Note: this is a recording of a LinkedIn audio event with Steven Silverman of the Silverman Group. The article below highlights a few key points from the discussion.
When it comes to engaging with the FDA1, there is a general sense of fear and anxiety in the medical device industry. After all, the FDA can shut you down and impose heavy fines if it finds you are not complying with the Quality System Regulation (QSR).
However, this is only one aspect of the Agency’s role in ensuring public safety through safe and effective medical devices. Since the question of safety and effectiveness is closely linked to benefit-risk, it is important for us to understand the Agency’s view on risk and how best to engage with it on the topic of risk.
Here are a few key highlights of the discussion with Steve on this topic.
1. How is the term risk viewed by the FDA?
Compliance with the QSR is currently the predominant view according to the established perspective at the FDA. The Agency is not looking at risk as an independent, stand-alone topic. Rather, the expectations is that risk management activities are integrated across the Quality Management System to ensure compliance with regulatory requirements.
Risk is folded in multiple places across the Quality System Regulation, and that is where the FDA is factoring in the risk.
As an example, risk considerations play a key role during Design Controls. FDA’s perspective is that good practices in design controls directly or indirectly demonstrate that risk has been accounted for and mitigated to the extent reasonably possible.
Once a device has been approved or cleared on the basis of valid scientific data demonstrating safety and effectiveness, there is an expectation of a baseline level of risk associated with a device. It is reasonable to expect that there would some malfunctions during actual use in the field, but the nature of risk is generally expected to be associated more with the use environment and not necessarily device failures.
We need to monitor complaints to make sure that device performance and our estimated level of overall risk continue to meet these baseline expectations. If there is an increase in the overall risk, then appropriate actions need to be taken in a timely manner.
2. How to best engage with the FDA when they have concerns about device safety?
FDA may raise specific safety concerns based on observed performance in the marketplace or as a result of inspections. Generally, FDA will provide a good rationale for its concerns, and in most cases, these concerns are legitimate. However, there may be situations where manufacturers may decide to elevate the discussion to a higher level to seek clarification or provide additional information before a significant enforcement decision is made.
Manufacturers have to make a decision about whether or not “the juice is worth the squeeze”.
In a situation where an FDA investigator makes an unreasonable or unrealistic assessment of risk during an inspection, it is appropriate to first engage in a dialog to clarify and align expectations in the context of safety and effectiveness. If there is still a deadlock, it is legitimate to acknowledge the disagreement and elevate the issue to the supervisory level in the FDA, while also keeping the investigator fully informed. It is important to maintain transparency in communication to ensure a trusting relationship.
In fact, the supervisory ranks in the FDA often appreciate when companies reach out to them with their legitimate concerns because it gives them a chance to review the investigator’s assessment and correct any mistaken observation that are not supported by proper evidence.
3. How to best engage with the FDA when you have an innovative device or a change?
If you think traditional QSR requirements are not applicable to an innovative device or a change you are working on, you should consult with the experts in the FDA through the Q-submission process2, rather than trying to review with an FDA investigator.
As an example, development of innovative digital devices is highly iterative in nature. They go through rapid changes during the development process as well as after launch. It may not be practical to interpret and apply the Quality System Regulation the same way you would apply them to a traditional hardware-only medical device.
It is important to figure out what the change is and if you need the FDA to shift its interpretation of the QSR to better fit the nature of the device or the change, and applicable manufacturing and/or quality practices.
FDA is very open to having a conversation with manufacturers, but you need to know the right people to go to.
If so, then this conversation is more appropriate for the regulatory decision-making process, and not during an FDA inspection, where the FDA investigator is simply executing a static set of requirements to a particular situation. They don’t have the authority to interpret the requirements and adjust them to your approach.
In Conclusion
FDA does not consider risk as a separate entity. The notion of risk is folded in multiple places within the Quality System Regulation (QSR).
When concerns related to risk in the context of the QSR are raised during an FDA inspection, it is important to clearly understand the rationale. In case of a disagreement that cannot be resolved during an inspection, it is perfectly legitimate to request a supervisory level discussion while maintaining full transparency with the FDA investigator.
Questions related to interpretation of the regulatory requirements for innovative devices or changes should be reviewed with professional experts at the FDA during the regulatory decision making process, and not with the FDA investigator during an inspection.
About Steve Silverman
Steve Silverman is president of The Silverman Group. Steve spent more than a decade at FDA in leadership positions across the Agency. He adds private-sector expertise from consulting and representing industry members. Steve develops strategies that satisfy regulators and promote business needs.
About Let’s Talk Risk with Dr. Naveen Agarwal
Let’s Talk Risk with Dr. Naveen Agarwal is a weekly live audio event on LinkedIn, where we talk about risk management related topics in a casual, informal way. Join us at 11:00 am EST every Friday on LinkedIn.
Disclaimer
Information and insights presented in this article are for educational purposes only.
The Q-Submission Program: Guidance for requesting feedback and meetings for medical device submissions
Understanding FDA's perspective on risk