Duodenoscope Makers Get Warning Letters Over Manufacturing, Reporting Problems

Three medical device manufacturers have been warned by federal regulators that they failed to take proper actions that could have prevented or warned the government about deadly superbug outbreaks linked to their products. 

The FDA issued warning letters to Olympus, Pentax and Fujifilm last week, all three of whom make a special type of endoscope called a duodenoscope.

The devices are used in endoscopic retrograde cholangiopancreatography (ERCP) procedures, but difficulties cleaning the devices between patients have resulted in a number of recent outbreaks of antibiotic-resistant hospital-acquired infections.

The companies’ facilities in Japan and the U.S. were inspected in the spring, and investigators determined that Olympus and Pentax both failed to report to the FDA that their devices may have contributed or caused serious injuries or deaths among patients. Both Pentax and Fujifilm were also warned that they had failed to make certain instructions for cleaning their duodenoscopes actually worked.

Olympus released updated cleaning instructions earlier this year.

The letters, issued on August 12, suggest that duodenoscope makers knew for years that their devices were linked to infection outbreaks, but failed to warn the FDA or address the problem. The companies are also currently under investigation by the Department of Justice.

The warning letters come after a number of duodenoscope hospital infection outbreaks have been confirmed, including an outbreak of carbapenem-resistant enterobacteriaceae (CRE) that was revealed in February by UCLA’s Ronald Reagan Medical Center. The outbreak caused at least seven infections, two deaths, and raised concerns that nearly 200 other patients had been placed at risk by duodenoscopes manufactured by Olympus Corp.

The infections have been linked to problems with the “reprocessing” instructions used to clean the devices for use by another patient. FDA reviewers determined that the instructions sent out at the time were inadequate and that even if the recommended steps were followed to clean ERCP endoscopes, flaws in the design may allow them to become easily contaminated.

In addition to failing to tell the FDA that they knew of infections caused by their devices, and putting out instructions that were inadequate, the FDA’s letter to Fujifilm indicates that at least one of its devices was placed on the market without proper approval. The FDA had previously accused Olympus of also failing to get proper approval for one of its endoscope models, and is investigating Pentax to see if that company also failed to meet approval requirements for at least one of its duodenoscopes.

Earlier this month the FDA issued a safety communication expanding cleaning instructions for duodenoscopes used in ERCP procedures.

ERCP Infection Concerns

During the ERCP procedure, the scope is sent through the mouth, down the throat to the stomach and small intestine to drain fluid from pancreatic and biliary ducts. These scopes have been linked to other infections for years.

Another CRE superbug outbreak from infected duodenoscopes occurred in Chicago in 2014. The FDA called on manufacturers to submit test results for review, discovering in some cases the tests were poorly carried out.

In other instances, the cleaning and disinfecting protocol simply failed or was improperly conducted.

Under the 1996 FDA guidance, manufacturers were not required to submit data proving the cleaning protocols were effective and were allowed to set their own standards for effectiveness. The FDA is attempting to focus on this gap in oversight of regulation of medical scope cleaning protocols and potential design flaws.

Specific requirements were imposed by the FDA following the Chicago outbreak, calling for the elimination of 99.999% of microbes at several ovations on the scope.

The outbreaks call into question the safety and reliability of the current cleaning procedures. Following the UCLA outbreak, the duodenoscopes were pulled and a heightened protocol was implemented, one going above and beyond that recommended by the manufacturers.

In May, an FDA advisory committee determined that the devices “do not provide a reasonable assurance of safety and effectiveness” due to the difficulty cleaning them. The panel said that manual cleaning is still important and needs to continue, but also recommended that the FDA reclassify duodenoscopes from semi-critical medical devices to critical medical devices and said reprocessing needs to be taken from “high level disinfection” processes to full sterilization.

Despite the concerns, the panel also determined that the benefits provided by ERCP procedures still outweigh the risks associated with the use of duodenoscopes. They called on the FDA to develop a guide of best practices to make sure that manufacturer instructions are followed, in addition to the need for better instructions overall.

Several duodenoscope infection lawsuits have already been filed  against Olympus over the infections linked to the UCLA outbreak. The complaints allege that design problems that make the scopes especially difficult to clean, placing patients at higher risk of contracting illness.

Exposure to the CRE superbug following an ERCP poses a serious risk of illness, as the bacteria kills 40% to 50% of patients after spreading to the bloodstream.