Recently, the U.S. Food and Drug Administration (FDA) issued final guidance on deciding when to submit a new 510(k) premarket notification application for a change to an existing medical device.1 The guidance is far reaching and will apply to all device manufacturers who intend to make changes to their devices going forward. The guidance covers changes made to devices that involve: (i) improvement in performance and safety; (ii) updated labeling; and (iii) switching to new materials. In fact, frequent changes to medical devices are the hallmark of the iterative process in the medical device industry.
Deciding whether to submit a new 510(k) after making changes to an existing device is critical to medical device manufacturers. On the one hand, submitting and obtaining clearance for a new 510(k) can be costly, complicated, and time-consuming.2 On the other hand, lacking a new 510(k) premarket clearance for a changed medical device may lead to recalls by the FDA3 and civil or criminal prosecution by the U.S. Department of Justice (DOJ).4
The 2017 Guidance
The FDA's 2017 guidance, which runs 77 pages, comprises several sections:5 guiding principles; flowcharts to assist the decision-making process and accompanying explanation; examples of the decision-making process; and documentation required by regulations. In this WSGR Alert, we highlight a few important aspects of the 2017 guidance.
Guiding Principles
The 2017 guidance specifies ten guiding principles that manufacturers should consider when deciding whether to submit a new 510(k) or to document changes made in accordance with device Quality System Regulations.6 First, the FDA notes that changes made with the intent to significantly affect safety or effectiveness of a device will likely require the submission of a new 510(k).7 Changes that are not intended to significantly affect the safety or effectiveness of a device should also be evaluated to determine their effect on safety or effectiveness.8 To complete the evaluation process for any changes made to a device, the manufacturer should conduct an initial risk-based assessment to identify and analyze both new risks and modifications to existing risks.9 Even unintended consequences of changes to the device should be considered in the risk-based assessment.10 The FDA defines a new risk as "a new hazard or hazardous situation that do not exist for the original device," and a significantly modified existing risk as changes in "the risk score, risk acceptability category, or duration of risk."11 After the initial risk-assessment, the manufacturer should routinely verify and validate its original evaluation of the impact on safety and effectiveness caused by the changes to the device, regardless of whether a new 510(k) has been submitted.12 If routine verification and validation produces unexpected results, the FDA notes that 'any prior decision that submission of a new 510(k) is not required should be reconsidered." Further, when evaluating many simultaneous changes, the FDA suggests that the changes should be assessed individually and in the aggregate.13 Finally, the FDA recommends that if multiple changes are made and only one change triggers the submission of a new 510(k), those changes not triggering a new 510(k) submission 'may be immediately implemented, so long as those changes can be implemented independently of changes that do require submission of a new 510(k)."14
Flowcharts and Accompanying Clarifications
To help manufacturers decide whether to submit a new 510(k), the 2017 guidance provides several flowcharts describing the decision-making processes for changes to: labeling; technology, engineering, and performance (for non-in vitro diagnostic devices); materials (for non-in vitro diagnostic devices); and technology, engineering, performance, and materials for in vitro diagnostic devices (IVDs); and considerations for risk-based assessments of modified devices. Each flowchart has endpoints of either: 1) to submit a new 510(k); or 2) to document the basis for not submitting a new 510(k). Also, each flowchart is accompanied by text that explains how to make a decision at each decision point.
Examples
To further illustrate the thought process behind each flowchart in the 2017 guidance, the FDA provides 32 examples answering the question of whether to submit a new 510(k) for many different types of changes.15 The examples are divided into groups involving changes for: labeling, design, materials, IVD technology, engineering, performance, and materials. Each example refers back to the corresponding flowchart and explains how a conclusion is made at each relevant decision point.
Documentation of a Decision Not to File a New 510(k)
As in the past, the FDA recommends that if a new 510(k) submission is not required based on the risk-based assessment, the manufacturer should document the decision-making process and the basis for that conclusion. The documentation should allow an FDA investigator or a third party to understand the nature of the changes made and the rationale supporting the conclusion not to file.16 The 2017 Guidance also provides key requirements for the documentation and examples of regulatory change assessment forms to demonstrate documentation principles.
Conclusion
The FDA's 2017 guidance is far reaching and will significantly impact all device manufactures going forward. As such, it is important for all device companies to be familiar with the new guidance and to revise existing standard operating procedures to reflect the new expectations of the FDA when changes are made to devices.
