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This article explores key elements of FDA's final guidance to the medical device industry for deciding when to submit a new 510(k) for medical device hardware and software design changes issued 25 October 2017. The author assesses the potential business impact and suggests what companies need to do to align with FDA's final guidance.
In response to technological advancements, broadening medical knowledge and clinical use, medical device designs frequently evolve over time and the designs come in many forms. Design changes are often in response to industry pressures for increased customer satisfaction and device safety, maximized performance, manufacturability, and to achieve cost efficiencies.
Regulatory professionals within the medical device industry have many roles—one of which is the impact assessment of proposed design and labeling changes on medical devices that have previously received marketing clearance from the US Food and Drug Administration (FDA) or a pre-amendment to a device that is subject to 510(k) requirements. A new premarket notification (510(k) filing) on a medical device is required for "a significantly changed or modified design, components, method of manufacture or intended use" per US Federal Regulation 21 CFR 807.81 (a)(3).1
Global medical device sales are estimated to increase by 6.4 percent annually from 2016 to 2020, reaching nearly €367 billion ($440 billion).2 While the Americas are projected to remain the world's largest medical device market, the Asia-Pacific and Western Europe markets are expected to expand at a quicker pace over the next several years.3
In 2011, the medical device market in the EU accounted for one-third of the global market, with around €102 billion ($122.5 billion) in yearly revenue.4 The US is expected to continue to play a leading role in medical device R&D. After declining in 2009, R&D spending rebounded to $2.9 billion in 2010 and $7.3 billion in 2011. From 2013 to 2020, larger medical device companies are expected to increase their R&D budgets by approximately three percent, while the rest of the industry is expected to increase spending for this element by more than five percent.5
In the US, in order for a manufacturer to register and list a device as part of 21CFR Part 807, it requires the submission and clearance of a Premarket Notification 510(k) or the device cannot be commercially distributed legally. In an industry experiencing such growth, it is important for manufacturers to understand these 510(k) regulatory changes and implement revised Standard Operating Procedures (SOPs) to avoid misalignment with FDA further down the line as the device design evolves.
In August 2016, FDA posted a revision of the guidance "Deciding When to Submit a 510(k) for a Change to an Existing Device" which superseded the version which was introduced in 1997.6 In the new draft guidance, FDA sought to address the lack of clarity and provide clear definition of key terms in highly subjective criteria that has given rise to differences in interpretation and application of the guidance by industry professionals, such as "could significantly affect the safety or effectiveness" and "major change or modification."
Medical device and healthcare organizations are at significant risk of repercussions if FDA and industry reach a conflicting 510(k) filing decision. When industry determines a new 510(k) filing is not necessary for a proposed design or labelling change, it documents the non-filling decision, but it is still subject to future review and scrutiny by FDA at future site inspections. An FDA investigator may disagree with a company's non-filing decision that has been made previously, which could result in the investigator citing the firm for failing to meet 21 CFR 807.81 and issuing an inspectional observation (Form 483). The organization can then be issued with a warning letter or product recall if they fail to adequately address the noted deficiency. Other areas of misalignment between FDA and industry regarding the 1997 guidance include:
With the issuance of final guidance documents in October 2017, FDA realized its commitments to Congress by "preserving the basic format and content of the original, 1997" guidance and remained consistent with the 2016 draft guidance. In the final guidance, FDA expanded on the guiding principles and labeling requirements and added more clarity and examples. The 10 new "guiding principles" have a significant impact on the process, decision and documentation required are summarized below in Table 1.
Broader scope by definition and includes positive and negative changes
Labeling, Section A and the associated flowchart represents the most significant change between the final issue and 2016 draft guidance and increase the scope. The first question in A1 changed from a "substantive change to indications for use" to "a change to indications for use." FDA expanded and clarified that all indications for use changes are in scope, not just those deemed by the manufacturer as substantive.
The other significant change and increased scope is labeling section A4: "does the change affect the instructions for use" to "could the change affect instructions for use." FDA again opens the scope to include any possible affect of the change not those know to affect change.
Usability and over the counter clarification questions were also added. FDA increased the number of labeling examples in Appendix A from eight to 11 addressing industry comments and requests.
Sections B, C, D, and E remain primarily unchanged from the draft.
The final software guidance primarily follows the 2016 draft with additional clarification and streamlined flowchart. FDA considers all software changes to be design changes by definition and added additional emphasis in the final guidance regarding what could significantly affect safety and effectiveness. Table 2 is an example flowchart for organizations to follow and specifies when a software change requires a new 510(k) submission. The following questions lead the assessor through the logic scheme to a defensible software change 510(k) filing decision. Note: question 3a and 3b both need to be answered.
(same as draft)
(Draft #3 and #4)
FDA has clarified the significant role of risk management in the regulatory filing decision process. The burden is on industry to adopt and implement an effective risk-based change assessment process for its filing decisions. Several recommendations for updating existing regulatory filing decisions and processes related to design and intended use changes are provided below.
First, include an application/documentation of a risk-based assessment linked to your risk management process to substantiate your decisions.
It also is recommended that a comparison of the proposed changes against the cleared device be available and include current and aggregate changes since device clearance. Furthermore, software change assessment documentation must address the questions in Table 2.
It is recommended you look at your label review processes and the resultant documentation requirements and ensure they are robust and cover the full "new" scope of the guidance.
Key functional stakeholders should be able to provide expert input to address clinical, design and risk management considerations to ensure a fully comprehensive and error-proof decision process. It is advisable to do trial runs before implementing any changes. This is particularly important for smaller organizations or those with infrequent design changes.
Further considerations include the addition of a functional "swim lane" into the decision-process flowchart so there is full clarity on role responsibility and deliverables, and flexible forms/templates (similar to FDA's Appendix B) would ensure full process scalability.
To comply with the final guidance, revised procedures, associated documentation and implementation into the quality management system will require cross-functional planning and execution as well as an increase in the time and resources required. FDA anticipates that because the new guidance documents only add clarification and the impact of these new procedures on organizations is negligible. Whether this is true and if there is an increase in A510(k) submissions as a result of the change remains to be seen.
Jeff Ryberg is an active enterprise member of the Regulatory Affairs Professionals Society (RAPS) and holds the position of vice president, regulatory affairs and quality assurance, Danaher Business System Integration and Special Projects for Danaher Corporation. Ryberg has 30 years of experience in medical device quality and regulatory affairs and supports Danaher's diagnostics, life sciences, dental and water technologies businesses. He holds an MS in regulatory science from Johns Hopkins.
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Cite as: Ryberg, J. "A Regulatory Perspective: FDA Final Guidance for Design Changes Requiring new 510(k) Submissions." Regulatory Focus. February 2018. Regulatory Affairs Professionals Society.