A: Prior to the FDA Modernization Act of 1997 (FDAMA), all devices on the market as of May 28, 1976 were classified according to a risk based classification by FDA, working with Advisory panels. Any device that was not classified at that time is automatically assigned to Class III, requiring a premarket approval (PMA) application. A device could be moved out of Class III only through a cumbersome reclassification process.

FDAMA amended Section 513(f) to provide a new mechanism for reclassifying new Class III devices for which there is no predicate device. It allows the recipient of an NSE (not substantially equivalent) letter to request a risk-based classification determination to be made for the device. Program implemented in CBER & CDRH.

Both CDRH and the Center for Biologics Evaluation and Research (CBER) have implemented the De Novo process.

A: Use of the De Novo process could allow a company to submit a 510(k) for a new IVD that would otherwise have to get to market via the PMA process. The PMA application is longer and more complex than the 510(k) submission and its review and approval take additional time. The entire De Novo process can, of course, take considerable time. The 510(k) process may enable the company to get to market more rapidly. Also, the Post marketing phase for PMA products has more FDA oversight.

A: De Novo classification is intended to be used for lower risk IVDs for which no predicate device exists. If your new IVD is intended to diagnose a newly recognized serious desease, De Novo may not be the pathway for you. If, on the other hand, you have developed a new method of diagnosing a low risk condition, or if you have developed a test that is ancillary to other well-accepted methods, you may want to consider De Novo.

A: Sure, and it is the most important step in the process. ASK FDA!!! In fact, the best method both for determining whether De Novo may work ofr your product and for finding out how to proceed is to talk with the appropriate person in the Division of Clinical Laboratory Devices (DCLD), the branch chief that would review your 510(K) or PMA. If your device is reviewed by CBER, contact the Division of Blood Applications at 301-827-3524. De Novo decisions are typically worked out between FDA and the company in advance of the first submission.

A: Strictly speaking, no. The request for De Novo classification must be submitted to FDA within thirty (30) days of receipt of the NSE letter. The practical answer, though, is first to verify that your product was NSE'd for lack of predicate is to follow the advise above and get in touch with FDA or OBRR to find out whether your IVD is a candidate for De Novo. [sic] If so, you will have to submit another 510(k) and receive another NSE letter.

A: There are two reasons for submitting the 510(k). First, the law requires it. The Food, Drug and Cosmetic Act actually says a 510(k) must be submitted and an NSE letter issued before a company can officially request De Novo. Bear in mind that you should already have talked to the FDA about this possibility. The second reason is a practical one. In your initial discussions with FDA, the parties can determine what information will be needed to support a 510(k) for the IVD, as well as any other steps that may need to be taken (e.g. development of special controls, classification recommendation, etc.). If the information your company provides in the 510(k) is sufficient, FDA will be able to issue a classification order, allowing you to market your device, very promptly after the request for De Novo.

A: No. An "Unable to Determine" letter only tells your company that FDA did not have sufficient information about your IVD to make a decision. It is not the same as a final classification into Class III.

A: Yes, they have. FDA actually has used De Novo several times; for example, for Biotinylase, for a test for inflamatory bowel desease, for tissue culture media, and for HIV genotyping tests.

A: Non-existant. FDA cannot use the De Novo process to reclassify an IVD that is already in Class III. There is another process for reclassification.

A: FDA publishes all De Novo decisions in the Federal Register (See www.access.gpo.gov). It also appears in the CDRH 510(k) database (See www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm).

A: Probably not. A device that has been classified through the De Novo process can be used as a predicate device for future submissions. If you can demonstrate that your company's device is substantially equivalent to the device that has already been classified into class I or II through the De Novo process, you can simply submit a 510(k). If you are not sure whether the IVD you have under development could be found substantially equivalent, your best course of action is to call FDA.

A: The law specifies that FDA must make its decision within 60 days. Within 30 days of signing the classification order, FDA must publish the classification order. Ultimately, classification orders are published in the Federal Register. Bear in mind that if FDA requests any additional information either during the initial 510(k) review or during the review of the De Novo request, it must be provided within 30 days. Otherwise the device will remain in Class III.

A: The request should include:

• A cover sheet identifying the submission as "Request for Evaluation of Automatic Class III Designation"
• The 510(K) number on the NSE letter
• A statement of cross reference to the information in the 510(k)
• The classification recommended by the company (Class I or II)
• A risk/benefit analysis
• Discussion of the proposed general (Class I and II) and, if applicable special (Class II) controls that would be needed to assure safety and effectiveness of the device. Include whether the IVD should be exempt from or subject to 510(k) requirements, whether design control requirements should apply, and any special controls (e.g. voluntary standards) that would allow FDA to conclude that the IVD would reasonably likely be safe and effective for its intended use.
• Any test data not included in the 510(k) that are relevant to the request.

A: FDA's Center for Devices and Radiological Health published a guidance on February 19, 1998 entitled "New Section 513(f)(2)-Evaluation of Automatic Class III Designation, Guidance for Industry and Staff." This can be found on the CDRH website at www.fda.gov/cdrh/modact/classiii.html, or can be obtained through CDRH Facts on Demand at 1-800-899-0381, prompt 199.

A: For devices reviewed by CDRH, mail to: Document Mail Center (HFZ-401), Center for Deseases and Radiological Health, 9200 Corporate Boulevard, Rockville, MD 20850. For devices reviewed by CBER, send to the Document Control Center (HFN-99) 1401 Rockville Pike, Rockville, MD 20852-1448. Follow the usual procedures that have worked for your company for submitting 510(k) applications (e.g. Return Receipt Requested, overnight mail, etc.).

A: You have few options. Your company may simply submit a PMA for the IVD. The company also could submit a Product Development Protocol (PDP) in accordance with Section 515 of the FDCA. A third possibility is to submit a reclassification petition for the product, under Section 513 of the Act; see 21 CFR 860 for further information. Go up chain of command. Also, you can contact the CDRH Ombudsman Les Weinstein or the CBER Ombudsman Sherry Lard.

A: As noted above, be sure to talk to FDA prior to beginning the De Novo process. Make sure that you have mustered your best arguments in support of classification of your new IVD into Class I or II. If you believe that Class II is the appropriate classification for your new product and no guidance exists, you should consider preparing a guidance to precede your 510(k) submission, or to be submitted with your 510(k). This is another subject you will want to discuss with FDA.