Thanks again to Rob Packard for providing another guest post. Rob is a Regulatory Affairs and Quality Management System expert whose specialty is helping companies with regulatory submission of a Design Dossiers for CE Marking of high-risk Class III medical devices. You can read more of Rob’s work at QC is Dead and RA Review blogs. 

Thank you for reading my previous posting on Creo Quality, “CE Marking Process for Medical Devices – A Step by Step Example” from August 14^th. This third posting in the series explains the process for obtaining US FDA Clearance for medium-risk Medical Devices.

For our example, we will be using the same hypothetical client for Jon to help.

Jon’s client called to say that they are now ready to tackle the US market. As with the Canadian and European markets, the US FDA considers cyanoacrylate a medical device when it is used as a topical adhesive. Jon’s first step is to determine the device classification. Jon’s client was considering asking the FDA to identify the classification of topical adhesives using the 513(g) submission process, but Jon had a free solution. Jon showed them my blog from September 11^th (http://wp.me/p19REq-8E)—which conveniently used another topical adhesive as an example.

The information provided in my earlier blog identifies topical adhesives as a Class 2 device with the three-letter product code “MPN”. This product classification also gives Jon’s client additional options that are not available to all companies that are trying to achieve 510(k) clearance for the first time. Most new products can only achieve initial 510(k) clearance from the US FDA by submitting a “traditional” 510(k). This process is supposed to take 90 days—assuming there are no significant questions about the submission and there are no backlogs with the reviewer.

For some products, there are recognized consensus standards (i.e. – ISO Standards) that define the performance requirements for a medical device or a Special Controls document published by the FDA that identifies which performance Standards the FDA requires for a specific product classification. In the case of topical adhesives, the FDA has published a Special Controls document. When there is a Special Controls guidance document available, the company may submit an “Abbreviated 510(k)” instead of a Traditional 510(k). An Abbreviated 510(k) contains summaries of all the testing results required in the Special Controls document or in an ISO Standard recognized by the US FDA. Since all the required performance testing presented in an Abbreviated 510(k) is in accordance with a previously accepted standard, the FDA reviewer only has to verify that the performance testing identified in the Special Controls document or the ISO Standard has been completed and acceptance criteria have been met. Therefore, the reviewer needs less time and clearance can be achieved in 60 days—instead of 90 days.

In addition to Special Controls documents, the FDA also has guidance documents for other things, such as: “Format for Traditional and Abbreviated 510(k)s.” By following this document verbatim, Jon can avoid a lot of time-consuming questions from a reviewer that is having trouble finding the information they are looking for. If a section of the suggested format is not applicable, Jon knows that he should still include this section. However, he should indicate the reason why this section is not applicable in a brief paragraph (i.e. – a one page section).

As Jon reads through the Special Controls Guidance document, he realizes that a specific format for Abbreviated 510(k)’s is described for topical adhesives. Therefore, Jon modifies his normal template to match the FDA format for topical adhesive Abbreviated 510(k)’s. As Jon reads further, he realizes that there will be some additional testing required that his client may not have anticipated.

In the Special Controls document, there are several risks and recommended mitigation measures identified:

The risks of adverse tissue reaction, chemical burns, and infection have all been addressed by biocompatibility testing and sterility testing. Jon’s client also performed animal testing to identify any problems in a simulated use environment. However, the client did not perform any testing to specifically address unintentional bonding, wound dehiscence, applicator malfunction or delayed polymerization. Some of these questions were asked and answered during the CE Marking application process, but the client did not have formal protocols and test reports to address these risks.

Another difference between testing that Jon’s client performed in the past and the US FDA’s requirements for a 510(k) submission is the concept of a predicate device. Jon’s client needs to select a similar topical adhesive that received a 510(k). Ideally, a recent 510(k) should be selected because “old” technology may no longer be considered acceptable from a safety standpoint. In the case of topical adhesives, the applicator is one of the primary differences between legacy products and more recent 510(k) products. The most recent version of Surgiseal™ (see picture below) is an example of a new applicator for a monomeric, 2-octyl cyanoacrylate similar to the product Jon’s client is selling in Canada and Europe.

Jon’s client has a similar applicator design to the pictures above, and therefore Surgiseal is selected as the predicate device for this hypothetical 510(k) submission. For all the testing protocols that need to be created for this 510(k) submission, comparative testing is performed with a sample of Surgiseal and a sample of product made by Jon’s client. In each of these protocols, the acceptance criteria is performance “not worse than Surgiseal”.

In addition to completing the testing required for the 510(k) submission, Jon’s client also needs to add procedures to their Quality System to address unique US FDA requirements. Jon’s client already has a training procedure, but the data analysis procedure does not address the requirement for statistical techniques in 21 CFR 820.250. There are also requirements for maintaining a device master record (21 CFR 820.181), medical device reporting (21 CFR 803) and corrections/removals (21 CFR 806).

Jon’s client completed all of the required testing protocols comparing their new product with Surgiseal™ within 10 weeks. During this same period, Jon helped them to update their procedures to meet the FDA’s specific requirements that are not included in Canadian or European legislation or the ISO 13485 Standard. Finally, Jon’s client was ready to pay their fee for the 510(k) submission and submit the 510(k) for review. The FDA reviewer requested copies of a few of the reports that were summarized in the submission: biocompatibility testing reports, sterilization validation reports, and a usability report that was created to address human factors concerns related applicator malfunction and use errors. Each of these reports were provided by email within 24 hours of the request. The reviewer had no further questions, and the 510(k) clearance letter was issued within 55 days of initial receipt.

After receipt of the 510(k) clearance letter, Jon’s client registered with the FDA as a device manufacturer and specifications developer and began selling in the USA.