October 6, 2015 — Yesterday the U.S. Food and Drug Administration (FDA) ordered the three manufacturers of certain specialized medical endoscopes sold in the U.S. to perform “postmarket” surveillance studies.  This order was made public via a FDA News Release.

CRE (From: CDC)

These endoscopes, called duodenoscopes, are used an estimated 650,000 times per year in the U.S. to perform endoscopic retrograde cholangiopancreatography, or ERCP.

A primary objective of the FDA’s ordered studies is to determine the percentage of duodenoscopes that remain contaminated with ‘superbugs’ and other types of bacteria after being cleaned and disinfected — or reprocessed — as instructed by the device’s labeling.

The collected data will presumably be used by the FDA to complement the previously published studies of others, which found that two of 8 reprocessed duodenoscopes (25%) remained contaminated with CRE.

ERCP is a gastrointestinal procedure commonly used to diagnose and treat diseases of the pancreatic and biliary ducts.

Duodenoscopes under federal scrutiny

The designs of duodenoscopes have come under intense federal scrutiny the past year after the public became aware of a number of deadly superbug outbreaks — most notably, those caused by the CRE bacteria — that officials had linked to contaminated duodenoscopes used at hospitals in Seattle, Pittsburgh, and near Chicago.

Arguably the most publicized of these CRE outbreaks — identified in late 2014 at UCLA’s Ronald Reagan Medical Center, in Los Angeles — was first reported on-line by The Los Angeles Times on the evening of February 18, 2015. The article appeared the next day on the paper’s front page.

Later that same day, on February 19, the FDA issued a safety communication concluding that a contributing factor to these outbreaks was the design of duodenoscopes, which may impede their effective cleaning.

In this communication the FDA ominously acknowledged that the reprocessing of duodenoscopes will reduce — but may not entirely eliminate — the risk of transmitting infections during ERCP.

Identified for the first time in the U.S. in 2001, CRE, or carbapenem-resistant Enterobacteriaceae, is an emerging pathogen that not only has developed a resistance to virtually every antibiotic, but may also remain on duodenoscopes despite these devices being reprocessed as instructed by their manufacturers, the FDA has concluded.

The mortality rate of some patients infected with CRE can be 40%, or higher. One study investigating an outbreak of CRE following ERCP linked to contaminated duodenoscopes reported a mortality rate among infected patents of 50%.

Warning letters

Yesterday’s FDA order follows on the heels of another recent FDA action.

In August, the FDA sent warning letters to the three manufacturers of duodenoscopes used in the U.S. — Olympus America, Inc., FujiFilm Medical Systems, U.S.A., Inc., and Hoya Corp. (Pentax Life Care Division) — formally highlighting the Agency’s concerns that some of the practices these companies currently employ to oversee the safety of their devices do not comply with federal regulations.

Along with yesterday’s FDA order, August’s warning letters mark the FDA’s strongest action against these companies — who market virtually every gastrointestinal endoscope sold in the U.S. — since the FDA issued its aforementioned safety communication last February concluding that the designs of duodenoscopes may hinder effective cleaning.

Warning letters of this type can be the first step toward formal legal action. More of the details of these warning letters may be read in my article, “FDA Warns Three Endoscope Manufacturers for Safety Violations Following Deadly ‘Superbug’ Outbreaks.”

Scopes will not be recalled

Despite the difficulty cleaning them, however, the FDA has decided not to remove duodenoscopes from the U.S. market.

In March, the FDA was quoted to say that “more than 500,000 of these procedures (ERCPs) are done every year in the U.S., and the risk of bacterial transmission is actually really very, very low. We believe the benefits outweigh the risks,” CNN reported.

Providing an alternative, if revised, explanation for the FDA’s decision not to remove these devices from the market, yesterday’s FDA news release states that “as there are no alternative devices for ERCP, the FDA believes at this time that the continued availability of duodenoscopes is in the best interest of the public health.”

Close-up view of an ERCP endoscope tip
Image of a duodenoscope.

[This statement by the FDA raises the reasonable question whether the Agency would have ordered the recall of duodenoscopes earlier this year if other competing types of legally marketed devices were available to perform ERCP.]

According to yesterday’s FDA news release, the three manufacturers of duodenoscopes sold in the U.S. have 30 days to submit their respective postmarket surveillance plan to the FDA.

Quality and Safety Services and Case Reviews for Hospitals, Manufacturers, Patients:  Click here to read about Dr. Muscarella’s quality and safety services committed to reducing the risk of healthcare-associated infections, including CRE outbreaks linked to contaminated endoscopes and other reusable medical equipment.

Section 522 of the Act

The FDA’s ordered studies are called “postmarket” surveillance studies because duodenoscopes have already been cleared by the FDA for marketing in the U.S. In contrast, a manufacturer would perform “premarket” testing to evaluate the performance of a device prior to its marketing in the U.S.

Under Section 522 of the Federal Food, Drug and Cosmetic Act (or, “Act”), the FDA may order a manufacturer of many types of devices, including duodenoscopes, to conduct postmarket surveillance studies, such as stated in yesterday’s FDA news release, provided the device’s failure is reasonably likely to have serious adverse health consequences, or if the device meets one of three other criteria (which may be read by clicking here).

There are a number of other types of postmarket surveillance strategies that may be employed to address a public health concern, including the active surveillance of adverse events associated with a device, or “bench testing,” which investigates a device’s wear and fatigue when physically stressed.

Yesterday’s FDA order does not discuss any of these other tests, appearing to require the endoscope manufacturers only perform postmarket surveillance studies. More of the details of the FDA’s order directed at duodenoscope manufacturers are provided in the yesterday’s FDA press release.

Discussion: Automated endoscope reprocessors (AERs)

The intent of the FDA’s order to have the three endoscope manufacturers perform these postmarket surveillance data seems well-taken and might improve pubic health. But, some aspects of this order’s scope and methodology may be reasonably questioned.

First, by one report’s estimate, as many as 90% of duodenoscopes used in the U.S. are reprocessed using an automated endoscope reprocessor, or AER.  The rationale for the FDA’s order focusing exclusively on endoscope manufacturers — without having apparently asked the manufacturers of AERs to participate and provide guidance and adjunct data — is unclear.

Three weeks ago, the FDA acknowledged in an article in USA TODAY that the Agency had recently directed the manufacturers of AERs to perform more rigorous tests to validate the effectiveness of their machines for reprocessing duodenoscopes. No matter, yesterday’s FDA order is directed exclusively at the three duodenoscope manufacturers.

In response to the FDA’s order, a reasonable scenario can be envisioned in which the duodenoscope manufacturers might assert, within the 30-day allotted time, that it cannot provide the Agency with the requested surveillance plan, or with any other meaningful information or data.

In this scenario, the manufacturers’ rationale would be that, as manufacturers of endoscopes, each oversees and validates the effectiveness of the manual reprocessing of these devices — not their automated cleaning or disinfection (unless the endoscope manufacturer also markets an AER, which is the exception).

Indeed, the majority of U.S. hospitals today use one of several AER models to reprocess duodenoscopes. Moreover, as USA TODAY has reported, every duodenoscope linked to an outbreak of CRE in the U.S. since 2012 was reprocessed by an AER.

(The FDA has expressed concerns about the safety of automated processing. Based on an FDA inspection last April of at least one manufacturer of an AER — I discuss this in a related article, — it appears that one or more AER models currently in use in U.S. hospitals were not validated for reprocessing duodenoscopes.)

A federal probe

Second, in response to the FDA’s order, the duodenoscope manufacturers might further assert within 30 days that they have little meaningful information to provide the Agency, because doing so could be legally incriminating.

The Los Angeles Times reported last May — as USA TODAY similarly did in June — that last spring the U.S. Justice Department served subpoenas to each of the three duodenoscope manufacturers as part of an ongoing federal probe into the circumstances of these several deadly superbug outbreaks linked to ERCP.

(Source: U.S. Justice Department)

Moreover, these three endoscope manufacturers, like any publicly-traded company (at least those in the U.S.), would reasonably be circumspect and might hesitate before collecting postmarket surveillance data that could publicly reveal a flaw in their instructions or validation testing, or in the the design of their duodenoscopes, especially in light of this on-going federal probe.

Whether right or wrong, a primary corporate responsibility of these companies would be to exonerate and indemnify, not to potentially implicate or publicly disparage, one of their marketed endoscope models.

Potential testing conflicts

And, third, yesterday’s FDA order instructs the endoscope manufacturers to perform these surveillance studies in the clinical setting with no independent oversight.

Indeed, the order does not include complementary testing being performed by hospitals, or a firm or organization, that does not present a potential conflict of interest — for example, a group of non-profit hospitals with no ties to any of the three endoscope manufacturers.

In short, if the endoscope manufacturers perform the studies the FDA ordered yesterday, questions will likely be asked about the potential for inadvertent bias and whether additional, independent testing would be required to validate the manufacturers’ collected data.

Closing remarks

The FDA’s order to collect postmarket surveillance data seems prudent and worthy in intent. But, its scope and methodology may prove to be too limiting and to hinder the collection of scientifically sound, meaningful data.

The FDA’s use of one or more independent organizations or hospital groups that would impartially collect these surveillance data would mitigate some of the order’s potential shortcomings.

And, based on the goal of these ordered surveillance studies — “to better understand how (duodenoscopes) are reprocessed in real world settings,” — it can be argued not only that adjunct data are important to collect, but also that the manufacturers of AERs might record a more accurate pulse of endoscope reprocessing practices in today’s U.S. hospitals than the endoscope manufacturers.

Article by: Lawrence F Muscarella PhD, posted: 10/6/2015; updated: 10/13/2015, Rev A.

Lawrence F Muscarella, PhD, is the president of LFM Healthcare Solutions, LLC, a solution-oriented company with the objective to improve healthcare safety through evidence-based consultations. Click here for more details.

Email: Larry@LFM-HCS.com; Twitter: @MuskiePhD

2 thoughts on “FDA Orders Endoscope Manufacturers to Perform Safety Studies”
  1. “But, its scope and methodology may prove to be sufficiently limiting as to hinder the collection of scientifically sound, meaningful data.

    The FDA’s use of one or more independent organizations who would impartially collect these surveillance data would seem to mitigate several of the order’s potential shortcomings. ”
    Keen observation Dr. Muscarella! It is foolish to expect the fox to inspect the hen house, as the saying goes. Vanderbilt, Cleveland, TDH and Johns Hopkins all contracted independent testing in 2001 to discover several Olympus bronchoscope model s could not be cleaned and were defective as designed leading to recall. If OAI’s safety and risk director could not admit their devices were responsible for infections, injury and deaths for the prior 10+ years – what changes? The change here is that the FDA has now acknowledged the 3 manufacturers can continue to use the scopes with no independent testing. FDA Rubber Stamped collateral damage?

  2. Yes Dr. Muscarella, keen observation! All these recent publications by CDC and FDA give the impression that they’re just saying oops we goofed, let’s put something down in writing to shield ourselves in the future, being sufficiently vague to leave plenty of room for interpretation and bias.

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