FDA Seeks 21st Century Agility with 510(k)s

Working with the Premarket Notification, also known as the 510(k) process, since 1978 has allowed me to view the big picture of definitive ups and downs in the challenging device submission process. Over the last 15 years, the regulatory landscape has changed from a standpoint of FDA and industry expectations, submission efficiency, user fees, complexity, guidance document creation, risk-based decision-making and FDA interaction.

I recall the 1980s Agency-wide initiative to reduce the amount of time it took to trudge through the submission process. Many 510(k)s took over a year from start to finish. Then in the 1990s and into the early 2000s, rapid fire results became in vogue in D.C. I can remember successfully filing a submission that took 28 days. I’ll never forget it. Conversely, I want to forget the one that took more than 328 days.

In this article, I will outline new initiatives by FDA to streamline the occasionally cumbersome 510(k) submission process. The “new FDA” seeks an innovative agility that includes greater accuracy, proper documentation without encumbrances, foundations built on science and engineering, formal guidance documents, risk aversion decisions and, yes, a more interactive FDA.

Background Information: FDA Develops a Tiered System
A person or company that intends to introduce a device into commercial distribution is required to first submit a 510(k) to FDA. FDA may issue an order of substantial equivalence once it has determined that the device meets requirements that prove it is as safe and effective as a legally marketed device. In order to ensure Premarket Notification requirements are met, the Agency developed a tiered system that allocates more of its review resources to high risk devices. Under this tiered system, substantial equivalence determination for low risk devices is based primarily on descriptive information and a review of the label, while the decision for higher risk devices considers performance data.

FDA Lightens its Self-imposed Burden, Exempting Class I Devices
To optimally manage workload and allocate resources, FDA exempted Class I devices for which it determined that Premarket Notification requirements were not needed to provide reasonable assurance of safety and effectiveness.

Between the passage of the Medical Device Amendments of 1976 and the Food and Drug Administration Modernization Act (FDAMA) in 1997, FDA exempted 574 generic types of Class I devices from Premarket Notification. As a result, Class I devices are exempt from Premarket Notification requirements, unless the device meets “reserved” criteria, meaning it is intended for a use that is of substantial importance in preventing impairment to human health or presents a potential unreasonable risk of illness or injury.

The passing of FDAMA also gave FDA the authority to exempt certain Class II devices rather than down-classifying them to Class I before they become eligible for exemption. FDA has noted that additional Class II devices may become exempt from Premarket Notification in the future.

The Agency’s last step in evaluating devices subject to 510(k) review involves pre-amendments Class III devices. FDA plans to down-classify pre-amendment Class III devices for which general controls or special controls are sufficient to ensure safety and effectiveness to either Class I (510(k) exempt or reserved) or to Class II. The remaining Class III devices will be subject to either Premarket Approval (PMA) or product development protocol (PDP) requirements.

Continue reading about the
FDA approval process:

FDA Clarifies Substantial Equivalence Requirements for 510(k) Submissions

The Starting Line: Turning the Corner with a Device Concept  

The New 510(k) Paradigm
The Agency has developed “The New 510(k) Paradigm” to streamline the evaluation of Premarket Notifications for the reserved Class I devices, Class II devices subject to Premarket Notification and pre-amendments Class III devices for which FDA has not yet called for PMAs. The paradigm presents device manufacturers with two approaches for obtaining 510(k) clearance. While the new paradigm maintains the traditional method of demonstrating substantial equivalence, it also presents the “Special 510(k): Device Modification” option, which utilizes the Quality System Regulation, and the “Abbreviated 510(k)” option, which relies on usage of guidance documents, special controls and recognized standards to facilitate 510(k) review. Use of these alternatives does not affect FDA’s ability to obtain information authorized by the statute or regulations.

Special 510(k): Device Modification: Under this alternative, a manufacturer intending to modify their own legally marketed device will conduct the risk analysis and the necessary verification and validation to demonstrate that the design outputs of the modified device meet the design input requirements. Upon completion of this process, a “Special 510(k): Device Modification” can be submitted. The basic content requirements of the 510(k) remain the same, and the cleared 510(k) number and a “Declaration of Conformity” with design control requirements are both added.

Device manufacturers may choose to submit an Abbreviated 510(k) when:

  • a guidance document exists
  • a special control has been established
  • FDA has recognized a relevant consensus standard

An Abbreviated 510(k) submission must include the required elements identified by FDA in 21 CFR 807.87. When a manufacturer submits an Abbreviated 510(k) that relies on a guidance document and/or special controls, it should include a summary report that describes how the guidance document and/or special controls were used during device development and testing. The summary report should define the manufacturer’s efforts to conform to the guidance document and/or special controls and should outline deviations. Manufacturers submitting an Abbreviated 510(k) that relies on a recognized standard should provide the required information described in the standard and a statement of conformity to the recognized standard. More information can be found in the Agency’s document, “Guidance on the Recognition and Use of Consensus Standards.”

FDA has incentivized manufacturers by expediting the review of their submissions when they provide summary reports on the use of guidance documents and/or special controls or declaration of conformity to recognized standards. While FDA has acknowledged that abbreviated submissions will compete with traditional 510(k) submissions, it is anticipated that the Abbreviated 510(k) review will be more efficient than that of traditional submissions, which are often data intensive. Also, by allowing Office of Device Evaluation reviewers to rely on a manufacturer’s summary report, review resources can be directed toward more complicated issues, thus expediting the process.

Improvements Using Guidance Documents
FDA’s guidance documents do not establish legally enforceable responsibilities, but provide the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The Agency uses the word should when something is recommended, but not required. Several recent 510(k)-aligned guidance documents that may interest orthopaedic device manufacturers follow.

Computational Modeling and Simulation (CM&S) Studies – CM&S studies have been used to support device submissions for years, specifically in the areas of solid mechanics (e.g., maximum stress locations in a hip implant), and other disciplines (modalities such as fluid dynamics and mass transport, electromagnetics and optics, ultrasound and heat transfer). FDA provides recommendations on the formatting, organization and content of CM&S study reports used as valid scientific evidence to support device submissions. The guidance also helps FDA staff improve the consistency and predictability of the studies’ reviews.

Specific details need to be included in CM&S study reports in order to provide valid scientific evidence for regulatory submission. In the new guidance, the term “CM&S report” refers to the portion of a premarket submission that provides information about a CM&S study; it does not describe a new submission requirement. With this document, FDA aims to establish uniformity in reporting CM&S studies, as the Agency recognizes that there is a variety of CM&S modalities and specific details will vary across medical disciplines.

Custom Device Exemptions (DRAFT) - FDA developed this document to provide guidance about implementation of the custom device exemption contained in Section 520(b) the Act. The new provision amended an existing custom device exemption and introduced new concepts and procedures for custom devices, such as:

  • devices created or modified in order to comply with the order of an individual physician
  • the potential for multiple units of a device type (not to exceed 5 units per year)
  • qualifying for the custom device exemption
  • annual reporting requirements by the manufacturer to FDA about devices manufactured and distributed under the Act

Modifications to a 510(k)-cleared device that maintains the original intended use and could be clinically studied are not considered appropriate as a custom device. However, if an existing 510(k)-cleared device is modified in order to treat a unique pathology or unique physiological condition, rendering it incapable of clinical study, the device could potentially qualify as a custom device. There are options.

Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications with Different Technological Characteristics (DRAFT) – FDA developed this guidance to improve the predictability, consistency and transparency of the 510(k) premarket review process. As previously mentioned, a submitter of a Premarket Notification submission must demonstrate to FDA that the new device is “substantially equivalent” (SE) to a legally marketed (predicate) device. At certain points in the analysis, the probable benefits and risks of a new device as compared to a predicate device may be relevant. This guidance helps submitters of 510(k) Premarket Notifications demonstrate substantial equivalence in their premarket submissions. The guidance does not change the 510(k) premarket review standard or ask the submitter of a 510(k) to provide additional performance data from what has traditionally been submitted during the review process.

Industry and Food and Drug Administration Staff- Applying Human Factors and Usability Engineering to Optimize Medical Device Design (DRAFT) – This document was developed to assist industry in conducting appropriate human factors testing and identifying device features that manufacturers should optimize throughout the total product life cycle. This guidance provides recommendations for device design optimization through human factors analysis, testing and validation. The intent of the guidance document is to improve the quality of the device user interface such that errors that occur during use of the device are eliminated or reduced.

Manufacturers conduct a risk analysis that includes risks associated with device use as part of their design controls. If the analysis results in indication that there is a moderate to high risk of user error or if a manufacturer is modifying a marketed device due to problems associated with use, then the manufacturer should perform human factors testing according to this guidance document. FDA may also request human factors testing if the:

  • submission of human factors information is required
  • submission of human factors information is recommended in a specific guidance for a device type and the manufacturer cannot justify forgoing such testing
  • for-cause basis is the least burdensome method to address FDA’s concerns regarding human factors issues

Under these circumstances, manufacturers should provide FDA with a report that summarizes the human factors processes, evaluations and results of validation testing as part of their pre-market submissions.

Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile – FDA believes that using novel non-traditional sterilization technologies carries a substantial risk of inadequate sterility assurance that could lead to devices not complying with GMP. Failure to assure sterility presents a serious risk to human health due to the possibility of infection. Therefore, FDA intends to inspect the manufacturing facility before clearing a 510(k) for a device that is sterilized by a novel non-traditional sterilization process. Examples of traditional sterilization methods are: dry heat, ethylene oxide (EtO) with devices in a fixed chamber, moist heat or steam, radiation (e.g., gamma, electron beam). Examples of non-traditional sterilization methods are hydrogen peroxide, gas plasma or ozone. Novel non-traditional sterilization methods include chlorine dioxide, ethylene oxide-in-a-bag, high intensity light or pulse light, microwave radiation, sound waves, ultraviolet light or vaporized chemical sterilant systems (e.g., hydrogen peroxide or peracetic acid).

Concluding Statements
There are more guidance documents in place for industry and FDA to use for consistency and up-to-date decision-making. As experience is gained by industry and FDA, guidance documents may be updated and revised with a streamlined process—a modern and confident agility, if you will. Guidance documents have made a positive and worthwhile difference moving forward; that is, the principles presented in guidance documents can be implemented through changes in the administrative processes and do not require changes to either the Premarket Notification regulation or to the Act. Information management and changes are now on the fast track.

FDA’s Center for Devices and Radiological Health (CDRH) has recently issued the final version of the guidance, “510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications.” This guidance document is intended to help make the existing regulatory framework, policies and practices easier to understand, i.e. to improve the predictability, consistency and transparency of the 510(k) premarket review process. This will help to assure that patients get timely access to new, safe and effective devices.

The final guidance clarifies each of the critical decision points used during the 510(k) review process and replaces the K86-3 Blue Book Memorandum, “Guidance on the CDRH Premarket Notification Review Program, 510(k).” It is important to note that this guidance does NOT alter the substantial equivalence standard or data requirements. Instead, it specifies information that manufacturers should include in product submissions, explains when clinical data may be required and provides an easy to follow decision-making flowchart to help manufacturers through the application process. This final guidance does not address FDA’s Special and Abbreviated 510(k) programs, as FDA intends to finalize those sections separately.

FDA is changing, and so are the approaches to industry submissions. The new FDA seems to be more informed and has taken the necessary steps to use risk management practices to paint a regulatory scene using science and engineering as foundational points of order. It is rather refreshing to know that the basis for judging the content of a 510(k) isn‘t steeped in opinion, as it sometimes was in the past. There is usually a firm technical foundation at CDRH these days for making decisions and consequently the 510(k) process and the outputs have greater credibility and a certain consistency you can depend on. FDA believes that the new approaches to Premarket Notifications will make a difference, and so do I.

John Gagliardi has had success over the past 40+ years in the Medical Device and Pharmaceutical industries because of his practical approach to process-orientation and business. He has been actively involved in research and development, quality assurance, training, operations, process architecture, FDA inspections and regulatory affairs. John specializes in building systems in a compliant and business-ready manner. John can be reached at This email address is being protected from spambots. You need JavaScript enabled to view it..

MidWest Process Innovation, LLC