Successfully Managing Risk, Accelerating Time to Market

Baroreflex Activation Therapy is an active implantable for the treatment of high blood pressure and heart failure.CVRx, a privately held medical device company in Minneapolis, MN, is developing a second-generation system to provide Baroreflex Activation Therapy – active implantable technology for the treatment of high blood pressure and heart failure. This system, called XR-1, will be evaluated to determine its efficacy and safety. After using IBM Rational Doors as the requirements manage­ment-engineering platform for about a year, it was replaced with PTC's Integrity. CVRx selected PTC's Integrity for its flexibility, inte­gration of multiple disciplines in a single solution, and capacity to provide compre­hensive traceability between artifacts. By using PTC's Integrity, CVRx has compressed development cycles, improved productiv­ity, mitigated risk, and streamlined regula­tory and internal reporting.

"We just completed an ISO 13485 compliance quality review with a global certification organization," says John Stroebel, technical fellow, systems engineering, CVRx Inc. "PTC's Integrity manages all our customer and product specifications, verification testing, risk assessment, AIMD and CMDR essential requirements and harmonized standards documentation, and it provides complete, real-time traceability, resulting in a quick and successful audit, enabling my team to stay focused on development."

The Technology
With an aging population, and an estimated 73 million people in the United States alone suffering from hypertension related heart issues at a cost of $69.4 billion each year, this device could have huge ramifications to human health, quality of life, lifespan, and the economics of healthcare.

The XR-1 aystem is an implantable technology that electrically activates the body's system for regulating blood pressure. Signals are sent to the central nervous system and the body interprets this as a rise in blood pressure. The brain then sends signals in response to dilate blood vessels. This allows blood to flow more freely, reducing the heart rate and encouraging the kidneys to release fluid.

The XR-1 system is a Class III medical de­vice, an FDA classification that indicates it could support or lengthen human life, pre­vent a serious health issue, or potentially pose a significant health risk if not properly evaluated. Class III devices are subject to the most stringent FDA regulation and are subject to premarket approval, requiring scientific trials designed to ensure the product is safe as well as effective. The XR-1 system is investigational and is being implanted in ongoing clinical trials in Europe.

Because it is a Class III medical device, the XR-1 system is subject to the reporting requirements of the FDA Code of Federal Regulations (CFR) 21, which stipulate that a design control plan must be in place for new product development. As part of this, procedures on design, design history, product requirements, specifications, test plans, and change control must be docu­mented in a design history file (DHF) and a device master record (DMR).

The Challenge
The company's initial engineering platform was designed for research purposes with all documentation based on Microsoft Word. In 2007, CVRx embarked on a project to architect a new flagship product (XR-1) to replace the current research system and create a viable commercial platform. The new design would deliver the same therapy but would use new electronics, a new mechanical design, new external instrumentation, and new firmware and software.

The launch of XR-1 created an immediate need to automate requirements manage­ment, and based on prior knowledge of the product and its capabilities, CVRx selected IBM Rational DOORS, a well-known requirements management tool. However, after using DOORS for about a year, CVRx required an engineering docu­mentation and development platform that was more flexible, configurable, and customizable, which also facilitated require­ment reuse. As the project evolved, CVRx recognized a growing need for a broader toolset capable of more than just require­ments management.

In order to meet compliance regulations and ensure quality while still maintaining an aggressive schedule, CVRx needed a comprehensive solution that could man­age their requirements, specifications, test cases, change requests, defects, and other documents, processes, and records, as well as automate compliance reporting. Assembling the necessary documentation as well as providing the required trace­ability between engineering artifacts can be a daunting task – but is necessary to effectively manage and evaluate risk and ensure that only safe and viable medical devices reach the consumer.

The Solution
By standardizing on a single engineering documentation and development platform, rather than implementing several different tools, CVRx would gain full collaboration and communication capabilities across the engineering organization and across the lifecycle.

This decision led CVRx to select PTC's Integrity – a comprehensive, integrated solution that could meet current needs while being flexible enough to adapt to requirements as the business evolves and grows, providing trace­ability between disciplines, necessary to manage risk. Regulatory reporting requirements could be easily automated with customized one-click reports, and PTC's ability to leverage existing code between engineering projects would support shortening iterative development cycles to six months.

In 2008, CVRx replaced IBM DOORS with PTC's Integrity for requirements manage­ment. Based on initial success, and the desire to manage multiple engineering artifacts with one application, the scope of PTC's Integrity was broadened to include source code management with ties to tasks and workflow management between requirements and source code. Next, risk management, development is­sue management, and standards require­ments (and linking standards to those requirements that satisfy the standards) were added to the platform. Finally, in 2009 CVRx moved their quality manage­ment processes and documents into In­tegrity, creating a complete, end-to-end development management system.

Now all these artifacts are linked through PTC's Integrity, enabling traceability from risks to mitigations to requirements, source code, and verification tests. As part of the project, many new processes have been defined and documented and dozens of standard operating procedures (SOPs) and work instructions (WIs) created. This work will be leveraged in future projects, speed­ing development and time-to-market. In February 2011, the first XR-1 system was implanted that used PTC for development from start to finish.

The Results

• Full traceability across requirements, risks, mitigations, source code, etc. facilitates risk analysis, management, and reporting
• Risk Priority Number (RPN) tracking supports System Risk Analysis and FMEA and ensures safety and quality
• Use of one platform to support mul­tiple engineering roles reduces cost to implement, maintain, and manage
• Generation of Design History File (DHF) can be accomplished without ad­ditional headcount
• Rapid response capability to regula­tory audits preserves time-to-market pro­jections and positions CVRx for growth
• Ability to reuse assets such as source code, requirements, specifications, and test suites (protocols) enables six-month project lifecycle

"PTC's Integrity fulfilled all of our needs in one comprehensive engineering platform. We are able to manage requirements, product specifications, development issues, and tasks, standards requirements, testing, risk management, and analysis," Stroebel says. "By using one tool instead of multiple tools, we have the traceability that we need between engineering arti­facts, and we can create custom reports that show the linkages between various engineering elements."

Next Steps
Based on the success of this project, PTC's Integrity is being deployed across the entire CVRx development organization. Additional custom reports will be created and refined and role-based viewsets will be designed and customized for improved ease-of-use and simplified management.

PTC
Needham, MA
ptc.com

CVRx
Minneapolis, MN
cvrx.com