Medical device manufacturers, like manufacturers in other industries, must control costs, ensure product quality and shorten time-to-market. For the life science manufacturing industry, a noncompliant product or process does not simply result in expensive rework or customer dissatisfaction, it can cause illness, disablement, even fatality.
As a result, the U.S. Food and Drug Administration (FDA) requires that life science manufacturers meet stringent quality and manufacturing standards. The industry is guided by quality standards including a new FDA regulation, Regulation 21 CFR Part 820. Like ISO 13485, the International Organization for Standardization's quality assurance model for organizations that produce, install and service medical device products, 21 CFR Part 820 addresses a variety of quality-related areas, as well as design, process validation, personnel certification, manufacturing and labeling. Instead of focusing on quality in the traditional sense of improving yield through proactive process management and mitigating costs, the regulations' initial interpretations focused on the cost of adverse quality.
The underlying premise of today's interpretation of the regulations is to ensure quality or risk management and risk mitigation by defining a management methodology for designing quality into the manufacturing process instead of attempting to build quality into products through inspection. The goal of manufacturers and the FDA is to provide and deliver safe and effective products.
However, FDA compliance historically has been an expensive, albeit necessary, proposition. As the life science industry becomes more competitive, reducing the cost of compliance is as important to success as controlling costs, quality and time-to-market.
A Manufacturing Execution System (MES) helps bridge the gap between regulatory control, operational control and case management. Typically, regulatory affairs are focused on FDA compliance and clinical trials, and manufacturing operations are focused on manufacturing and quality issues. By bringing these groups together, the MES helps life science manufacturers improve manufacturing efficiency and product quality, while at the same time lowering manufacturing costs and developing products that meet FDA regulations.
When the FDA began regulating the life science manufacturing industry, manufacturers were just starting to use electronic systems such as Enterprise Resource Planning (ERP). As a result, FDA regulations specified that manufacturers must maintain records, such as on a paper traveler, that record activities and signature approvals from product conception to completion. Paper travelers are a checklist and sign-off of all major steps in the manufacturing process. The industry is now in the early stages of moving this to an electronic format.
In the short term, paper travelers provided life science manufacturers with a concrete mechanism to track a device's history record. However, after the records were complete, they had to be archived. When a product was recalled or a quality problem arose in the field, the paper system's inadequacies appeared. Manufacturers had to assign personnel to pour through reams of paperwork to identify the affected products. These paper travelers were handwritten documents, and it was often difficult to read operator names, recorded values, lot numbers, batch numbers and serial numbers because of illegible handwriting, smeared ink or missing values. This information is imperative to a manufacturer as it tries to identify trends to determine the extent of the problem and if it affected certain product batches or lots, or just a few components.
This time-consuming process could take days or weeks, which increased labor and missed opportunity costs. In the mean time, executives cannot accurately discuss the magnitude of the problem to consumers, stockholders and the general public. Without this information, the public could assume that the company might be hiding something, which could shake customer and shareholder confidence and impact future sales and stock prices. Being able to quickly access batch records and device history records is essential. However, the data in these records must be accurate and have the highest levels of integrity to ensure authenticity and validity-especially for life science manufacturers whose products can positively or adversely affect people's health.
Initially, established electronic systems for shop-floor control, material tracking and resource planning used in other industries could not be used for life science manufacturers because it did not comply with FDA regulations. Without FDA electronic record and signature provisions, life science manufactures were forced to continue using pure paper systems, or build homegrown software to collect data electronically, and print and sign these documents manually.
Electronic Record Keeping
In 1997, the FDA released Regulation 21 CFR part 11, which outlined the conditions under which FDA-regulated companies could use electronic records and electronic signatures. This ruling provides guidelines for collecting and storing required records electronically, including the definition of an electronic signature and the rules for executing and storing signatures. With this regulation in place, life science manufacturers were able to take full advantage of electronic manufacturing systems.
The FDA's tracking requirements include either a paperless batch, a device history record or both. The requirement is similar to traditional traceability and genealogy requirements but includes expanded requirements, such as specific definitions. These history records include manufacturing dates, quantities manufactured and released, components consumed and acceptance records indicating that the product was manufactured in accordance with the approved design. The record may also include operator data, such as whether the operators who did specific functions were properly trained, complied with the standard operating procedures and electronically signed off on manufacturing steps.
With this new technology, life science manufacturers have all product information at their fingertips and can count on its accuracy and integrity. If an unforeseen quality problem arises, or if there is a product recall, they can sort electronic history records to identify affected batches, lots, devices, and determine the size and scope of the problem, as well as identify potential causes.
For example, they can determine if the affected products were produced from components purchased from one supplier, if a particular employee worked on the product or if a step was omitted during the manufacturing process. This provides executives with the information they need to address health and safety issues, as well as communicate accurate information to key audiences.
MES technology also enables life science manufacturers to comply with FDA requirements by providing and controlling live data across applications and sites. This information allows managers to make more informed decisions that help improve management of the areas that impact product quality. Manufacturers that implement a MES are complying with FDA regulations and reducing the cost of compliance. In addition, by proactively managing manufacturing processes, manufacturers can reduce process variability.
For example, using a Web-based MES solution brings continuous, real-time visibility of the entire manufacturing process. These systems can identify processing deviations and correct them, leveraging tools including corrective and preventative action (CAPA) and statistical process control (SPC). If the MES detects a problem, it uses pre-defined action plans to notify personnel by e-mail, phone, pager or handheld device so they can take immediate action and prevent more serious problems. If no one responds to the alert, the message is automatically escalated up the chain of command until someone addresses the issue.
By detecting potential problems early through MES trending tools, CAPA and SPC, life science manufacturers can reduce the cost of poor quality. Detection during in-process trending vs. receiving a customer complaint ex-ponentially saves time and money.
Today, the FDA regulatory requirements for electronic data tracking and electronic signature verification for the life science industry have transitioned into an enforcement phase. Manufac-turers are faced with the challenge of implementing electronic systems to ensure FDA compliance. Implementing a MES is not only the key to achieving compliance, it also provides the mechanism to add value throughout the manufacturing process.
One of the key issues for the life science industry is software and system validation. Life science manufacturers need to have the right systems and the right business processes in place to be FDA compliant.
All systems need to be validated before they are put into full deployment. This validation process can be a time-consuming process that can take up to 10 weeks. Because validation is expensive, at times as much as $100,000 or more, some companies delay upgrading their systems until it is absolutely necessary.
Most software systems, because of their design complexity, must be revalidated when an upgrade gets distributed. Revalidation is a costly word and is something both life science manufactures and software vendors hate to hear.
Newer software technology and better system design have significantly reduced the validation process and have all but eliminated the need for revalidation because they have proven to the FDA that an "amended" validation is as accurate and reliable. These systems tend to be out-of-the-box or commercial-off-the-shelf systems that require little to no custom code. More mature software will have configuration capabilities that limit the need for any coding. They typically have high-end configuration modules that allow life science manufacturers to configure the system from one plant to the next, or from one product line to the next, without the aid of the original software developer or an expensive integrator to create custom code.
The more out-of-the-box the solution, the more standardized the validation process can be, knowing that it still must be validated for use. This means that the majority of the validation for a more standardized, flexible product, can be done prior to product implementation. Ultimately, what and how the software is used determines what needs to be validated.
Benefits of MES
A benefit of a MES is design control. MES helps manufacturers ensure that operators follow the process as it was designed by engineering. Deviations are not allowed, or are tracked based on overrides from management. MES includes a modeling engine that allows management to accurately map the physical plant. Because of this, engineering can design all off the operations and steps of the production process and enforce the utilization of this "as-designed" process. In other words, operators are only allowed to do operations that are designed into the system. The MES also allows management to deploy current instructions and specifications to the plant floor to ensure that any changes to the process are incorporated as quickly as possible, with an appropriate and approved process validation.
Leading-edge MES solutions also enable life science manufacturers to synchronize business processes across multiple plants, while allowing for plant-specific variations. A central repository of product definitions enables data collection from multiple plants, so performance across different facilities can be analyzed by product line, product area or other factors, and associated with various operations.
This synchronization also helps companies that use contract manufacturers or use multiple plants to process different steps of the product. The ability to synchronize data as it moves from a contract manufacturer to an OEM plant, or between OEM plants, enables companies to meet the FDA's genealogy requirements.
The stronger MES systems also provide a centralized risk management system that creates a top-down compliance infrastructure for CAPA and complaint management. Most companies use different systems for nonconformance management, CAPA, complaint management, and electronic batch records and device history records. However, the top MES systems contain all of these elements or have connectors that facilitate working with existing systems. Today's manufacturers cannot and should not leave their risk exposure and risk mitigation up to the dependence of replicating data from one system to the next or having individuals monitor more than one system.
The best MES systems tightly tie together existing systems, such as ERP, product lifecycle management, product data management, customer-relationship management and supply relationship management with process and production data. The MES contains the data record, data retention and data retrieval information for all products and processes, ensuring that transactions happen, duplication is avoided and traceability
As the industry continues to become more competitive, minimizing the costs of regulatory compliance will become an important factor for a company's success. Manufacturers that are the most efficient at producing the highest quality products at the lowest cost, while meeting FDA regulations, will be best positioned to succeed. Companies will need a strong manufacturing execution system in order to succeed for the long term.
Sidebar: Tech Tips
1. Life science manufacturers are guided by Regulation 21 CFR Part 820 that addresses quality-related areas, as well as design, process validation, personnel certification, manufacturing and labeling.
2. Initially, records were kept on paper, but electronic record keeping is now in use.
3. A MES helps to comply with FDA requirements by providing and controlling live data across applications and sites.
4. MES systems can identify processing deviations and correct them, leveraging tools including corrective and preventive action and statistical process control.