August 18, 2015 — The FDA has “warned” the three manufacturers of medical endoscopes used in the U.S. for failing to comply with federally mandated regulations.
Last week, the FDA sent warning letters to 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 manufacture, design and oversee the safety of their endoscopes are inadequate.
These letters mark the FDA’s strongest charge against these companies — who market virtually every gastrointestinal endoscope sold in the U.S. — since the FDA first notified the public in early 2015 that duodenoscopes could transmit deadly ‘superbugs’ — most notably, CRE, or carbapenem-resistant Enterobacteriaceae.
Although the FDA’s letters warn these three manufacturers about the safety of their endoscopes and endoscopic accessories, the letters focus on duodenoscopes and most certainly are in direct response to the nation’s recent spate of CRE outbreaks linked to duodenoscopes.
Duodenoscopes are a specialized type of GI endoscope used to perform endoscopic retrograde cholangiopancreatography, or ERCP, more than 650,000 times per year in the U.S. These instruments, which cost $40,000 each, can remain contaminated with superbugs despite being cleaned according to manufacturers’ instructions, according to the FDA.
The mortality rate of patients infected with CRE from a contaminated endoscope can be as high as 50%.
Among other findings, the FDA’s warning letters, each dated August 12, 2015, conclude that these three manufacturers’ devices are “adulterated” or “misbranded” — a finding that raises questions about these devices’ safety and effectiveness.
Each of these three manufacturers’ duodenoscopes has been linked, since 2012, to at least one potentially deadly outbreak of CRE (or a related superbug) in the U.S. following ERCP.
An adulterated device lacks a pre-market approval, or PMA, whereas a misbranded device lacks a regulatory clearance, also known as a 510(k) clearance. Either is required to market a medical device legally in the U.S.
Detailed in these three warning letters, the FDA inspected the facilities of Olympus, Pentax and FujiFilm, both in Japan and the U.S. earlier this year, finding a number of potentially significant safety violations.
According to USA TODAY, these warning letters are a first step toward formal legal action, noting that failure by the manufacturers to correct the cited lapses could lead to administrative orders, fines and federal lawsuits.
FDA spokeswoman Jennifer Dooren told this same newspaper that: “The FDA takes these violations very seriously and will continue to monitor these (three companies) to ensure they take appropriate corrective action.”
Automated endoscope reprocessors (AERs)
The FDA has not publicly discussed the potential regulatory impact of these three warning letters on the manufacturers of another related medical device — namely, automated endoscope reprocessors, or AERs, which are labeled to clean and disinfect, or “reprocess,” the same duodenoscopes whose safety and legal clearances the FDA is now question.
This discussion about AERs and their regulatory status is continued to my related article, “A ‘Trickle-Down Effect’: The Potential Impact of the FDA’s Warning About Endoscope Safety on Automated Endoscope Reprocessors.”
Quality and Safety Services 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.
For their part, each of the three endoscope manufacturers provided USA TODAY with a comment, in response to the FDA’s warning letter:
- Olympus told the paper that the company is “reviewing the FDA’s warning letter so that we can provide the required response in a timely manner.”
- Pentax told the paper that it “consider(s) these issues to be of utmost importance.”
- And FujiFilm told the paper that “actions have been and will continue to be taken to ensure that our products and processes meet FDA requirements, and pose no risks to … health and safety.”
A 3-year reporting delay
Federal regulations require medical companies to report adverse events associated with their devices to the FDA within 30 calendar days. These filed reports are known as medical device reports, or MDRs.
In its warning letter to Olympus, however, the FDA cites the company for waiting three years to inform regulators that 24 patients had been infected with Pseudomonas following ERCP performed using the company’s (uncleared and unapproved) TJF-Q180V model — a type of adverse event that requires the manufacturer to file a MDR, according to the FDA.
This outbreak’s Pseudomonas strain is a potentially deadly superbug that, like CRE, is resistant to carbapenems, a “last resort” antibiotic.
According to the FDA’s warning letter, Olympus “became aware of (this outbreak) on May 16, 2012.” Yet, notwithstanding the regulation’s 30-day time limit, the company didn’t file a MDR until March 2015 — three years later and one month after the FDA issued a national safety alert, in February, 2015.
According to the FDA, its inspection of Olympus determined that the company had no policy for promptly reporting to the Agency adverse events linked to its endoscopes, an FDA requirement.
The FDA’s warning letter to Pentax, too, cites the company for not informing the FDA within 30 days that its duodenoscopes “may have caused or contributed to a death or serious injury.”
More about medical device reports
Endoscope manufacturers may not be the only medical device companies whose reporting of adverse events to the FDA may, at times, not comply with federal regulations, as some manufacturers of AERs also may not have filed a MDR within the 30-day time limit, a review of the FDA’s MAUDE database suggests.
In one instance, Olympus filed a MDR in January 2015 documenting a superbug outbreak linked to ERCP. This report appears to describe the CRE outbreak at UCLA’s Ronald Reagan Medical Center, in Los Angeles (CA), that occurred between October 2014 and January 2015.
USA TODAY reported last March that this Los Angeles hospital was using an AER to reprocess duodenoscopes at the time of its CRE outbreak. Last May, The Los Angeles Times reported that UCLA officials informed the AER’s manufacturer of the outbreak in early 2015, as part of the hospital’s investigation.
Yet, a corresponding MDR filed by an AER manufacturer documenting this adverse event could not be identified in the FDA’s MAUDE database.
A senator, a representative, and expert’s opinions
Weighing in on the FDA’s oversight of duodenoscopes, Sen. Patty Murray (D-Washington) was quoted in a recent Los Angeles Times article (August 17, 2015) as saying: “The patients and families who have been impacted deserve the facts. That’s why I asked the FDA to conduct a full investigation into how this happened in the first place.”
Rep. Ted Lieu (Los Angeles, CA) would seem to agree. In this same The Los Angeles Times article (August 17, 2015), he is quoted as saying: “The fact that it took the leading scope manufacturer three years to report patient infections is flat out unacceptable. If scope manufacturers had reported infections earlier, then lives might have been saved.”
Responding to the importance of timely filing medical device reports, or MDRs, this same newspaper article also presents my perspective: “Prompt reporting of dangerous scope-related infections can save lives. A three-year delay in filing a report is unreasonable.”
And in an USA TODAY article published on August 17, 2015, discussing these three warning letters, I am quoted saying as a Pennsylvania health care consultant (who advises hospitals and medical device manufacturers on safety issues): “The FDA’s actions appear now to be suggesting that this problem is much bigger than they originally thought. It seems like they’re kind of working backwards a bit — as each new shoe drops, we seem to be learning that this should have been getting more attention earlier.”
FDA: Duodenoscopes will remain on the market
The FDA’s safety alert from February 2015 discusses the risk of contaminated duodenoscopes transmitting CRE and other types of deadly multidrug-resistant bacteria during ERCP. According to the FDA, cleaning these instruments in accordance with manufacturer’s instructions reduces — but does not eliminate — the risk of infection.
Ordinarily, the FDA allows manufacturers to market only reusable medical devices that can be thoroughly cleaned an disinfected or sterilized, to prevent disease transmission.
Despite its safety concerns, however, the FDA has stated that it will not remove these censured duodenoscopes from the U.S. market (although the FDA’s decision does not prevent a manufacturer from voluntarily removing its endoscope from the market, to reduce risk and the potential for patient harm).
The Agency wrote in a safety communication issued on February 19, 2015, that “for most patients, the benefits of ERCP outweigh the risks of infection.”
This risk assessment appears fortuitous, at least for one endoscope manufacturer, whose profits have increased despite safety concerns about its duodenoscopes.
In another article, The Los Angles Times reported (August 7, 2015) that: “Embattled device maker Olympus Corp. posted a 14% increase in sales of medical scopes worldwide (in the latest quarter ending June 30, 2015) despite health officials linking its instruments to superbug outbreaks at U.S. hospitals.”
Differing risk assessments
Both the FDA and an FDA advisory panel that convened a 2-day meeting this past May in Silver Spring (MD) assessed the risk of infection from a reprocessed duodenoscope to be “low,” thereby justifying its continued use in the U.S.
Experts have questioned the accuracy of the FDA’s risk assessment, however, and the soundness of any federal actions that are based on this assessment.
USA TODAY (August 6, 2015) quotes Alex Kallen — an infectious-disease physician who coordinates epidemiological investigations at the federal Centers for Disease Control and Prevention (CDC) — as saying: “The number of transmissions is basically unknowable. There is clearly a detection problem in identifying [duodenoscope-related] infection clusters.”
Others might agree, like myself, who stated in a recent Seattle Times article that there could be more potentially deadly infections tied to these devices than suspected or reported, adding, “it is possible that the risk of CRE infections following ERCP is relatively high.”
Also in agreement with the CDC is Kevin Kavanagh, M.D., who heads Health Watch USA. USA TODAY (August 6, 2015) quotes him as saying: “They’re saying the [scopes’] benefit is high, and that’s true, but they don’t really know the risks, because they don’t have solid data on complications. Without knowing the true risks, it’s not really an informed decision. It’s a judgment call.“
Similarly, this same newspaper quotes Lisa Fonkalsrud, president of the Society of Gastroenterology Nurses and Associates, as saying: “Because of the underreporting, we just don’t know the extent of this [duodenoscope] problem.”
A second FDA letter sent to some endoscope manufacturers
CNN has previously reported that the Olympus’ TJF-Q180V duodenoscope model, although still marketed today, is without a legal clearance or approval.
Olympus first introduced this duodenoscope into the U.S. market in 2010. But is was not until 2015 that the FDA publicly questioned this device’s safety and regulatory status.
In addition to the warning letters sent to these three manufacturers, the FDA sent a second letter to FujiFilm and Pentax, also dated August 12, 2015, which concluded that some of their duodenoscopes might, too, be without a legal clearance, just like Olympus’ TJF-Q180V model.
This is the first time the public learned this news.
Examples of FujiFilm and Pentax duodenoscope models that, according to the FDA, might not have a legal clearance, though are in use in the U.S., include the FujiFilm ED-530XT and, possibly, the Pentax ED-3490TK.
While citing both FujiFilm and Pentax for this regulatory lapse, the FDA’s warning letter to Olympus does not mention that its TJF-Q180V model’s lacking legal clearance, although the Agency’s letter does conclude that this model is “misbranded.”
Instead, the FDA’s letter to Olympus focuses only on the company’s handling and timely reporting of adverse events (also known as medical device reports, or MDRs).
The FDA has given the three companies 15 business days from receipt of the August 12, 2015 warning letters to describe the corrective and preventive actions that will be taken by each company in response to the cited violations. No penalties were announced.
Article by: Lawrence F Muscarella, PhD. Posted: 8/17/2015; updated: 8/26/2015, Rev A.
E: Larry@LFM-HCS.com. Twitter: @MuskiePhD