotes, manufactured with more complex technology. Additionally, the FDA is implementing a more cautious review process and demanding a greater number of complex clinical trials, which in turn increase the time to market. These demands are met by manufacturers implementing enterprise-wide, integrated control systems, which enable them to achieve regulatory compliance, minimize recurring costs of compliance and reduce time-to-market without sacrificing product quality. Manufacturers are expecting OEMs to deliver cost-effective machinery that provides more information and integrates efficiently with compliant architected systems. 2
This white paper takes a look at challenges for OEMs serving the life sciences industries and examines how Rockwell Automation solutions can help OEMs meet these challenges. Achieve Compliance and Improve Documentation To enhance manufacturing efficiency and minimize validation and compliance costs, automation systems must be capable of addressing three key architectural and regulatory standards: 21 CFR Part 11 deals with the generation and integrity of electronic records and electronic signatures (ERES) in manufacturing operations; ANSI ISA S88.01 identifies common models and terminology for batch-control systems; and GAMP 4 addresses the documentation necessary for verification of compliance. 21 CFR Part 11: Regulating ERES systems The FDA ruling, 21 CFR Part 11, provides the policy for compliance of all regulated ERES systems in the pharmaceutical, biotechnology, medical products, cosmetics, food and fine chemicals industries. 21 CFR Part 11 was made law in 1997. It states that manufacturers using ERES must prove that systems can effectively store, process and transmit electronic records and associated signatures without fail. System validation also is a key requirement of 21 CFR Part 11. To help ensure ongoing compliance with this directive, manufacturers in regulated industries are responsible for working closely with the FDA and equipment and service suppliers to efficiently and economically integrate into their operations compliant electronic equipment that handles electronic records and electronic signature (ERES) systems. Manufacturers need to analyze the potential benefits of implementing electronic versus paper records. Where the risk of a change in the recipe mix yielding an unanticipated impact on the consumer is high, the benefit of repeatable quality far outweighs the financial investment required to implement ERES. As well as removing the risk of human error, an electronic system makes it easier to share, store, retrieve and analyze information in ways not possible with paper records, and improve the quality and security of documentation. The agency is 3
making continual changes to the scope and application of requirements for validation, audit trails, record retention, record copying and legacy systems. Only time will tell what the regulations will look like in the future, but manufacturers who are headed down the electronic documentation path shouldn t view the FDA s re-engineering as a reason to halt the process. While the anticipation of new regulations is certainly a reason for reviewing electronic documentation systems, even more important is recognizing the significant ROI benefits over traditional paper-based methods. ANSI ISA S88.01: Good Manufacturing Practices for operations ANSI ISA S88.01 (S88) outlines standard models and terminologies that define good manufacturing designs for implementing and running a manufacturing operation. The structure of batch-type production must be tightly linked to a control system and consist of two main components: the physical components of the plant and the operating processes. Specifically, S88 provides standardized definitions and properties for batch process objects, physical objects, batch control objects, recipes and recipe components. These models and terminology help emphasize sound procedures for the implementation and operation of a batch-type manufacturing plant, and boost operational speed and agility. GAMP: Meeting validation requirements The Good Automated Manufacturing Practice (GAMP) Forum was created to promote an understanding of the regulations affecting life sciences companies. A series of GAMP guides, developed by the GAMP Forum, are designed to help pharmaceutical companies and their suppliers reduce the cost and time required to achieve compliant systems. The GAMP Forum methodology identifies the qualification and testing measures required for validation, as it relates to design, installation, operation and performance of the system (IQ, OQ & PQ). 4
OEM OPPORTUNITIES Today, OEMs and end users realize that producing and maintaining FDA-mandated audit trails, electronic records and copies, time stamping, and validation puts more emphasis on the need to access information from machines, whether electronic or paper record based. Pharmaceutical manufacturers and equipment suppliers now understand that there is no silver bullet for compliance and that those who delay will only fall further behind the curve. To address this issue manufacturers are combining FDA compliance needs, regulatory guidelines, OEE, SCADA, storage/archive systems, recipe management systems, etc. into a single specification set to determine their automation standards for future manufacturing. This in turn will force OEM s to reevaluate their offerings to include variations of any one machine based on the different specification sets. Lower Validation Costs Process validation is defined by the FDA as establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. In other words, companies must be able to prove they are producing a safe, consistent product. Recent studies have shown that the total cost of compliance for medium-to-large drug manufacturing facilities can reach as high as 25 percent of the total operating budget and 80 percent of the cost of implementing a control system, excluding raw materials. Furthermore, manual sampling is a time consuming process that significantly delays releasing product to the market. The focus of manufacturers and OEM s alike has to be to develop quality management into the control system to reduce the need for manual sampling yet still allow for validation. FDA delays and citations due to manufacturing validation deficiencies have resulted in losses at more than a million dollars a day for a single drug. Lack of adequate changeover capabilities can be a major roadblock in maintaining an efficient validation process. Pharmaceutical manufacturers must complete an FDA validation audit every time they produce a drug. To efficiently change over from one product line to the next, 5
manufacturers need well-developed validation methods and agile, robust machines that can support multiple product recipes. Systems that lack modularity or plant-wide integration are more time-consuming for the FDA to review, and inspectors have a difficult time identifying if good manufacturing practices were used. By implementing control and information architectures on their machines, OEMs can help their life sciences customers reduce validation time and costs by automating the acquisition, storage and retrieval of all manufacturing data. Architectures can also help protect the integrity of system information required for certification with advanced batch control and reporting capabilities. As the FDA begins to enforce best practices, pharmaceutical companies that want to streamline regulatory compliance and reduce validation costs will move towards more standardized technology across their operations. Reduce Time-to-Market Both generic and brand name manufacturers are facing pressure to introduce new products faster, while containing costs and reducing risks. Pharmaceutical companies are often put in the difficult position of trying to balance competing forces such as the need to achieve regulatory compliance and reduce validation costs while reducing the time it takes for new drugs to reach consumers. On average, it costs $800 million and takes nearly 14 years for a brand name manufacturer to take one drug from research and development to final delivery. Patent protection for marketing and amortization typically expire in 8 years, so the day clinical trials are complete should be the day manufacturing begins in order to recoup development costs. Time-tovalidation and production ramp-up time must be minimized even as manufacturers are using more complex systems and diagnostic data to maximize revenue potential and product margins before patents expire and competition from generics begins. 6
Optimizing Production Once production begins, both generic and brand name companies demand speed and accuracy from equipment to maximize manufacturing efficiency. For OEMs, the challenge is to design a machine that will reduce downtime and easily integrate into the entire manufacturing process. Manufacturers need OEMs that can improve agility and ease changeovers by providing standardized systems that allow functional, repeatable control. Off-the-shelf systems that eliminate paperwork and reduce errors, while maintaining expected high quality standards, help improve plant throughput and will reduce the time it takes for compounds to reach consumers. At the same time though, the need to protect machine designs, offer differentiated machines, reduce the cost of machine compliancy and deliver machines faster remains uppermost in the OEM s mind. Conclusion Achieving regulatory compliance, improving documentation, lowering validation costs and reducing time-to-validation are necessities for pharmaceutical manufacturers to survive in today s changing market. Life sciences manufacturers are depending on OEMs to accelerate production capabilities and provide machines that are a proactive part of manufacturing optimization, while maintaining repeatable quality. There is growing pressure on OEMs to deliver the right machine for the job today while remaining flexible enough to meet the future specification sets of their customers. Additionally OEMs need to be far sighted in judging how processes will merge in the future (for example packaging substances from the freeze/dry application direct into blister packs) and be prepared to face these new challenges as they arise. 7
THE ROCKWELL AUTOMATION SOLUTION In a recent Rockwell Automation survey, OEMs serving the pharmaceutical market named improving documentation and achieving 21 CFR Part 11 compliance as the key needs of the industry. It can be confusing and time-intensive for OEMs to stay abreast of validation and regulation requirements, while reducing the cost of implementing control systems to provide better information. To meet these demands and minimize the strain on their own internal resources OEMs can leverage the expertise of their automation partners. With a customer base that includes 95 percent of the Fortune 50 pharmaceutical companies, Rockwell Automation has an extensive history in the regulated industries. By drawing from this experience, Rockwell Automation is able to develop products that deliver maximum value, feature well-defined functionality, and are designed to help customers meet FDA and industry regulations. Integrated Architecture Rockwell Automation takes a holistic, system-wide approach to manufacturing optimization. Integrated Architecture which includes control, integrated motion, visualization and networking technology focuses on the entire application and its relationship to other plantfloor activities. This gives life sciences companies a solution they can easily incorporate enterprise-wide and OEM s a scalable solution that integrates well into their customers plant. At the heart of the architecture is a flexible, modular and open control platform with inherent built-in security features to make validation adherence a more simple process. From formulation to factory production, this control platform helps OEMs meet their customer s regulatory compliance and integration needs. It also provides the foundation for an OEM to provide a range of differentiated machines based on their customers specification sets, while optimizing efficiencies of scale. 8
Control Platform with Common Engine The Rockwell Automation Integrated Architecture uses the Logix platform for horizontal integration across sequential, motion, process and drive control. Manufacturers need only one type of control across multiple applications, such as batch process and packaging. All Logix controllers, such as the high performance, multi-discipline ControlLogix platform, also use a common control engine. By tying all control functionality into a single, multi-tasking platform, Rockwell Automation Integrated Architecture eliminates the complexity, information synchronization and program development problems common with systems using independent controllers. With Logix controllers, OEMs can use the simplified control and visualization program design, integrated sequential, process and motion control functionality, and reduced number of hardware components to lower machine cost and time to market, while still allowing them to protect their design. Additionally, ControlLogix enables an OEM to set up security levels managed by RSMACC (Rockwell Software Maintenance Automation Control Center) software, which detects and records altered electronic records. When ControlLogix is under the auspices of RSMACC, an operator is not able to change parameters on the machine unless he has the correct authorization level. This built-in security feature helps maintain the integrity of the compliant system. OEMs can select the appropriate Logix controller based on a variety of requirements, including number of I/O, memory-size and physical footprint of the platform. Single, Scalable Programming Environment Common development tools allow engineers to reuse programming resources, which can help eliminate repetitive tasks and minimize design efforts. All controllers leveraging the Logix control platform are configured using Rockwell Software RSLogix 5000 software, which dramatically reduces programming time. RSLogix 5000 eliminates the need to purchase and maintain separate motion, sequential and drives programming tools. The software features flexible, easy-to-use editors, a common look and feel, superior diagnostics and 9
troubleshooting tools, and powerful functionality. Using a tag-based addressing structure, Logix code is easily edited and reused in similar processes, helping to further reduce engineering costs. Within this programming environment, Rockwell Automation has established key frameworks that help drive design efficiencies in engineering. The use of state models, object-oriented programming and tag-based functions all play a vital role to utilize best practices and establish a engineering blueprint for machine design to help reduce development time and cost. They also serve to provide consistency on how a machine operates by improving service improves, reduce training and increasing uptime. Multi-user Design Environment RSAutomationDesktop is a multi-user design environment that facilitates the design of modular machines. The value of RSAutomationDesktop becomes increasingly obvious to large multiteam, multi-location OEMs. It provides a common IT environment to set up the structure for deployment of best practices and reusable code. It also helps teams manage the engineering process and provides management of software licenses, etc. Another significant value is its ability to handle a multitude of disparate types of documents and content which are usually associated with machines. FactoryTalk technology is embedded to check and manage tag names and usage. Modular, Integrated Recipe Management Integrated recipe control reduces changeover time. Pharmaceutical companies can eliminate the repetitive process of tuning equipment during a line change by saving and managing multiple settings. By integrating this capability into their machine design, OEMs can help increase the agility of operations for pharmaceutical manufacturers, as the switch between drugs no longer requires a complete engineering redesign. 10
Integrated Architecture lets companies manage recipes within the Logix platform using either RSView or RSBizWare Batch software. Using RSBizWare Batch software, operators can create, store and automatically sequence recipes as designed. The system will initiate various control commands to carry out the recipe and report the result of each command. The data is then merged with an alarm and activity log to create a complete batch record. With this record, operators can analyze batch-to-batch performance, study trends and formulate processoptimization strategies. Batch process management allows for the reuse of code, recipes, phases and logic between processes with comparable procedures, which reduces programming and set-up time for OEMs. Common HMI Platform A window into the machine operation is often an important customer requirement, but the choice of whether to use either a dedicated operator interface or open industrial computer can leave an OEM facing the prospect of developing multiple visualization programs depending on the platform, with little or no reuse, and having to validate each solution. Rockwell Automation developed its ViewAnyWare strategy the visualization component of Integrated Architecture to deliver a unified and scalable suite of HMI solutions. This provides significant cost reduction and reduced HMI screen development time, along with the ability to reuse applications across different sizes of machines. In addition, RSView Enterprise Series is FactoryTalk-enabled, allowing users to collect, store and examine system activity (such as RSView Supervisory Edition, RSView Machine Edition or RSLogix activities) in one centralized location. This reduces the time to integrate control and visualization on a machine and significantly simplifies the documenting process for users complying with cgmp regulations. Networking Services Seamless communication from mainframe computers to plant floor devices is possible using NetLinx, the open networking strategy for Integrated Architecture. Using NetLinx, OEMs can 11
provide their customers with systems that can communicate over any network based on the Common Industrial Protocol (CIP), including EtherNet/IP, ControlNet and DeviceNet networks. With the ability to gather, analyze and archive information from the plant floor to the boardroom, pharmaceutical companies can dramatically reduce quarantine time required for validation and accelerate time-to-market. For example, electronic batch reports can reduce quarantine time by reducing the batch review cycle time. The goal of connecting every piece of equipment across a processing facility (horizontal integration) is to ensure the plant is not comprised of isolated cells of activity. It gives departments the ability to access plant-wide data and quickly adjust to change. Information must also be able to flow in real-time from the plant floor to business-level systems (vertical integration) in order to increase productivity. With networked machines, OEMs can conduct full tests at their production facilities and then break the machine down into sections for shipping. This allows the machines to be implemented more quickly and gives OEMs the confidence the machine will run smoothly when reassembled. Information Sharing Through Manufacturing Execution Systems (MES) In today s regulatory environment, transparent information flow and efficient production management are legally mandated necessities. Through its acquisition of Propack Data, Rockwell Automation can leverage the expertise of the leading provider of manufacturing execution systems (MES) in regulated industries. The Propack Data enterprise production management software allows OEMs to design equipment so data can easily be extracted from the machine. This enables data collaboration and gives end users the capability to bridge the gap between enterprise resources planning (ERP) systems and the plant floor. The integrated platform of Rockwell Automation control helps speed individual applications and makes it easier to share information between the plant floor and business systems without unnecessary data manipulation. With integrated control and advanced information sharing capabilities, engineers, plant management, business and manufacturing system operators all have the means to access and share data both horizontally and vertically throughout their 12
facility. This information can be synthesized into process improvements and is the basis of all data necessary for proof of regulatory compliance. Simplified Regulatory Compliance The maze of ever-changing regulations can be confusing and time-intensive for OEMs who need to stay informed of compliance mandates. OEMs can rely on Rockwell Automation services and products to reduce the regulation learning curve and cost of compliance. By leveraging these technologies to streamline compliance, OEMs can improve the value of their machines and differentiate themselves in the competitive market. The Rockwell Automation Integrated Architecture is designed to work with several pharmaceutical-specific standards to enhance and facilitate compliance. For example, RSMACC detects and records altered electronic files, which is required by various industry regulations, including 21 CFR Part 11. The change management system automatically tracks changes made to Logix controller programs and provides a centralized repository for auditing plant-wide maintenance information associated with change management and asset health. The architecture also adheres to the requirements of ISA S88.01. With Integrated Architecture, OEMs can make control changes on a modular level, rather than system-wide, which greatly facilitates system optimization. The resulting modular documentation needed for validation becomes much simpler to manage. OEMs also can help customers lower validation costs and reduce variability with Rockwell Software solutions. For example, RSBizWare eprocedure helps OEMs automate manual procedures using an interactive, Web-based interface to sequence and document manufacturing operations. eprocedure provides the consistency of automated controls in manual operations, executes recipe instruction, controls the resources of the process cell, displays instructions to operators and logs all responses. 13
RSBizWare Batch Historian is a complete solution for collecting, analyzing, viewing and reporting data. Batch Historian turns masses of confusing production data into useful information and reduces process variability by analyzing a wide variety of data such as temperature, pressure and flow rate. After Market Support Rockwell Automation offers after-market services and support for life science manufacturers and OEMs to improve operations from R&D through clinical trials and production. The company s Regulatory Compliance Services help life sciences manufacturers address an array of compliance issues, including validating computerized systems and processes, meeting cgmp requirements and managing electronic record keeping. By working with OEMs the Regulatory Compliance Services team can develop formal programs to address audit criteria to help end users comply with FDA regulations. Additionally, Rockwell Automation supports the OEM on customer projects by recommending how to implement their machine into the manufacturer s plant floor environment to comply with 21 CFR Part 11. Finally Rockwell Automation can help in developing the necessary documentation deliverables suitable for the manufacturer s validation efforts. This enables OEMs to help their end users reduce compliance costs and bring products to market faster. Conclusion The Rockwell Automation proven architecture - consisting of hardware, software and services - can help OEMs reduce risk, protect their intellectual property, and differentiate themselves in a changing and competitive market. OEMs must strike the ideal balance between protecting their intellectual property and giving end users enough control to manage equipment. OEMs who rely completely on automation 14
suppliers for control intelligence lose ownership of intellectual property and run the risk of creating generic machines. In contrast, OEMs who supply machines with all custom controls will face increasing challenges as customers demand greater access to and visibility of information. OEMs can retain control over their intellectual property while allowing end users to effectively manage their system with cost-effective, off-the-shelf controls that can be easily integrated into the plant-wide system. Rockwell Automation Integrated Architecture allows OEMs to retain control of code and other intellectual property so they can support relationships with customers and improve modularity of machines. By leveraging Rockwell Automation s leadership in industrial automation, OEMs can help elevate pharmaceutical companies needs to optimize process quality, improve throughput and facilitate regulatory compliance. OEMs can utilize the pharmaceutical experience, batch technology, proven hardware and consulting resources of Rockwell Automation to differentiate themselves and ensure customer satisfaction. 15
www.rockwellautomation.com Corporate Headquarters Rockwell Automation, 777 East Wisconsin Avenue, Suite 1400, Milwaukee, WI, 53202-5302 USA, Tel: (1) 414.212.5200, Fax: (1) 414.212.5201 Headquarters for Allen-Bradley Products, Rockwell Software Products and Global Manufacturing Solutions Americas: Rockwell Automation, 1201 South Second Street, Milwaukee, WI 53204-2496 USA, Tel: (1) 414.382.2000, Fax: (1) 414.382.4444 Europe/Middle East/Africa: Rockwell Automation SA/NV, Vorstlaan/Boulevard du Souverain 36, 1170 Brussels, Belgium, Tel: (32) 2 663 0600, Fax: (32) 2 663 0640 Asia Pacific: Rockwell Automation, 27/F Citicorp Centre, 18 Whitfield Road, Causeway Bay, Hong Kong, Tel: (852) 2887 4788, Fax: (852) 2508 1846 Headquarters for Dodge and Reliance Electric Products Americas: Rockwell Automation, 6040 Ponders Court, Greenville, SC 29615-4617 USA, Tel: (1) 864.297.4800, Fax: (1) 864.281.2433 Europe/Middle East/Africa: Rockwell Automation, Brühlstraße 22, D-74834 Elztal-Dallau, Germany, Tel: (49) 6261 9410, Fax: (49) 6261 17741 Asia Pacific: Rockwell Automation, 55 Newton Road, #11-01/02 Revenue House, Singapore 307987, Tel: (65) 6356-9077, Fax: (65) 6356-9011 Publication LS-WP001A-EN-P January, 2004 Copyright 2002 Rockwell Automation, Inc.. All rights reserved. Printed in USA. 16