CVRx is developing a second-generation system to provide Baroreflex Activation Therapy. This system, called XR-1, will be evaluated to determine its efficacy and safety. After using IBM® Rational® DOORS® as the Soluzione PTC per requisiti e convalida engineering platform for approximately one year, CVRx replaced it with Integrity. CVRx selected Integrity for its flexibility, integration of multiple disciplines in a single solution and capacity to provide comprehensive traceability between artifacts. By using Integrity, CVRx has compressed development cycles, improved productivity, mitigated risk, and streamlined regulatory and internal reporting.
As a privately held company that is venture capital funded, CVRx must move its development projects quickly to clinical trials — without sacrificing quality — due to long regulatory approval cycles. Ultimately, accelerating time-to-market is key to providing a return on investment by expanding or establishing new markets within tight cost constraints. With an aging population worldwide, and an estimated 73 million Americans alone suffering from hypertension-related heart issues — at an annual cost of $69.4B — the XR-1 System could have huge ramifications for human health, quality of life, lifespan and the economics of healthcare.
The XR-1 System 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 these signals as a rise in blood pressure. In response, the brain then sends signals 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 — scientific trials designed to ensure the product is both safe and effective. The XR-1 System is investigational and is being implanted in ongoing clinical trials in Europe.
Since 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 European Union requires a similar set of documentation called a “Technical File.”
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 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 Soluzione PTC per requisiti e convalida and, based on prior knowledge of the product and its capabilities, CVRx selected IBM Rational DOORS, a wellknown Soluzione PTC per requisiti e convalida tool. However, after using DOORS for approximately one year, CVRx required an engineering documentation and development platform that was more flexible, configurable and customizable — and one that also facilitated requirements reuse. As the project evolved, CVRx recognized a
growing need for a broader toolset capable of more than simply Soluzione PTC per requisiti e convalida.
An example of an exported hazard report from Integrity.
To meet compliance regulations and ensure quality while still maintaining an aggressive schedule, CVRx needed a comprehensive solution that could manage its requirements, specifications, test cases, change requests, defects and other documents, processes and records — as well as automate compliance reporting. Assembling the necessary documentation while providing the required traceability between engineering artifacts can be a daunting task, but it is essential in effectively managing and evaluating risk and ensuring that only safe and viable medical devices reach the consumer.
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 Integrity — a comprehensive, integrated solution that could meet current needs and be flexible enough adapt to changing requirements as the business evolved and grew. In addition, Integrity could provide traceability between disciplines, which is necessary in effectively managing risk. Regulatory reporting requirements could be easily automated with customized “one-click” reports. Integrity’s ability to leverage existing code between engineering projects would support shortening iterative development cycles to six months.
In 2008, CVRx replaced IBM Rational DOORS with Integrity for Soluzione PTC per requisiti e convalida. Based on initial success and the desire to manage multiple engineering artifacts with one application, the scope of Integrity was broadened to include source code management, with ties to tasks and workflow management between requirements and source code. As such, risk management, development issue management, and standards requirements capabilities — as well as capabilities for 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.
All these artifacts are now linked through 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) were created. This work will be leveraged in future projects, accelerating development and time-to-market. In February 2011, the first XR-1 System that used Integrity for development from start to finish was implanted.
- Full traceability across such critical aspects as requirements, risks, mitigations and source code facilitates risk analysis, management and reporting
- Risk Priority Number (RPN) tracking supports System Risk Analysis and Failure Mode and Effects Analysis (FMEA) and ensures safety and quality
- Use of one platform to support multiple engineering roles reduces cost to implement, maintain and manage
- Generation of a DHF can be accomplished without without requiring additional personnel
- 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 (e.g., protocols) enable sixmonth project lifecycles
The Next Steps
Due to the success of this project, Integrity will be 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.
For more information, visit Integrity