Facts at a Glance

Company: Large medical device company
Market: Therapeutic apheresis
Challenge: Welding process changes prompted biological safety concerns
NAMSA Approach:

  • Consultation
  • Simulated extractions
  • Analytical chemistry test
  • Gas chromatography–mass spectrometry
  • Toxicological risk assessment

Results: Our planning, testing, analysis, and consulting verified that the welding process change posed no biological safety concerns.

TECHNICAL CHALLENGE

A client had an extracorporeal infusion device with multiple bonded joints in which cyclohexanone and methylene chloride were used as welding solvents. Recent changes to the welding process prompted concerns about safety during clinical use. While these solvents do an excellent job of bonding plastic materials, concerns about potential migration of the solvents during clinical use was very real. More than 35 welded joints had been identified in the product, which created a significant surface area from which the solvents might possibly leach into circulating blood. An additional concern was that the blood would circulate through the device multiple times during its typical two-hour use.

The client asked us to evaluate the device for the presence of two bonding solvents used in the product to determine what impact it would have on patient safety during clinical use (short-term duration, direct contact with bloodstream).

Initial testing showed no significant amounts of the two solvents but did reveal the unexpected (and relatively high) presence of a third chemical. Based on these findings, we quickly consulted the client and suggested that a toxicological risk assessment be performed, which guided the client to a fast and safe resolution. Sometimes during routine testing, it’s not an expected result but an unexpected result that triggers a quick response to an urgent new challenge.

NAMSA’S APPROACH

The client discussed its needs and expectations with one of our technical specialists, who determined that analytical chemistry tests could be used to detect any residual solvents in the bonded joints. However, since the device contained numerous solvent welds and was too large and complicated to extract and test only the bonded joints, the technical specialist decided to design a closed circulation system. Each closed circuit would use one infusion set, simulating extraction to represent the real-time migration of volatile organic compounds from the solvent-bonded joints.

Two circuits were constructed, one using circulating purified water and one with methanol. The two solvents were circulated at 8–10 liters per minute for 2 hours while being maintained at 37 °C. Both circulated solutions were then analyzed using gas chromatography with a purge-and-trap process for residual solvents.

OUTCOME

Of the two known bonding agents, only methylene chloride was found in the circulated solutions. However, the concentration level of the methylene chloride was low enough to cause no biological concern. While the client was happy with these results, an unexpected chemical (2-propanol) was detected during the test. Because of the relatively high concentration of the 2-propanol, we recommended that a toxicological risk assessment be performed.

The potential toxicological concerns were evaluated through a biological safety assessment which showed that very little toxicological concern existed for both the methylene chloride and the unexpected 2-propanol found in the test article circulation solvents. Our planning, testing, analysis, and consulting verified that the welding process change posed no biological safety concerns. After reviewing both the expected and unexpected results, the client implemented the changes to the joint welding process, since they would not pose significant toxicological risk and compromise patient safety.

“This case study is very typical of the daily activities at NAMSA,” says Dr. Dave Albert, Senior Scientist. “We help resolve important issues for our clients, even when the challenge is unexpected. We can react quickly because our scientists offer vast expertise and knowledge in chemistry, microbiology, risk assessments, and toxicology — and have years of experience specifically serving the medical device industry.”

After the manufacturer formally submitted the results, the U.S. Food and Drug Administration accepted that there were no concerns to the safety of end users. As a result, no product had to be recalled or withdrawn from the market. In the end, the manufacturer saved time and money and did not lose sales.