Duodenoscope Infection Warnings Could Have Been Issued Earlier, FDA Reviewers Say

Federal investigators indicate that the FDA knew about the risk of problems with duodenoscopes as early as the Fall of 2013, when outbreaks of treatment-resistant bacteria were linked to problems with the cleaning specifications provided for the endoscopic devices. However, the agency did not issue warnings until this year, after several deaths among patients at UCLA Medical Center. 

The findings were outlined in a report filed by FDA reviewers ahead of a May 14-15 meeting of the agency’s Gastroenterology-Urology Devices advisory committee, which was scheduled in response to a series of recent duodenoscope infections among patients who underwent an endoscopic retrograde cholangiopancreatography (ERCP) procedure.

According to the report’s executive summary (PDF), released on May 5, the FDA was first warned in late 2013 that the devices may spread infections even after being cleaned in accordance with instructions provided by the manufacturers.

The first public warnings about the issue were not released until concerns arose earlier this year over the reprocessing of duodenoscopes after an outbreak of deadly carbapenem-resistant enterobacteriaceae (CRE) infections at UCLA Ronald Reagan Medical Center. The hospital reported that two patients had died and several had been sickened by the antibiotic-resistant infections, and sent warning letters to 180 patients that could have been exposed.

Shortly after, other hospitals announced they had tracked infections back to duodenoscopes as well, particularly those manufactured by Olympus. However, the FDA appears to have already known there was a problem.

“The Centers for Disease Control and Prevention (CDC) alerted the FDA to a potential association of multi-drug resistant bacteria and duodenoscopes,” according to the report. “Upon further investigation, FDA learned that these new cases of infection were occurring despite confirmation that the users were following proper manufacturer cleaning and disinfection or sterilization instructions. FDA communicated with federal partners, manufacturers, and other stakeholders to better understand the critical factors contributing to these infections and how to best mitigate them.”

The report indicates that, and a review into the history of duodenoscope approval within the FDA’s 510(k) fast track approval process, all took place in the fall of 2013 and the winter of 2014. Later in 2014, the FDA even began working with the CDC and the U.S. Environmental Protection Agency (EPA), identifying all High Level Disinfectant (HLD) manufacturers and developing testing methods and protocols for their analysis.

The FDA did not issue a safety communication on duodenoscope cleaning problems until February 19 of this year.

Duodenoscopes are flexible, lit tubes that are inserted down the throat to the top of the small intestines for gastrointestinal procedures. They allow contrast dye to be injected and can be used with other medical instruments to retrieve biopsy samples. The FDA estimates that more than 500,000 ERCP duodenoscope procedures occur each year in the U.S.

The FDA warned that the design of the devices, which includes a movable “elevator” at the tip, may trap pathogens and blood even when recommended cleaning techniques are used.

When the safety communication was issued, the FDA revealed that from January 2013 through December 2014, it received 75 reports of infections that affected about 135 patients linked to the use of the devices. However, the problems may go back even further.

In 2009, the FDA issued an advisory to health care professionals following an infection outbreak that affected 16 patients in France following duodenoscope procedures. In 2012, duodenoscope use was linked to an outbreak at the Moffitt Cancer Center in Tampa, Florida, where four patients were infected with drug-resistant pathogens.

The advisory meeting’s goal is to have health care experts discuss the effectiveness of cleaning, high level disinfection and sterilization methods for duodenoscopes. The panel will also discuss how much premarket information the FDA needs to ensure that the cleaning instructions are adequate before approving future duodenoscopes, best practices and guidelines for cleaning, known as reprocessing, and whether other risk mitigation efforts, like surveillance cultures, will be necessary.

The advisory committee’s findings are not binding on the FDA, but the agency often weighs its’ advisors recommendations heavily before finalizing new rules and regulations.

Olympus Duodenoscope Infection Lawsuits

Several of the major outbreaks have been linked to duodenoscopes made by Olympus and used during ERCP procedures.

A number of hospital infection lawsuits have been filed against Olympus in recent weeks by either former patients who were infected after ERCPs or by the family members of patients who died due to ERCP duodenoscope infections. The lawsuits accuse Olympus of negligence in failing to provide adequate cleaning instructions to hospitals, or failing to properly design its duodenoscopes.

In late March, the FDA announced that Olympus had successfully validated new reprocessing instructions for some of its duodenoscopes.

The new reprocessing instructions focus on the Olympus TJF-Q180V duodenoscope, which has been linked to at least two outbreaks. The FDA approved the new validation instructions despite the device not being properly approved for use.

The new instructions involve raising and lowering the elevator for the duodenoscopes several times while immersing them during precleaning and significant increases in the amount of manual brushing, flushing procedures, flushing volume and other measures. The company is also sending out a new brush for cleaning the elevator recess area.

The FDA is recommending that hospitals put the new cleaning instructions into use immediately and to train the appropriate staff on the proper cleaning of the duodenoscopes as soon as possible.