Integrating Quality and the Product Life Cycle into a Single System

SOFTWARE

According to FDA, medical devices are distinguished from other discretely manufactured products because devices are “intended to affect the structure or any function of the body of man.”¹ By contrast, products such as MP3 players, furniture, and children's toys do not carry this weighty burden. An improperly designed or manufactured medical device can quickly lead to serious injury or death. As a result, the industry is highly regulated by FDA in the United States, by the European Council (via the Medical Devices Directive, In Vitro Diagnostics Directive, and the Active Implantable Medical Devices Directive) in Europe, by the New Independent Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, and by similar organizations in other regions.

Despite the presence of highly restrictive regulations, sales of medical devices are growing up to 10% per year in some sectors as a result of an aging population (see Figure 1).² Not only are large numbers of baby boomers swelling the senior citizen population in the United States, Europe, and Japan, but the average life expectancy in these areas is longer than at any time in history. These two factors lead to an attractive current and future market for medical devices.

In addition to competing in a highly restrictive regulatory environment, medical device companies face another challenge, namely the product development process. For better or for worse, new product development has never been so difficult. Product complexity, outsourced development and manufacturing activities, merged companies, and globally dispersed personnel challenge the capabilities of even the most experienced, highly regarded organizations. However, the rewards can be significant for those companies that can conquer the product development process by producing high-quality products on time, within budget, and compliant with applicable regulations.

Product life cycle management (PLM) software can help by allowing companies to collaborate on the creation, configuration, control, and communication of detailed product information using computer-aided design (CAD), computer-aided engineering (CAE), math tools, a single global data repository, and dynamic publishing. These capabilities help in the following ways:

Regulation

Medical device manufacturers that want to sell products in the United States must comply with the Code of Federal Regulations (CFR). Section 21 of the regulations pertains to the oversight of food, drugs, and medical devices. Many parts of 21 CFR pertain to the medical device industry; however, Part 820 is the one part that device manufacturers wrestle with on a daily basis. It describes how medical device companies must adopt quality systems, and it imposes strict requirements on virtually every business aspect of the organization including product design, manufacturing and labeling, personnel training, and supplier and records management, as indicated in Table I. ISO 13485:2003 also addresses quality systems.³ To meet these requirements, the medical device manufacturer's product development and quality systems must be closely aligned and integrated.

21 CFR Part 820. Subpart C describes design control requirements. If design controls are a quality system regulation requirement, and design activities occur as part of product development, then a company's product development system is most effective when integrated with the quality system.

The concept of design controls, document controls, and records are not unique to U.S. regulations. Both the EU and Japan impose similar requirements for the contents of the design history file (DHF), device master record (DMR), and device history record (DHR) as shown in Table II. Together, the information contained in these files comprises the finished medical device.

A second prominent part of 21 CFR that substantially affects medical device manufacturers is Part 11. Part 11 is intended to ensure the accuracy, integrity, safety, security, and authenticity of electronic records and signatures. This regulation applies to many applications of medical device software, including software used in the execution of a medical device company's quality system.

PLM systems, which are designed for rigid change control and security, are generally predisposed to comply with 21 CFR Part 11. However, individual manufacturers are ultimately responsible for establishing specifications and validating compliance with Part 11. Based on individual interpretation, some companies may require capabilities from PLM that are not out of the box, but that can be provided using predeveloped templates.

Some of the more critical Part 11 requirements that PLM fulfills include the ability to generate accurate and complete copies of records, archival protection of records, use of time-stamped audit trails, use of appropriate controls over system documentation, and limiting system access to authorized individuals.

Product Development Challenges

How many medical device companies with successful commercial products have a single location that is home to all product development and manufacturing activities? Today's global business environment dictates that very few medical device companies operate in a single location. Even small medical device manufacturers (<100 employees), which represent more than 80% of all manufacturers in the United States, rely on design or manufacturing partners to develop and manufacture their complex medical devices.⁴

A more realistic approach to developing life-sustaining technology involves design teams in Asia, Europe, and the United States; suppliers in Asia; a centralized corporate regulatory and quality organization; and a single, integrated information technology (IT) department. Design teams (internal and external) must have secure access to the most recent versions of product data, and, given their disparate locations, the information must be routed electronically for review and approval in compliance with Part 11. In addition, this information must be filed and accessible. Part 820 requires companies to maintain a DHF containing the following information pertaining to design:

Part 820 also requires companies to maintain quality records pertaining to complaints, nonconformances, adverse events, audit findings, and corrective and preventive actions (CAPAs).

With all of these FDA requirements surrounding product data, the IT department is crucial to the success of the organization as it is responsible for managing the company-wide systems that create the product data. For example, a firm's enterprise resource planning (ERP) system frequently contains crucial business information such as manufacturing bills of material, routings, sales orders, work orders, and materials resource planning documentation.

Also, many successful manufacturing firms, especially those practicing six-sigma manufacturing techniques, rely upon a manufacturing execution system (MES) to capture vital information about the manufacturing process, thereby enabling companies to track and trend critical process and product parameters.

Other systems commonly used by medical device companies include customer relationship management, supply change management, learning management systems, and, of course, quality management systems. It is difficult to integrate the systems and share data among them—this is where PLM comes in.

Integrating Product Development and Quality Systems

PLM software collects the what-to-build and the how-to-build-it product information in the DHF and DMR, respectively. A significant portion of product information, such as design inputs and outputs, change control documentation, and design verification and validation activities, are mandated by 21 CFR Part 820 and by ISO 13485. Therefore, PLM software plays a critical role in quality system management (see Figure 2). Additionally, maintaining documents of record in electronic format requires compliance with Part 11, and risk management techniques are mandated throughout a medical device's development process per ISO 14971.

In many instances, a change to a device or manufacturing process requires the medical device manufacturer to evaluate actual product design. Storing all quality and product development data in a single repository that fully integrates with the other business applications allows the seamless exchange of information and updates to associated data models such as 3-D models. The result of an integrated PLM and quality system is a closed-loop, auditable quality system, as desired by FDA.

Here are three examples that illustrate the advantages and benefits of having integrated product development and quality systems.

Example 1. This first scenario is a manual, labor-intensive manufacturing process that is neither stable nor capable (i.e., Cpk<1). (The Cpk measures how close a process is running to its specification limits. The larger the Cpk, the less likely it is that any item will be outside the specification.) In the example, production yields are very low and quality problems are frequent. Each nonconformance, adverse event, or complaint results in a CAPA. A cross-functional team's analysis firmly traces the root cause to the operator who, repeatedly, failed to follow the standard operating procedure (SOP) and misaligned the subassemblies. The corrective action in such cases is always to retrain an operator who continues to make the same mistake over and over. Is this approach truly corrective or preventive, or is there a better way to address the problem?

What the team does not realize is that the process suffers from normal, common-cause variation (random, mathematically predictable, resulting from common causes from within the process; e.g., a commute to work requires 25–50 minutes due to common-cause variations such as light cycles, weather conditions, school buses, etc.), which is best solved by either improving the process or changing the specifications. Generally, this latter option is not permissible. Therefore, the team should strive to stabilize the process and establish process capability by reducing the common-cause, normal variation. Because the repeated failures are a result of operators not properly aligning the subassemblies, perhaps the design team should modify the components to include alignment pins to reduce the offset and thus provide better alignment.

As depicted in Figure 3, an integrated CAPA and PLM system in this example would enable a design change as well as all associated changes, such as a revised SOP and updated training records, to be fully traced and directly linked to the CAPA. The result would be improved compliance, reduced risk, improved quality, higher yields, and less scrap.

Example 2. Most CAD software does not have integrated engineering calculation capabilities; therefore, one of an engineer's favorite tools is a lab notebook. These black and maroon hardcover repositories hold documentation of some of the greatest designs of the late 20th century. Unfortunately, extracting important design rationale and calculations for future review or use can be very difficult, especially when the creator has moved on and all that remains is a cryptic lab notebook. Implementing a PLM system that incorporates engineering calculations solves this problem.

In this situation, engineers perform and capture calculations, such as determining the torque required to open a syringe cap, in a software program, and then use the output to drive a 3-D CAD model (see Figures 4 and 5). Jump ahead a few years to a product failure that initiates a complaint forcing an investigation. Accessing the original design calculations, which are stored in the PLM system's DHF, takes minutes. Further, the mechanical design rationale is clearly stated and a conclusion regarding the cause of the product failure is easily determined.

In this example, a PLM system that integrates product development and quality system allows users to link the customer complaint to a corrective action and to the product development files that contain the design inputs and outputs—all in a single, integral system.

Example 3. Typically, the final element in a product development project's Gantt chart is the work breakdown structure that details the required technical publications, such as user guides or service manuals (which are required by 21 CFR Part 820.200). An integrated PLM system that includes dynamic publishing with direct links between native CAD models and technical illustrations greatly simplifies the creation of these documents and ensures closed-loop change control.

For this example, a global in vitro diagnostic device manufacturer elects to update the user interface of a device based on some early customer feedback. A change such as this affects both the design and the technical publications processes. Traditionally, facilitating this change would require the original product model and associated assemblies to be modified, as well as the technical drawings and all references to the original parts or procedures for using the part. Can companies be assured that all instances where the change must occur are identified, controlled, and updated?

In a dynamic publishing environment, a change to a CAD file automatically filters through the technical publication landscape, and all occurrences of the incorrect data are identified and flagged for change to reflect the revised design. Similarly, instructions for use are changed once, which then ripples through all associated technical publications, in all languages, without the need for reformatting. Proper change control is employed throughout with full traceability. Integrating product development and quality systems and associating the design information with the technical publications greatly reduces the likelihood of inadequate change control.

Conclusion

Medical device companies have many options for responding to both government regulations and competitive pressures. As a single repository, PLM software addresses both areas of concern. By capturing design information and quality records in one fully integrated system, companies can employ closed-loop change control when implementing corrective actions.

The benefits of such a solution include increased product quality, reduced product cost, increased speed to market, improved regulatory compliance, and improved audit performance.

David Rubin is director of vertical market strategy at Parametric Technology Corp. (Needham, MA).

References

1. Device Advice, “Is the Product a Medical Device?” [online] (Rockville, MD: FDA, 30 June 1998 [cited 7 July 2007]); available from Internet: www.fda.gov/cdrh/devadvice/312.html.

2. “Implantable Medical Devices” (Cleveland: Freedonia Group, December 2005).

3. ISO 13485:2003, “Medical Devices—Quality Management Systems—Requirements for Regulatory Purposes” (Geneva: International Organization for Standardization, 2003).

4. E-Outlook, “Medical Equipment” [online] (Washington, DC: International Trade Administration, Manufacturing & Services, Office of Heath and Consumer Goods, 2006 [cited 7 July 2007]); available from Internet: www.ita.doc.gov/td/health/outlook_05_medical.pdf.

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