Dr. Christopher Joseph Devine, President, Devine Guidance International
Devine Guidance

Refused Entry into the United States!

By Dr. Christopher Joseph Devine
Dr. Christopher Joseph Devine, President, Devine Guidance International

When adulterated products are manufactured in a foreign establishment, don’t expect FDA to admit them into the country.

Before the readers jump to any conclusion premised on the title, this week’s guidance is not about a certain caravan trekking through Central American and Mexico to gain entry into the United States; it is an article about adulterated products manufactured by a foreign establishment. For those readers not familiar with 21 CFR, Part 807 (Establishment registration and Device Listing for Manufacturers and Initial Importers of Devices); §807.81(a)(3)(i) requires a new 510(k) submission when significant changes are made to a device. For example, new device features, change in sterilization methods, or significant changes to product dimensions warrant a new submission. When in doubt, reach out to FDA and ask. Dr. D’s experience is they really do want to help device establishments make the correct choices. However, for device establishments that believe in throwing caution to the wind, bad things will eventually happen (no crystal ball is required). If you do not want to believe Dr. D, ask the chief jailable officer (CJO) tasked with helping the offending establishment mentioned in this week’s guidance navigate the often treacherous regulatory waters of FDA. Can you say refused entry? Can you say detention without physical examination? In his wayward youth, the doctor spent many a fine afternoon after school in detention. Detention was not a good thing many decades ago and the doctor guarantees that FDA detention is not going to be a pleasurable experience today. Hopefully, the CJO tasked with mitigating this issue and the other observations depicted in the prized agency warning letter is skilled in some level of deportment (look-it-up) to assist with the need to placate FDA during the entire warning letter mitigation process. Enjoy!

Warning Letter – July 2, 2018

Now granted, all warning letter observations should be considered serious and warrant mitigation activities as quickly as humanly possible. However, when the device establishment is on the receiving end of five Form 483 observations, they typically find themselves in a precarious position with our friends from FDA. Marry the multiple observations with claims of adulterated product, and that precarious position is usually in the agency’s doghouse. Not a fun place to be. The five observations noted in the agency pertained to:

  • One: Process validation (§820.75)
  • Two: CAPA (§820.100)
  • Three: Complaint management (§820.198)
  • Four: Measuring and monitoring equipment (§820.70)
  • Five: Device History Records (DHR)

Regardless of the nature of these observations, the one garnering substantial attention from FDA (a dedicated paragraph following all of the Form 483 observations) was the failure to file a new application for the significant design changes, ouch!

Warning Letter Excerpt(s)

“These devices are also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of the firm’s intent to introduce the devices into commercial distribution, in that notice or other information respecting modifications to these devices was not provided to FDA, as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 C.F.R. 807.81(a)(3)(i). Specifically, your firm has modified the Catheter Tip Pressure Transducer, cleared under K801757, by making the following changes:

• Addition of Sterrad sterilization method.

• Changes in the catheter’s lumen dimension and materials from 2.2 mm diameter, silicone rubber material to 7 mm diameter with a 6 Fr 2 mm diameter Polytetrafluoroethylene (PTFE) tube.

• K801757 is cleared for 1-4 sensors that will be placed along the length of the catheter; however, an addition of more than 4 sensors on the catheter per customer request is not included in the cleared 510(k).”

“Given the serious nature of the violations of the Act, the Catheter Tip Pressure Transducers manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify you regarding the adequacy of your firm’s responses and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.”

21 CFR, Part 807 – When a Premarket Notification is Required

“(i) A change or modification in the device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process.”

Compliance for Dummies

The doctor would like to reinforce the need to focus on correcting all of the Form 483 observations. That is what the FDA expects from device establishments, and the Federal Food, Drug, and Cosmetic Act (a.k.a. the Act) demands it. However, what constitutes a significant design change is a question for the ages, in Dr. D’s humble opinion. The doctor frequently fields questions on design changes, proposed product-line extensions, minor modifications and changes in the indications for use. The million-dollar question always being: Are we required to file a 510(k) (regular, special, or abbreviated) when design changes are made? The answer is always the same, it depends and not the adult diaper version: Depends (look-it-up). Seriously, if the change is relatively minor, such as changing the shade of a color for a catheter shaft (e.g., light-blue to dark-blue), or improving the tip-retention wire performance (increase in pull force due to a change in the wire gauge size), performing the appropriate level of testing and documenting the results in the design history file (DHF) is probably going to be acceptable. Increasing the width of a marker band to improve visibility under fluoroscopy is probably going to be acceptable too.

However, significant changes to the sterilization modality (e.g., EO to Gamma) are not going to be acceptable to FDA without a new 510(k). Adding more performance features, which result in new or revised indications for use, will not be acceptable to FDA without a new 510(k). Changes from Rx (requiring a prescription) to over-the-counter (OTC) use will not be acceptable to FDA without a new 510(k). As the doctor alluded to earlier in this week’s guidance, when in doubt, ask. Pick up the damn phone and call or send an email to the appropriate review group at FDA. The folks at CDRH and OCP are extremely responsive and will steer you in the right direction. To arbitrarily make a bad decision and tempt fate with the FDA is just not recommended. In fact, it would probably by safer walking (armed, of course) through the Southside of Chicago on a weekend evening. The doctor has taken the liberty of providing a useful link to FDA guidance for considering changes to products:



For this week’s guidance, the doctor will leave the readers with two takeaways. One: The FDA can and will use the refusal of entry (detention without examination) to prevent adulterated products from reaching the healthcare market in the United States. The agency’s number one job is to protect the health of individuals living within the borders of the United States. In fact, there is no tool greater, when attempting to drive compliant regulatory behavior, then shutting down the revenue stream of a device establishment that fails to play by the FDA’s rules. Remember folks, FDA owns the medical device regulatory sandbox in the United States, so FDA sets the rules (non-negotiable my dear readers) for establishments wanting to play in the sandbox. Two: When in doubt about the need to file a new 510(k) over a design change, please do not just wing it. If you are not sure, pick up the phone or send an email to the appropriate branch at FDA. You may not like the answer you receive, but it will be the correct one to follow. In closing, thank you again for joining Dr. D, and I hope you found value (and some humor) in the guidance provided. Until the next installment of DG, cheers from Dr. D., and best wishes for continued professional success.


  1. Code of Federal Regulation. (April 2018). Title 21 Part 807: Establishment registration and Device Listing for Manufacturers and Initial Importers of Devices. Washington, D.C.: U.S. Government Printing Office.
  2. Code of Federal Regulation. (April 2018). Title 21 Part 820: Quality system regulation. 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. (July 2018). Inspections, Compliance, Enforcement, and Criminal Investigations. Gaeltec Devices LTD. Accessed November 5, 2018. Retrieved from https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm624321.htm

About The Author

Dr. Christopher Joseph Devine, President, Devine Guidance International