Folks, it appears the ongoing saga associated with the use and subsequent reprocessing of duodenoscopes has reached the next phase: A request to perform postmarket surveillance studies from FDA. The three manufacturers (that were previously awarded with the prestigious FDA Warning Letter)—Olympus America, Inc., Fujifilm Medical Systems, U.S.A., Inc., and Hoya Corp. (Pentax Life Care Division)—have 30 days to submit their postmarket surveillance plans to the agency. The plans shall include details on the performance of additional clinical studies to evaluate how well health care professionals are “following instructions to clean and disinfect duodenoscopes between patients; and to better understand the rate of contamination of clinically used duodenoscopes.” First off, please do not confuse the agency’s request for postmarket surveillance studies, as delineated in accordance with 21 CFR, Part 822; versus what the European Union considers a postmarket surveillance program, MEDDEV 2.12-1. The concept is quite different. In fact, it is Dr. D’s humble opinion that effort would equate to comparing apples and fragmentation grenades. The agency’s proclivity (look-it-up) to pursue action in regards to reprocessing scopes is becoming readily apparent. Unfortunately, it is a little too late for those that have lost loved ones as a result of dirty scopes being employed in procedures. Enjoy!

FDA Press Release Excerpt

“The U.S. Food and Drug Administration today ordered the three manufacturers of duodenoscopes marketed in the U.S. to conduct post-market surveillance studies to better understand how the devices are reprocessed in real-world settings.”

“This is a significant step in the effort to combat infections spread through duodenoscopes. The FDA has undertaken an in-depth investigation into the factors that may play a role in infection transmission associated with duodenoscopes, and is now requiring manufacturers to study the devices in the clinical setting where they are being used,” said William Maisel, M.D., M.P.H., deputy director for science and chief scientist at the FDA’s Center for Devices and Radiological Health. “These studies will provide critical information about the effectiveness of current reprocessing instructions and practices that may provide additional information to inform the FDA’s actions to protect the public health and help reduce the risk of infections.”

“The three manufacturers – Olympus America, Inc., Fujifilm Medical Systems, U.S.A., Inc., and Hoya Corp. (Pentax Life Care Division) – that market duodenoscopes sold in the U.S will have 30 days to submit post-market surveillance plans to the FDA. These proposals must detail their plans to conduct studies to evaluate, among other things, how well health care personnel are following instructions to clean and disinfect duodenoscopes between patients and to better understand the rate of contamination of clinically used duodenoscopes. These studies are based on the FDA’s current understanding of factors that may be contributing to infection outbreaks following endoscopic retrograde cholangiopancreatography procedures (ERCP), as well as the information needed to help fill gaps in knowledge.”

21 CFR, Part 822 – Post Market Surveillance

“This part implements section 522 of the Federal Food, Drug, and Cosmetic Act (the act) by providing procedures and requirements for post-market surveillance of class II and class III devices that meet any of the following criteria:

(a) Failure of the device would be reasonably likely to have serious adverse health consequences;

(b) The device is intended to be implanted in the human body for more than 1 year; or

(c) The device is intended to be used outside a user facility to support or sustain life. If you fail to comply with requirements that we order under section 522 of the act and this part, your device is considered misbranded under section 502(t)(3) of the act and you are in violation of section 301(q)(1)(C) of the act.”

Compliance for Dummies

Unlike the European Union, FDA will notify a device establishment when it believes postmarket surveillance for a specific device is warranted. The letter (actually, it is an order) coming from the agency will be for a specific device or device family. If you disagree with the FDA’s request, you can appeal. However, Dr. D wishes you the best of luck with your appeal. Please let the doctor know how the review process and/or special hearing goes; however, the doctor already knows that answer: “Denied!”

Once an establishment receives their letter/order from FDA requesting that a postmarket surveillance be performed, the establishment has 30 days to respond to FDA with its plan. The plan, as a minimum, shall include (in accordance with §822.9):

“(a) Organizational/administrative information:

(1) Your name and address;

(2) Generic and trade names of your device;

(3) Name and address of the contact person for the submission;

(4) Premarket application/submission number and device identifiers for your device;

(5) Table of contents identifying the page numbers for each section of the submission;

(6) Description of the device (this may be incorporated by reference to the appropriate premarket application/submission);

(7) Product codes and a list of all relevant model numbers; and

(8) Indications for use and claims for the device;

(b) Post-market surveillance plan;

(c) Designated person information;

(1) Name, address, and telephone number; and

(2) Experience and qualifications.”

In accordance with §822.10, the plan (as a minimum) shall include:

(a) The plan objective(s) addressing the surveillance question(s) identified in our order;

(b) The subject of the study, e.g., patients, the device, animals;

(c) The variables and endpoints that will be used to answer the surveillance question, e.g., clinical parameters or outcomes;

(d) The surveillance approach or methodology to be used;

(e) Sample size and units of observation;

(f) The investigator agreement, if applicable;

(g) Sources of data, e.g., hospital records;

(h) The data collection plan and forms;

(i) The consent document, if applicable;

(j) Institutional Review Board information, if applicable;

(k) The patient follow-up plan, if applicable;

(l) The procedures for monitoring conduct and progress of the surveillance;

(m) An estimate of the duration of surveillance;

(n) All data analyses and statistical tests planned; and

(o) The content and timing of reports.

For those of you that think the post-market surveillance is a “one and done” scenario, hold your horses. According to FDA, the postmarket surveillance period can be 36 months, depending on the burning question/issue in which the agency is trying to obtain answers. In fact, the agency can exceed 36 months if they believe the nature of the question requires that much data to ascertain an appropriate answer and subsequent problem resolution.

Once the FDA receives an establishment’s plan, they will have 60 days to review and make the following decisions: Accept, reject or request revisions. Additionally, if an establishment disagrees with FDA’s decision with regards to the postmarket plan, the following options are available (once again, good luck from Dr. D):

1. Request a meeting with the Director, Office of Surveillance and Biometrics, CDRH
2. Seek and internal review of the postmarket surveillance order
3. Request an informal hearing
4. Request a review by the Medical Devices Dispute Resolution Panel of the Medical Devices Advisory Committee

For you Chief Jailable Officers (CJOs) out there that have a little bit of rebel in you, you can always throw caution to the wind and just ignore the entire process. Unfortunately, the FDA would view the establishment’s failure to submit the postmarket surveillance plan or complete the plan once approved, as a violation of Section 522 of the Act. At that point in time, the agency would undoubtedly unleash some serious regulatory pain. The FDA would consider the offending establishment’s product misbranded under the Act and do everything in their power to block misbranded devices from entering the market place. Can you say “product seizures”? Additionally, individuals such as the CJO can quickly become targets of prosecution for their willful and blatant disregard for the Act. Did the doctor mention the real possibility of fiscal penalties, a.k.a. fines? Some additional watch outs are:

• If an establishment decides to pull the subject device from commerce, the postmarket surveillance activities must continue. The establishment can request permission to terminate the activities from FDA.
• Device establishments are always free to request a waiver and/or an exemption from FDA, as it pertains to Part 822 (good luck with that).
• The establishment tasked with executing the post-market surveillance and their investigators shall retain their records for a minimum of two years upon acceptance of the final report by FDA.

Takeaways

For this week’s guidance, the doctor will leave the readers with just two takeaways. One: If the FDA issues an order for a postmarket surveillance, do not assume that it is similar to what your establishment is performing (routinely) for Europe—it is not. The FDA’s order will be for a specific device or device family, and will want a substantial amount of data so a decision can be made with regards to the ongoing safety and efficacy of the device in question. Two: Failure to respond to the FDA’s request for a postmarket surveillance will result in some serious regulatory pain for the offending establishment. In closing, thank you again for joining Dr. D, and I hope you find value in the guidance provided. Until the next installment of DG, cheers from Dr. D. and best wishes for continued professional success.

References

1. Code of Federal Regulation. (April 2015). Title 21 Part 820: Quality system regulation. Washington, D.C.: U.S. Government Printing Office.
2. Code of Federal Regulation. (April 2015). Title 21 Part 822: Post-market surveillance. Washington, D.C.: U.S. Government Printing Office.
3. Devine, C. (2011). Devine guidance for complying with the FDA’s quality system   regulation – 21 CFR, Part 820. Charleston, SC: Amazon.
4. Devine, C. (2013). Devine guidance for managing key attributes of a FDA-compliant quality management system – 21 CFR, Part 820 Compliance. Charleston, SC: Amazon.
5. FDA orders duodenoscope manufacturers to conduct postmarket surveillance studies in health care facilities. (October 2015). FDA News Release. Accessed October 12, 2015. Retrieved from http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm465639.htm