There are several reasons why medical devices are modified once they are on the market. Although many types of changes happen in medical devices, today, our focus will be primarily on medical device labeling.
Before we proceed, let’s understand one thing – not all labeling changes would need a new 510(k) submission. It is the responsibility of the medical device legal manufacturer to assess and understand whether the labeling changes he intends to make call for a new submission. This assessment is primarily based on understanding the impact of the change against the 510(k) clearance that’s already been obtained for the medical device.
Note: Most medical device labeling changes do have far-reaching consequences for the manufacturing and marketing of devices. This is why proper assessment is a must.
Now, let’s dive right into the changes that trigger a new 510k for an already cleared device.
What are the different labelling changes that require a new 510(k)
1. Any Change that significantly impacts the safety and effectiveness of the medical device
If a manufacturer makes any changes to a device that could significantly impact its safety and effectiveness, a new submission will be required.
Even if the changes aren’t intended to affect the device’s safety or effectiveness, they should still be evaluated for any potential impact. This evaluation may lead to a new 510(k) filing.
2. Change from single-use only to reusable
The risks associated with single-use and reusable medical devices can be significantly different. This is why when a manufacturer changes a device’s labeling from single-use to reusable, it is a must to get a new 510(k) submission processed.
In case of this change, there are several new and different questions around safety and efficacy that need to be addressed, such as how effective are the disinfection or reprocessing steps that are employed for reusing the product, have these steps been fully validated utilising a contamination soil that may be equivalent to the one found in a clinical setting where the device is used, etc.
Note: Contrarily, switching a device from reusable to single-use typically does not require a new submission.
3. Changing labelling from Prescription (Rx) to Over-the-counter (OTC) use
Any changes to a device’s usage instructions can greatly affect how safely and effectively users operate it. In most cases where the manufacturer makes a change from prescription-only (Rx) to Over-the-counter (OTC) the impact on its safety and effectiveness varies significantly, calling for a new 510(k) submission.
As it must be evident, when there is a change from Rx to OTC, the target users operating the device are very different. Rx indication mostly comprises trained, experienced, or qualified healthcare professionals using the product, whereas OTC comprises layman users of different educational levels. Such a shift in indication raises several important questions around labeling comprehension and usability which are in turn related to the safe and effective use of the product. Thus, calling for a new 510(k) submission.
4. Changes that describe a new condition, disease, and patient demographic
If a medical device is updated to address a new disease, condition, or patient group, a fresh 510(k) submission may be necessary.
The FDA might see these changes as potentially impacting the device’s safety and effectiveness.
For example, let’s say a device was previously approved for use in patients with stage 4 cancer, and now the manufacturer wants to expand its use to include stage 3 cancer patients. In this case, a new submission would be required. Such changes could introduce new risks or alter existing ones. Hence, doing a thorough risk assessment is essential.
5. Changes made in user or use environment
Changes in who uses a device or where it’s used can impact its safety and effectiveness. This kind of change typically requires a new 510(k) submission because different environments bring unique challenges and may require different levels of supervision.
Similarly, if a manufacturer adjusts the device’s instructions for healthcare providers with varying training levels, a new submission may be needed.
Different training levels can also affect the device’s safety and effectiveness.
For instance, shifting a device from professional use in a hospital to home use will likely change its risk profile, as also discussed above under the Rx to OTC change.
6. Changes in frequency or duration of use
Changes in how often or how long a device is used can impact its performance and safety.
This includes using the device more or less frequently, changing how long it’s used for a task or treatment, or switching between periodic and continuous monitoring.
Manufacturers should assess how these changes might affect the device’s performance and whether they increase its risks.
7. Change from general use to specific use
These changes involve specifying a particular use for a device that was originally approved for general use.
Let’s understand it through an example.
A medical device company makes catheters that are cleared for general use in various medical procedures, including but not limited to draining fluids, administering medications, and collecting urine. In this case, the device is marketed as a general device which is suitable for various clinical applications and is not specified for a particular condition or patient population.
The medical device company then decides to modify the catheter’s design and materials and specifically indicate the device for bladder drainage in patients with urinary retention.
In this example, the catheter will be tailored and modified to meet the new labelling. The catheter’s performance will be enhanced in the urological context where the catheter will have a more flexible tip, coating to minimize the risk of infection, and biocompatible materials that reduce irritation.
All these are significant changes which need to be assessed from a safety and efficacy perspective by the FDA and hence this requires a new 510(k).
8. Change in Contraindication of the medical device
a) Changes to a device’s contraindications (situations where the device shouldn’t be used) can significantly impact its safety or effectiveness and usually require FDA review.
However, if new information (through post market surveillance or other studies) suggests adding a contraindication to protect public health, the FDA generally allows manufacturers to update their labels and notify users immediately.
These are the situations or changes that call for a new labeling and hence, should be submitted to the FDA as a “change being effected” (CBE) in a new 510(k).
b) Removing or modifying a contraindication typically requires a new 510(k) submission before making the change. This is because removing a contraindication can broaden the device’s use, potentially affecting safety.
For example, a blood pressure monitor included a contraindication excluding patients with lymphedema (swelling in the arms because of lymphatic system blockages) from the intended population for use of the device. Later, in the light of new evidence, the manufacturer wanted to modify the contraindication rather than remove it, suggesting that the device could be used safely by patients with mild to moderate lymphedema. This calls for a new 510(k) submission.
On the other hand, minor changes that clarify or reword a contraindication without altering its meaning usually don’t require a new 510(k) submission.
9. Changes in Warning or Precautions
Every manufacturer must regularly monitor how their medical devices are being used and collect user feedback. On the basis of user feedback, they should quickly update the warnings and precautions on the labeling.
Changes prompted by events reported under the medical device reporting (MDR) regulation, 21 CFR Part 803, typically don’t require a new 510(k) submission.
To Conclude
Medical devices often undergo various changes in design, functionality, clinical application, and materials due to process improvements, supply chain adjustments, or technological advancements. Many of these changes result in changes to device labelling.
Each change must be reviewed and approved and might undergo the change control process, which is typically a part of the medical device’s quality management system. Changes also need to be assessed for their impact via an impact assessment exercise. In the United States, any major modifications in the labelling that could impact a cleared device’s safety or effectiveness typically require a new 510(k) submission.
Labelling changes that don’t meet the regulatory threshold for a new 510(k) submission must be thoroughly documented. The scope and type of documentation can vary, but if testing or engineering analysis is part of the process, the results should be referenced or included. This involves providing a clear rationale for not submitting a new 510(k).
Finally, it’s important to stay mindful of changes throughout the lifecycle of your medical device, perform thorough analyses and maintain continued compliance.
