SUBSTANTIAL EQUIVALENCE - PREMARKET NOTIFICATION, 510(K)

If a your device has equivalent materials, performance and uses to a previously approved product, you may be able to bypass many of the hurdles posed by the PMA by filing what is referred to as Premarket Notification for the equivalent part.

The term five-ten-K is derived from section 510(k) of the FDC Act and is another way of referring to an application for Substantial Equivalence or Premarket Notification. All three terms indicate an attempt to demonstrate that a newly introduced device is so similar to a predicate device (an already legally marketed device to which you claim equivalence) that the PMA process or other special controls are not necessary to show safety and efficacy. A substantially equivalent device is defined as:

A device that has the same intended use as a predicate device, does not raise different questions of safety and effectiveness, and has either the same technological characteristics as the predicate device or has different technological characteristics but demonstrates it is as safe and effective as a predicate device.

Any establishment wanting to market a device intended for human use in the U.S. will most likely have to, at the very least, submit a 510(k). Any change to the device's intended use or any significant change or modification made to a predicate device that may affect safety or efficacy will require premarket notification no later than 90 days before marketing.

There is no specific 510(k) form to be filled out. The application must be constructed and submitted according to specific formats (see CDER website for information on the 510(k) Submission Process links to Title 21 of CFR 807). You will have to include various types of data to establish your device as substantially equivalent and otherwise support that claim. Additionally, a summary and citation of all adverse safety and effectiveness data related to both your device and the predicate device must be included.

Most significantly, if a company successfully applies for Class III premarket notification, they may forgo the rigors and expenses of a PMA. The 510(k) only costs about $2000 and is worth the expense if there is any chance that any part of your device might gain equivalence status.

The CDRH has recently introduced a New 510(k) paradigm that presents device manufacturers with two additional optional approaches for obtaining market clearance. The Special 510(k) Device Modification option utilizes certain aspects of the Quality System Regulation (formally known as GMP), while the Abbreviated 510(k) option relies on the use of guidance documents, special controls, and recognized standards to facilitate 510(k) review.

SPECIAL 510(K): DEVICE MODIFICATION

The Special 510(k) may offer a less burdensome option than the standard 510(k) application and the Office of Device Evaluation (ODE) will be processing the Special 510(k) within 30 days of receipt.

There is a common understanding as to what types of device modifications may be made through a Special 510(k) application. Where evaluation is intended to ensure the modified device continues to meet user requirements as opposed to patient safety and effectiveness the Special 510(k) will likely be the appropriate and preferable avenue.

Modifications to predicate devices that do not affect a device's intended use or alter its fundamental scientific technology should usually qualify for the Special 510(k), or 30-day change as it is often referred. Such modifications might include:

1. Changes to formulation or type of material used
2. Energy type
3. Dimensional specifications
4. Software or firmware
5. Packaging or expiration dating
6. Sterilization

The Special 510(k) relies more heavily on quality system regulations (or GMPs) to ensure safety and effectiveness than does the standard application. To utilize it, manufacturers must have a systematic set of requirements and operating procedures for design and development that can act independently to ensure safety and efficacy.

Note that if a clinical investigation is necessary to answer safety and effectiveness questions relating to a particular modification, a Special 510(k) will not likely be the appropriate avenue.

ABBREVIATED 510(K)

This option allows for the streamlining of substantial equivalence review. It can be utilized by manufacturers when device-specific guidance documents exist, a special control has been established by the FDA, or when the FDA has recognized a relevant consensus standard.

The CDRH is developing device-specific guidance documents to identify device information that might standardize certain types of marketing authorizations. You may be able to reduce 510(k) review time by submitting a summary report outlining your adherence to the guidance documents.

As in the case of guidance documents, summary information that describes how special controls (as described under the Medical Device Classification, Class II section) have been used to address a specific risk should also reduce the time and effort to prepare and review 510(k)s.

In addition, the CDRH is developing individual consensus standards. The Modernization Act authorizes them to recognize all or part of national or international standards through publication of a notice in the Federal Register. Recognized standards could be cited in guidance documents or individual policy statements, or established as special controls (as described in the Medical Device Classification section) that address specific risks associated with a type of device. Certain aspects of a medical device might be broadly applicable and if a standard is approved for such applications and combined with modified review procedures, the FDA should be able to streamline the review of 510(k)s covered by the standard. To learn about qualifying for such a standard, see Consensus Standards Database.

EXEMPTIONS

A 510(k)/GMP Exemption gives an establishment the legal right to manufacture and distribute a device to the public without going through the approval application process, while an Investigational Device Exemption permits use of an unproven device for clinical studies. These are the two primary types of exemptions.

510(K)/GMP EXEMPTIONS

The 510(k) exemption applies to almost all Class I devices. These devices are identified and listed as exempt from FDA marketing approval and often times from quality systems regulations (GMPs) as well. However, they are still subject to various appropriate general controls, applied individually as deemed necessary by the CDRH.

The FDA has also published a list of Class II devices, subject to certain limitations, that are now exempt from marketing approval by the FDA prior to distribution. If you think there is a chance you might get on that list, you may want to contact your regulatory attorney. See Appendix of Links for web site to exemptions and list of exempt Class II devices.

Note: When dealing with one of these devices you must still file for the exemption. You will, however, be saved the substantial costs of premarket approval or recognized substantial equivalence. Also, Class II devices are never exempt from GMP requirements and are still subject to other general and special controls.

INVESTIGATIONAL DEVICE EXEMPTION (IDE)

An Investigational Device Exemption (IDE) allows a device to be used in clinical studies to collect the safety and effectiveness data required to support a marketing application. Although the term exemption might often indicate a reduced workload, getting an IDE is, to the contrary, an involved process. Even after receiving approval to move forward, compliance with IDE regulations will continually demand your attention and keeping the Institutional Review Board satisfied can be a nagging responsibility.

Table 3. Medical Device 2003 Regulatory Filing Fees for Small Businesses

An Institutional Review Board (IRB) is an impartial board of at least five respected citizens of diverse backgrounds that act as watchdogs for the rights of patients participating in investigations or studies. The IRB is necessary for the approval of almost any study. They are primarily responsible for:

• Approval of the written protocols for treatment and data collection.
• Guarding against financial and other conflicts of interest;
• Categorizing your device as a Significant Risk study or a Non-Significant Risk study; and
• Assuring that fully informed consent is given by each participant.

The IDE regulations differentiate between Significant Risk (SR) and Non-Significant Risk (NSR) devices. Only the SR devices require submission of an entire IDE Application. For NSR devices the CDRH calls for only an abbreviated version of the IDE. If the device investigation is designated as NSR, the investigation may begin immediately at the institution represented by the approving IRB. In case of an SR designation, both the IRB and FDA must approve all parts of the exemption application before the trial may begin. An SR device is defined as one that:

• Is an implant
• Is used in supporting or sustaining human life
• Is of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise preventing impairment of human health; or
• That otherwise presents a potential for serious risk to the health, safety or welfare of a subject

An NSR device is one that does not meet the SR definition. The FDA website offers further guidance on SR vs. NSR designation.