Dr. D frequently sees device establishments default to the infamous and often problematic “Letter-to-File” when documenting their design changes versus taking the time and actually notifying FDA, as required in accordance with Part 807 requirements, or the filing of a PMA supplement in accordance with Part 814. Regardless, the FDA does have the authority to pursue regulatory action, including the issuance of a warning letter for entering a misbranded product into interstate commerce and the detention of products being shipped into the United States. For device establishments that fail to recognize when FDA notification of a design change is required, the Chief Jailable Officer (CJO) will be forced to offer a continuous stream of abject (look-it-up) apologies to the FDA. Enjoy!

Warning Letter –  December 11, 2015

Now granted, benign design changes that have zero impact on product safety and efficacy, and do not influence or modify the intended use of the device are probably candidates worthy of the letter-to-file approach. However, when additional operational modes are added for a previously cleared Class II device (K121719 – Part 890.5850) and the FDA is not notified of the changes, bad things will happen to the establishment that is entering the modified device into interstate commerce. Can you say warning letter? Can you say product detention? Can you say misbranded product? Can you say adulterated product? Seriously, the offending device establishment referenced in this week’s Devine Guidance (DG) received a warning letter in December 2015 for their failure to notify the FDA about significant design changes made to multiple products. In fact, the FDA also took issue with this establishment’s quality management system (QMS). Combine adulterated product with some quality system regulation compliance issues associated with the QMS, and the perfect storm begins to unload on this offending establishment. The doctor hopes the CJO has a really big umbrella.        

Warning Letter Excerpt

“During our inspection of your facility, your firm specifically identified K121719 as the applicable 510(k) clearance for your Elite Massagers.

1.   Our review of this 510(k) found your Elite Massager Multi-Pro is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g) for the device as described and marketed. The device is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because you introduced or delivered into interstate commerce for commercial distribution a device with major changes/modification to the intended use without submitting a new premarket notification to the agency, as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 CFR 807.81(a)(3)(ii).

Specifically, you have modified the Elite Massager Multi-Pro, cleared under K121719, by increasing the “massage modes” to eight. The device cleared under K121719 only has “six operation modes.”  The change in the number of operational modes constitutes a major change or modification to the device’s intended use, for which you lack clearance and approval.”

21 CFR, Part 820.30 – Design Controls

“(i) Design changes. Each manufacturer shall establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation.”

21 CFR, Part 807.81 – When a Premarket Notification Submission is Required

“(3) The device is one that the person currently has in commercial distribution or is reintroducing into commercial distribution, but that is about to be significantly changed or modified in design, components, method of manufacture, or intended use. The following constitute significant changes or modifications that require a premarket notification:

(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.

(ii) A major change or modification in the intended use of the device.”

Compliance for Dummies

Let Dr. D begin by emphatically stating, “the doctor cannot tell the readers what constitutes a significant design change.” That decision must be placed squarely on the shoulders of the R&D, quality, and regulatory personnel in each of your establishments. However, please keep in mind that these decisions are premised on a whole bunch of common sense. For example, if the indications for intended use changes or is expanded, then Part 807 becomes quite relevant. For example, if a urinary drainage catheter, designed for the adult population, has an expanded indication for pediatric use, you just might want to consider filing a new 510(k) for the expanded indication for use. However, if a circuit is redesigned due to the lack of continued availability of electronic components for an RF generator and the change has no impact on the performance of the finished device, then a letter-to-file placed in the Design History File (DHF) is probably going to be appropriate.

Regardless, the FDA expects device establishments to pursue specific steps when a design change occurs. Elements the agency expects to see for all design changes include:

• All design changes must be clearly identified and documented, regardless of how benign a design change appears to be
• Depending upon the design change, the change shall be appropriately validated and/or verified (test, test, and test again, if necessary)
• Prior to implementation, all design changes shall be adequately reviewed and approved
• Depending on the design change, FDA review and approval may be warranted either by 510(k) or PMA

As Dr. D has mentioned on many occasions, adherence with regulatory and statutory requirements mandated by FDA does not take a rocket scientist. However, it really does take some common sense, and frankly common sense is a trait that is missing for some CJOs.

Takeaways

For this week’s guidance, Dr. D will leave the readers with just one takeaway. If a design change is forthcoming to one of your establishment’s finished medical devices, please apply a little bit of common sense when it comes to notifying FDA. If the design change impacts form, fit, or function and/or the intended use of the finished device is changing or being expanded, then rest-assured, the agency is going to want to know about it. Please do not be that establishment that receives a warning letter because of design changes not being cleared or approved by FDA. 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 807: Establishment registration and device listing for manufacturers and initial importers of devices. 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. (December 2015). Inspections, Compliance, Enforcement, and Criminal Investigations. Elite Massagers, LLC. Accessed February 8, 2016. Retrieved from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm477579.htm