Devine Guidance

Class III Devices

 

Can you say Pre-market Approval (PMA)? Good for you, but do you know what the PMA process entails? If so, golf clap and a hearty “good for you.” You can read this week’s guidance for its entertainment value.

For those readers wishing to learn just a tad-bit more about the FDA’s PMA process; please continue with the reading of this week’s guidance. Dr. D will attempt to teach, enlighten, and hopefully entertain you in the process. If your chief Jailable officer (CJO) believes that short-cuts are always available when pursuing a PMA, the doctor just purchased the new eastern span of the Bay Bridge and would like to sell it. The doctor will be the first one to tell colleges that FDA’s approval process for Class III device can be perceived as a “sinuous” (look-it-up) path. This is especially true if FDA has concerns over the pallet full of data an organization has submitted as their PMA.

Similar to Class I and Class II device, device manufacturers are required to register with FDA as an establishment in accordance with 21 CFR, Part 807; and all Class III devices are required to be listed in the FDA User and Registration Listing System (FURLS). However, the regulatory pathway for a Class III device is considerably more precarious. For starters, Dr. D recommends that you read 21 CFR, Part 814 as this document will dive into the PMA application process and shed light on FDA’s responsibility under the regulation. Class III devices are considered high risk devices. 

The agency’s PMA process is a scientific and regulatory process designed to review the safety and efficacy of Class III medical devices. This is real rocket science, right? According to FDA; 

 

 

The regulations allow for FDA to take 180-days for the PMA review process. Remember the bridge Dr. D has for sale, well if you believe the 180-day review process is a realistic timeframe, the doctor is also selling the Brooklyn Bridge too! Dr. D believes you should allocate at least 12 months for the agency’s review process. Yes, the sales and marketing folks are going to scream about time to market, but hey we are talking about Class III devices and not tongue suppressors.

As for the PMA application process, it is strongly recommend that you confer with the agency in advance. Number one, FDA will be better prepared to commence with the PMA review process associated with your organization’s submission; and number two, it will set the initial expectations in regards to the review process. Section 814.20 delineates the PMA application process. As a minimum, the application will need to contain (as applicable):

• Applicant name and address;
• Table of contents;
• Product summary containing: (a) indications for use; (b) device description; (c) alternative practices and procedures; (d) marketing history; (e) summary of clinical and non-clinical studies; and (f) conclusions drawn from the studies.
• A detailed description of: (a) device; (b) functional components/ingredients; (c) device properties; (d) theory of operation; and (e) manufacturing methods;
• References to claimed standards;
• Technical sections including: (a) results of nonclinical laboratory testing; (b) biological compatibility testing; (c) aging studies; (d) package testing, etc.
• Compliance statement for studies stating that the studies were performed in accordance with Part 812 or Part 813 (for example);
• Rationale for when clinical data comes from just one investigation site;
• Bibliography of published reports;
• Samples of the device, if requested by FDA;
• Copies of proposed device labeling;
• Environmental assessment;
• Financial certification and disclosure statement;
• Other information requested by FDA; and finally,
• Do not forget to sign the application!

Please remember that patience truly is a virtue when navigating FDA’s PMA process. Chances are good that there will be questions coming from FDA. In fact, expect a boatload of questions. If the clinical trials were mismanaged or the clinical data requires too much manipulation to support product safety and efficacy, i.e., too much time spending trying to normalize the statistical data sets; then expect a long and “arduous” (look-it-up) path.

Finally, did the doctor mention that the review fees for PMAs are not cheap? For FY 2013 the fee for a PMA is $248,000 ($62,000 for small businesses with revenue less than $100 million). Folks, the price tag alone should be reason enough to ensure the PMA is bullet proof prior to submitting the pallet full of documentation to FDA.  

For this week’s guidance the doctor will provide the readers with just one takeaway, be meticulous and thorough in the preparation of the PMA. FDA considers PMA devices high risk, and as such, expect an entirely new level of detail versus the 510(k) process. Make sure all of the supporting data, reports, written rational etc. are included as part of the submission process; and make sure there is just one point of contact to interface with 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. (2013, April) Title 21 Part 807: Establishment registration and device listing for manufacturers and initial importers of devices. Washington, 
2. D.C.: U.S. Government Printing Office.
3. Code of Federal Regulation. (2013, April). Title 21 Part 814: Premarket approval of medical devices. Washington, D.C.: U. S. Government Printing Office
4. Code of Federal Regulation. (2013, April). Title 21 Part 820: Quality system regulation.  Washington, D.C.: U. S. Government Printing Office.
5. Devine, C. (2011). Devine guidance for complying with the FDA’s quality system regulation – 21 CFR, Part 820. Charleston, SC: Amazon.