An infusion pump company considers risk assessment & mitigation

Moshe Ben Yitzhak, MBA, MSc.CGMP Solutions, Ltd.

• Newman Devices is a small start-up company specializing in patient-centric medical devices. Their first product is to be an infusion pump for people suffering from diabetes.

• Using free resources on the FDA’s web site, they recently determined their regulatory path forward. Based on their extensive research, Newman Devices has determined that their infusion pump is a Class II device, and that the 510(k) route is the most direct to approval and market.

• The key employees in this meeting are:

• Dr. Newman, a physician with 35 years of experience, who has specialized in pediatrics and gastroenterology.

• Shelly Smith, a CRA with degrees in Biology and Nursing, who has five years experience with a Big Pharma company.

• Tony Levin, a recently graduated Ph.D., in Chemical Engineering.

Shelly started today’s conversation, “In recent years, FDA’s Center for Devices and Radiological Health (CDRH), has recognized that infusion pumps have significant safety issues. From 2005 through 2009, FDA

received approximately 56,000 adverse events. This included

numerous injuries and deaths. During this time period, firms

conducted 87 infusion pump recalls to resolve safety issues.”

Dr. Newman had hired Shelly to manage the start-up’s QARA department because her background gave her both the scientific and patient-focused skill sets he thought were needed.

Based on the facts she presented, he now understood that

EVERYBODY at Newman Devices had to be dedicated to a “patient first” approach. But how should he proceed now?

Tony added, “the FDA wants design deficiencies to be identified and corrected before they lead to safety problems. It is moving to require manufacturers of infusion pumps to include additional design and engineering information as part of their premarket submission, detailing the steps taken to mitigate risks at each stage of the device’s life cycle.”

“One problem at a time!” Dr. Neyhard, raised his hands as if warding off a blow. “We are only in the design phase. How do we manage risk in the design phase?”

Tony wanted to put his boss at ease, but also wanted him to understand the challenge ahead. “I won’t say it’s easy, but it can be done by implementing risk management as part of the product design process.”

Dr. Neyhard remembered signing off on Risk Management SOP a month before and thought they knew what they were doing, “Let’s review a plan next week.”

After Newman left, Shelly turned to Tony and said, “The safety assurance case is critical. We have to provide a compelling, comprehensible, and valid case that the product is safe for this application, either in a home or hospital setting.”

She went to whiteboard in the conference room and sketched out the following: CLAIM

ARGUMENT(statistical / qualitative)

EVIDENCE(analysis / test data / expert opinion)

In August 2010, CDRH

implemented a pilot

program to explore the

use of an assurance case

framework for 510(k)

submissions for infusion

devices. The assurance

case provides the device

sponsor a systematic

framework for explaining

its product claims, and it

provides FDA the same

framework for reviewing

the safety of the device.

This complements

CDRH’s robust standards

program, which includes

the Application of Risk

Management to Medical

Devices standard (ISO 14971).

Tony knew about the Safety Assurance approach. He had read about it during his post-doc work, but wasn’t sure how to incorporate it in practice. His approach was more technical. “I think the company’s current risk management standard operating procedure is sufficient.”

He continued, “We’ve done the risk mitigation throughout the life cycle so far, we’ve done the validation testing, using FDA’s risk management standard. It requires implementation of a comprehensive safety engineering system that weighs risks & benefits. The standard does not explicitly require an assurance case. ”

Shelly composed herself – this wasn’t the first time they had discussed this, but now it was crunch time. “I don’t disagree, but we need to be confident. This is a start-up and we will only get one shot at this. We need to present the evidence point by point in an organized. The safety assurance case is a map that can get us where we want to go.”

She pressed on, “FDA’s risk management standard requires things like hazard identification and analysis, risk estimation, risk control, evidence of implementation, and risk/benefit analysis — things you’re already doing. By conducting the risk management standard activities within the structured framework of an assurance case, we can assure that there are no gaps.”

“I thought it would be more efficient and cost effective to go the route I was planning,” Tony countered. “I thought we were on the same page.”

“We are,” Shelly replied, “but in this case, it’s more efficient to do more. And really, how much more is it? Like you said, we’re already following the FDA’s guidance. This is just a framework for providing the information.”

Re-packaging all the analysis and test data into a different framework that would address the Agency’s concerns –particular on a type of product that was already on its radar –convinced Tony that a little extra effort was worth it.

A week later, Shelly and Tony were ready.

“Dr. Neyhard,” Tony began, “our risk mitigation strategy covers nine areas of safety concern: electrical, mechanical, software, hardware, operational, environmental, biological/chemical, use, and others to be identified. These nine areas of concern are the results of a comprehensive risk assessment effort based on a top-down approach called Fault Tree Analysis and a bottom-up approach called Failure Modes and Effects Analysis.”

“It references the most current versions of standards, like IEC 60601 series for electrical safety, IEC 62366 for usability, ISO/IEC 15288 for software life cycle.”

“All evidence of our work will be documented in a risk management report,” nodding to Shelly, “we will summarize all our findings in a safety assurance case report.”

Clicking on the computer, he advanced to the next slide in the presentation.

“This is one of the nine areas we have worked on. It’s an electrical risk assessment to support a safety assurance case. The team followed the company’s quality management system SOPs that state the FDA’s risk management requirements. We analyzed the pump in the context of its intended use. We then identified some of the hazards and hazardous situations associated with electrical safety. We estimated the risk associated with electrical safety that could result in potential user burns.”

“The team has proven that the device is reasonably safe from electrical hazards and hazardous situations that might cause burns. The mitigation strategies were focused on the pump design,” Tony said gesturing at the slide.

The pump was designed with fuses that protected the side pumps and main pumps from short circuit conditions.

The circuitries were designed according to specifications, and the fuses were tested and shown to effectively protect the pumps.

“All relevant records including design schematics, description of risk control measures, and demonstration of implementation and effectiveness were recorded in the verification and validation protocols and reports.”

“The documented evidence supports an argument that the user is free from unacceptable risk of burns at present, but additional hazards need to be identified and mitigated.”

Dr. Newman stared at the slide, tracing the logic, then asked, “Tony, why aren’t there circles beneath some of the squares? Are there no associated risks?”

“No, the engineer replied, “Those are the claims we are still working on. We expect to complete them in a couple of weeks. I’ll set up another meeting in a week so we can review them.”

“This is a very good start,” said Dr. Newman. “I want everyone in this company to focus not only on complying with regulations, but on showing that our devices are safe!”

https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm209337.pdf

www.fda.gov/medicaldevices/productsandmedicalprocedures/generalhospitaldevicesandsupplies/infusionpumps/ucm202501.htm

www.fda.gov/medicaldevices/productsandmedicalprocedures/generalhospitaldevicesandsupplies/infusionpumps/ucm202501.htm

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/detail.cfm?id=33613

For purchase from ISO:

https://www.iso.org/standard/53940.html