San Jose, Calif.
No other manufacturers face higher stakes with product development than those in the $64-billion medical-product industry. Lifesaving products like cardiovascular lasers and pacemakers leave little room for design errors, and international safety standards provide valuable guidelines for making sure such products are safe and effective devices. Unfortunately, standards can also delay introduction of products by months. And any time lag is too long in an industry where being first to market with patented technology often means the difference between success and failure.
June 1998 brings a new burden to medical OEMs. It marks the first time medical manufacturers must fully comply with new FDA quality process regulations for product design. The good news is that these regulations provide clear guidelines for design and document control.
Recalls lead FDA to action
About 45% of all voluntary medical product recalls are linked to errors in the product design process. When faced with this figure, FDA managers realized how critical the role development plays in a product’s life cycle and significantly revised its Quality Systems Regulation (QSR) rule 820.
Rule 820 has regulated medical product design and manufacturing practices for 20 years. First implemented as the Good Manufacturing Practices (GMP) rule in 1978, it focused on safe manufacturing and product-update practices. After seeing the high number of recalls resulting from initial design flaws, the FDA expanded and renamed the GMP to QSR in 1996. A major addition to the QSR was section (820.30) which covers design control and requires full compliance by June of this year. Under it, medical product manufacturers must be able to show that product designs match initial specifications for use and safety. QSR 820.30 includes three key components:
• Verifying and tracing designs back to original user requirements.
• Keeping regulatory document binders for auditability.
• Maintaining a comprehensive design review process that includes everyone from developers to senior management.
QSR requires that companies “ensure adequate oversight by making verification activities explicit and measuring the thoroughness of their execution.” This means companies should be able to trace the relationships between documents from initial design input through delivering designs to manufacturing. A sample hierarchy might start with a document of requirements that drives two additional documents, one for generating a schematic layout with a subassembly bill of materials (BOM), and a second for generating assembly drawings and work instructions. The schematic and assembly drawings then lead to part and BOM information.
Managing these documents and tracing their relationships manually is a daunting task and prone to error. Product development management (PDM) systems can help companies comply with FDA requirements by integrating process workflow with indexing capabilities to automatically track the design history. This lets medical companies record verification results directly in controlled documents at all stages of the “traceability” tree. Not only does this reduce the time demands on employees, it also makes information instantly available for FDA inspections.
The QSR mandates that design teams, including senior management, approve and sign-off on designs at specific phases during design cycles. Companies that use manual review processes often face bottlenecks in obtaining necessary sign-offs. Bottlenecks typically stem from several sources, including late or missing approvals from individual reviewers, the need to go back and answer questions during the review process, and the sheer inefficiency of manually routing large stacks of documents. Because the penalties for not adhering to processes can range from warning letters to fines to shutting down operations, short cuts are out of the question.
PDM systems can simplify design review and approval processes, whether they are routed through the company or handled as part of formal, face-to-face phase review meetings. Effective systems let review materials be gathered on-line or distributed for early review, and automatically send e-mail notifications. The systems’ workflow capabilities should also make it easy to review design processes on-line. And with electronic signatures, engineers can quickly sign-off on review approvals. Some PDM systems automatically register this approval as part of an on-line design history file, which the FDA requires. Finally, when design output packets are routed for review, PDM systems track the sources of bottlenecks, so they can be quickly resolved.
The new FDA regulations also require clear documentation of the entire product design process, including the design history file, (i.e., the set of files showing design iterations), and the product master record (i.e., a suite of instructions for manufacturing and servicing a product). Traditionally these files have been stored in physical, controlled document binders, which are made available to everyone who needs access, including the FDA, during an audit.
PDM systems, through indexing and document control features, let medical manufacturers replace hard-copy binders with electronic ones. Additionally, PDM Web linking capabilities extend access to geographically dispersed offices. Together, these features make it easy to update binders, keep them current, and make them more accessible. Finally, advanced PDM systems with multi-layered security features can actually improve the security for design records.
FDA Standard: Change Control
Some PDM systems go beyond the FDA’s new design controls and requirements to streamline compliance with other long-standing regulations, including those governing product change control. PDM systems can put engineering change orders (ECOs) into a parallel workflow that takes employees out of endless change review meetings and reduces the time it takes to change a product by 50 to 90 percent. Workflow management also helps managers visualize the complete flow of changes, letting them identify bottlenecks, anticipate the impact on inventory and purchasing, and proactively handle change-induced regulatory notifications. The result is often lower scrap and rework from obsolete parts and inventory. Finally, on-line document control efficiencies in the initial design phase carry over to ECOs.
PDM systems for design control and design document control have been available for a few years. However, a lack of clear guidelines for on-line systems has severely restricted medical manufacturers from fully utilizing these systems. Fortunately, the FDA has recently introduced two additional sets of guidelines that eliminate any concerns regarding non-compliance. These include the QSR section 820.70(i) requirements for validating an on-line system’s intended use, and Part 11 rules on providing secure electronic records and signatures.
QSR section 820.70 (i) provides guidelines on how a data processing system used as part of a quality or production system should be validated “for its intended use according to an established protocol.” The QSR requires intended-use validation for medical products and an industry of consultants has grown up to handle this process. Many of these consultants are expanding their services to validate on-line systems for design control and document control. They setup and test a medical manufacturer’s system according to an established protocol for that manufacturer, provide full documentation of the intended use, and offer third-party certification. Some larger manufacturers may choose to conduct their own intended-use validation. However, many medical companies may find it faster and more cost-effective to use established consulting services.
FDA’s Part 11 rule covers the accepted use of electronic signatures and electronic records. It emphasizes that electronic signatures must be clear, unambiguous, and free from the risk of repudiation. In fact, the FDA requires that all reviewers at a medical firm sign a form stating they fully understand that their electronic signatures carry equal legal weight with written approvals. PDM systems must be able to handle secure electronic signatures and encrypted passwords, not only every time a user comes on-line, but also every time that user needs to electronically sign-off on a design. Part 11 also demands that manufacturers establish a clear audit trail for electronic records, documenting the steps taken and the reviews given in the release or revision of an electronic record. The workflow and document control capabilities in many PDM systems easily address such requirements.
Finding the right PDM system
Different PDM systems focus on different aspects of the design process. Some are better suited than others for design and document control of medical device manufacturers. A few PDM companies recently have begun offering systems tailored to the medical product industry, offering manufacturers the ability to get up and running much more quickly. In reviewing PDM systems, medical product manufacturers should ask these questions:
• What kind of workflow capabilities does the PDM system have to manage the design control process? Without extensive workflow capabilities, a PDM system may not be able to trace verification and user requirements.
• What kind of indexing does it provide? Cross-indexing documents with parts and product-design files is critical in making it easy to satisfy the verification and “traceability” requirements of the FDA and other regulatory agencies.
• How strong are the document control capabilities? This is central to creating and managing on-line versions of the binders required by regulatory agencies for documenting designs and the design process.
• Is the system easily reconfigured to meet new product design demands, or does it require coding? Since a system has to be revalidated for intended use every time the code is changed, configurable systems make it much easier to comply with the FDA.
• How secure are the electronic signatures? Does the system ensure that only approved signers can sign-off on design decisions and reviews?
• Is a medical product industry template included? This template should include a database of FDA terms and a workflow for the design control and design documentation processes. The template can help companies get up and running weeks or even months faster than if those firms had to create their own.
• Is there an intended-use validation service designed to specifically support the PDM system? Because each system is different, availability of a customized service and intended-use protocol significantly shorten the time it takes to complete validation.
New technologies in medical products are bringing exciting new treatments for saving and improving the quality of life. However, the availability of these products is often slowed by the need to meet some of the strictest quality guidelines in the world. With clear FDA guidelines for leveraging on-line systems, PDM solutions help medical manufacturers bridge the gap between the desire to deliver products to market and the demand to ensure safety and effectiveness. Carefully choosing a PDM system that supports FDA QSR requirements not only gives manufactures immediate productivity gains, it also provides the ability to grow quickly as new market opportunities — and new medical technologies — appear.
Faster to market with streamlined product design
Imagine you’re unable to walk down the street without feeling stabs of severe chest pain. For some 90,000 Americans with uncontrollable angina, this is an everyday reality. CardioGenesis Corp., a Sunnyvale, Calif.-based manufacturer, offers hope to these patients with its cardiovascular devices.
The company is currently seeking approval for a series of new transmyocardial revascularization (TMR) devices that treat severe angina. How soon these devices become available to surgeons and cardiologists depends on how quickly the company meets the rigorous controls of the FDA and European CE Mark medical regulatory boards. To streamline both its development and regulatory approval processes, the medical device company has implemented the MedDev PDM system from ConsenSys Software Corp., San Jose, Calif.
The MedDev system has helped trim months from the medical regulatory approval process, which can take three to five years to complete. Since CardioGenesis implemented the system in September 1996, they have used it to get approval of its intraoperative TMR for the European Community by capturing and delivering the necessary CE Mark documentation. It has also let CardioGenesis receive clearance for multi-center clinical trials of its percutaneous TMR device.
“ConsenSys has helped us complete the review of documents related to the European approval process, rapidly providing market opportunities worth hundreds of thousands of dollars to our company,” says CardioGenesis CEO Allen Hill.
Before using MedDev, CardioGenesis relied on a manual paper-driven process that was both inefficient and insufficient. Engineering-change notice approvals (ECNs), which require sign-off by six to eight individuals, typically took several weeks. Moreover, it often took each reviewer several hours to read through the extensive documentation.
With MedDev, CardioGenesis engineers can complete their reviews in just 15 to 20 minutes. Additionally, the new system has eliminated the need for many ECN board meetings, which typically took place two to three times a week. Now executives edit and monitor the approval process online, quickly identifying and resolving bottlenecks from their own workstations. When CardioGenesis managers need to meet, they bring in the MedDev system, so changes can be made in real time to minimize further review cycles.
“The most dramatic benefits are the efficiency of the documentation process and the accuracy in product development made possible with ConsenSys,” notes CardioGenesis CEO Allen Hill. “We’ve seen a dramatic improvement in our ability to solve time-to-market and regulatory challenges while managing our resources effectively.