January 14, 2020

High-level Overview of the 4 510(k) Guidance Documents for Premarket Notification by the FDA that Benefit Both FDA Reviewers and Device Sponsors

Author: Suzanne Broussard, PhD

The Premarket Notification 510(k) Program is the pathway used by manufacturers of low- to moderate-risk devices that are substantially equivalent (SE) to a device already on the market in order to begin the process of legally marketing in the United States. The Food and Drug Administration’s (FDA) release of 4 updated 510(k) guidance documents on September 13, 2019 was intended to both help streamline the FDA reviewer process and help sponsors save time and resources.  

The 510(k) Program is required for any device that does not need a Premarket Approval Application (PMA) and does not meet the specified exceptions. The sponsor must demonstrate that a device is at least as safe and effective, e.g. SE, to a legally marketed device that is not subject to PMA. The 510(k) submitters must receive a SE order from the FDA in order to market the device in the U.S. The SE determination typically takes 90 days, although that time is decreasing. Indeed, faster response times are one of FDA’s anticipated outcomes of these 4 guidance documents. The FDA hopes another outcome will be more guidance for the sponsors to streamline their submission process which will save time and resources. These outcomes are prevalent throughout the document and summarized in the FDA statement that 510(k) submissions “address the recommendations of an FDA guidance document should be easier to prepare by manufacturers and for FDA to review.” 

FDA Definition of a Legally Marketed Device 

Legally marketing a device based on a claim of substantially equivalent to devices legally marketed prior to May 28, 1976 (preamendments devices) requires the manufacturer to submit a Premarket Notification 510(k). The majority of premarket devices use the 510(k) program; hence, it is important to clarify FDA’s definition of a legally marketed device.  

A Legally Marketed Device must fit one of these 4 criteria: 

  • A Device that was legally marketed prior to May 28, 1976 (preadmendments device), or 
  • A device which has been reclassified from Class III to Class II or I 
  • A device which has been found SE through the 510(k) process 
  • A device that was granted marketing authorization via the De Novo classification process under section 513(f)(2) of the FD&C  

Note that the legally marketed device(s) used for equivalence is commonly referred to as the “predicate.”  

Here is a summary of the four 510(k) guidance documents FDA released to streamline the process and a bonus FDA webinar on Special 510(k)s. 

Refuse to Accept Policy for 510(k)s

The Refuse to Accept Policy for 510(k) Final Guidance Document contains nonbinding recommendations and supersedes the “Refuse to Accept Policy for 510(k)s” issued early in the same year (February 21, 2019). The newest Refuse to Accept (RTA) policy includes an early review that will inform the submitter within the first 15 calendar days after receipt of the 510(k) submission of issues against specific acceptance criteria with information as to the administrative completeness and if not, includes identification of missing element(s). This guidance includes checklists of which items a sponsor should include in their 510(k) submission if they want to ensure their application is reviewed in a timely fashion.  

Abbreviated 510(k) Program Final Guidance Document

The Abbreviated 510(k) Program is used by the FDA as an optional approach to the traditional 510(k) Program to demonstrate SE in premarket notifications by using guidance documents, special controls, and/or voluntary consensus standards to facilitate review of 510(k) submissions. This review relies on summary reports that “briefly describe and summarize the testing performed to support the submission as recommended in relevant guidance document(s).” 

Device manufacturers can choose the Abbreviated 510(k) pathway if the submission relies on one or more of the following: 

  • FDA guidance document 
  • Demonstration of compliance with special controls for the device type, either in a device-specific classification or a special controls guidance document; and/or 
  • Voluntary consensus standard(s) 

Format for Traditional and Abbreviated 510(k)s

The FDA provides specific guidance for the general framework of Traditional 510(k)s and Abbreviated 510(k)s in the Final Guidance Document. These formatting guidelines do not apply to Special or other premarket 510(k) submissions. FDA believes that using this Formatting Guidance will conserve both FDA and industry resources as well as facilitate timely 510(k) review. 

Special 510(k) Program

The Special 510(k) Program is designed to provide an optional and potentially expedited pathway to legally market “well-defined device modifications where a manufacturer modified its own legally marketed device and design control procedures produce reliable results that can form, in addition to other 510(k) content requirements, the basis for substantial equivalence (SE).” 

The Special 510(k) Program: Guidance for Industry and Food and Drug Administration Staff provides the FDA’s current thinking and intent on premarket notifications that are appropriate for review as a Special 510(k). This Final Guidance Document describes an optimal pathway for certain well-defined device modification for manufacturers that modify their own legally marketed device and clarifies the types of technological changes that are appropriate for review including changes to design, labeling, and indications for use. 


To further help clarify the Special 510(k) Program, the FDA recently held a webinar to discuss the Special 510(k) Program Final Guidance, and to answer questions. It is packed with useful information for those considering filing for the Special 510(k) Program including eligibility factors and examples of devices appropriate and those not appropriate for a Special 510(k). The recording of the webinar can be accessed here

Do you like it?0
December 17, 2019

What is the Role of the Quality Overall Summary (QOS) in BLA and NDA applications?

Author: Suzanne Broussard, PhD 

The Food and Drug Administration (FDA) is promoting the Quality Overall Summary (QOS) as a powerful tool to promote effective communication between regulators and sponsors of drugs as well as a tool that can substantially impact the efficiency and quality of the regulator’s assessment. The QOS is required for all New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs) and Biologics License Applications (BLAs), thus the QOS has significant potential to impact the regulatory review process for getting marketing approval. 

The QOS summarizes all quality-related information in the application. As part of Module 2 of the electronic Common Technical Document (eCTD), the QOS links to the sponsor’s larger body of data in Module 3. The QOS is expected to provide the regulator with sufficient information to understand the contents of Module 3 in a high-level overview. However, FDA suggests that many sponsors are falling short of these expectations and are not fully utilizing this powerful tool as an effective guide for regulators to assess the application.  

In order to help sponsors prepare a QOS that facilitates the regulators’ understanding of the product’s risks as outlined in the NDA, ANDA, or BLA applications, the FDA’s Office of Pharmaceutical Quality (OPQ) published a white paper that provides practical tips for putting the quality pieces together and explaining what regulators would like to see in the QOS: A Regulators Perspective on the Quality Overall Summary: Putting the Pieces Together.

The QOS provides the sponsor with an opportunity to summarize the key aspects of the new drug or biologics application, explain specific items for the regulators to consider, and extend to post-approval comments. Yet, a poorly written QOS requires regulators to spend significant effort to “understand, summarize, collate, and interpret quality data from module 3 (Figure 1).  

Figure 1. There can be a disconnect between applicants and regulators regarding the communication of quality data and its impact on the assessment. Currently, it takes time and/or communications (e.g., information requests) to fully understand the quality of data and its significance in an application.  

The FDA’s white paper describes key considerations for creating a highquality QOS to ensure regulators have a good idea of the potential risk to the patient and the control of this risk in the commercially manufactured product. The 3 key considerations are: 

  1. Identifying the main risks to the patient from a product quality perspective. 
  2. Understanding how the proposed overall control strategy controls and/or mitigates the identified failure modes of the manufacturing process or products.
  3. Acknowledging potential considerations for the quality assessment of the submission.

These key considerations are designed to help regulators evaluate the potential risks related to quality, and their potential impact on the patients, in a summarized benefit and risk assessment. Indeed, the FDA is encouraging sponsors to explain important aspects of the new drug or biologic such as how the product was formulated, and how the risk might impact the patients. Further clarifications on the 3 key considerations are provided in the FDA’s white paper.

Writing these technical documents to concisely convey information is challenging and you might want to consider these project management and quality control tips when putting you QOS together. These tips might just help improve your QOS, which will reduce the number of information requests from the FDA and thus decrease your NDA / BLA review time.

Do you like it?0
November 20, 2019

[FEATURED] It’s Raining Guidance Docs: FDA Expands Abbreviated 510(k) Program

In a new final guidance, the US agency has expanded its abbreviated 510(k) program for certain devices to look beyond conformity assessments and instead look at performance criteria. Alongside the guidance, the agency also released four draft guidances for devices it is considering clearing under the new pathway.

Do you like it?0
January 9, 2018

2018 – Good For The Device Industry, Good For Patients, Good For FDA

Read through an interview with Maureen Mulvihill of Actuated Medical, Inc. as she shares her educated predictions on her outlook for the medical device industry in 2018. She talks about funding, innovations, and the FDA as dynamics change this year.

Do you like it?0
October 12, 2017

Medical Device Single Audit Program: The Basics

Holding Globe in One Hand

Recently, the Regulatory Authority Council issued a report that the Medical Device Single Audit Program (MDSAP) has been successful in its pilot, and will therefore continue. So what is the MDSAP and why is it important? (more…)

Do you like it?0