What are the top ten FDA regulatory initiatives from the FDA that will affect the orthopedics industry, surgeons and hospitals this year and beyond?
Ralph Hall / Source: reilly.nd.eduRalph Hall, a professor of law at the University of Minnesota and counsel for Baker & Daniels answered that question before a packed house of medical device manufacturers at a Minnesota LifeScience Alley meeting on August 31.
Hall said there is currently “more action than ever” at the FDA. He cites pressure from consumer groups who point to DePuy’s ASR hip recall as an example of what the FDA’s interprets as lax oversight.
He notes the recently released Institute of Medicine (IOM) recommendation to scrap the 510(k) system has the potential to be used by consumer groups to call for tighter regulations. While the FDA said it has no plans to follow IOM recommendations, Hall pointed out that some physicians, speaking through the New England Journal of Medicine, have come out in support of the IOM recommendations.
Within this broad context of the condition of the U.S. device regulatory environment, Hall outlined key FDA CDRH (Center for Devices and Radiologic Health) initiatives that should keep device manufacturers and providers awake at night over the next few months. We identified what we thought were the top ten important items for the orthopedics community.
Notice to Industry SOP (Standard Operating Procedures)
The FDA wants to provide faster communication of new “requirements” and new scientific thinking. According to Hall, the agency wants to “level the playing field, ” and help orthopedic manufacturers adapt faster to the vicissitudes of the FDA’s thinking and to provide more agency action predictability.
Chemical Guidance
This little known guidance, according to Hall, has been under the radar and deals with complex, philosophical questions in differentiating drugs and devices. An expansive definition will push more products into the drug regulatory system, says Hall.
The draft seeks to define “chemical reactions” that mediate a bodily response at the cellular or molecular level, or combines with or modifies an entity in a way that affects that entity’s interaction with the body, as the “formation or breaking of covalent or ionic bonds.”
Hall says that while many devices are purely mechanical and are not affected, it is innovative therapies that will be at greatest risk. He cites electrical pulse, cautery and ablation, cold and radiation products as examples.
Mobile Medical Applications
This topic includes direct medical applications through the use of a mobile device or applications as an accessory to other products. Examples include remote displays of data from bedside monitors, patient screening tools, and wireless remote controls for devices. Excluded are electronic health records, general health and wellness applications, and books, articles and other teaching materials.
“This will pull the Silicon Valley developer into the FDA, ” said Hall.
The FDA is attempting to determine the appropriate regulatory classification for the devices and whether or not the device is “medical” or not. The guidance was issued on July 21. A public workshop will take place September 21-22 and final comments are due October 19.
Clinical Trial Guidance
The purpose of the guidance is to assist in the design of pivotal studies. The guidance excludes feasibility and postmarket studies.
Hall says that some general factors for consideration for the studies include: population diversity, variable device performance, availability of alternative therapies, intended uses and bias, and variability. The guidance is linked to the risk/benefit draft guidance and discusses least burdensome concepts.
Hall emphasizes that the guidance strongly encourages randomized studies, prefers concurrent controls compares risks with non-comparative or observations studies.
RUO/IUO Guidance (Research Use Only/Investigational Use Only)
For decades, says Hall, “intended use” has been based on the “objective intent” of the manufacturer. This proposed guidance changes that presumption to a “reason to know test for intended uses.” Such a change can have a major impact on off-label use and company risk, according to Hall.
For example, a company would not be able to sell the device to a research university if the company has “reason to know” that the product will be used off-label in research. Under this guidance, unsolicited third-party actions can be attributed to the manufacturer.
Other questions raised include what happens if a hospital uses a product off-label 5% of the time and tells the sales rep? What if a competitor tells your sales rep that the customer was using the product off-label? Could you still sell it?
Clinical Investigator Monitoring
Hall says sponsors should preplan monitoring programs that encourage central monitoring instead of relying completely on on-site monitoring. Sponsors should identify critical monitoring points, activities and data and review policies and procedures as well as actual implementation.
The FDA’s goal in issuing this part of the guidance is to try to improve human clinical study subject protection and data quality. In the draft guidance document, the FDA called for using risk-based monitoring but they didn’t ask for 100% verification.
Risk Benefit Guidance
The guidance, according to Hall, lets the nose of the comparative effectiveness camel under the tent. It recognizes different types of clinical data, but, according to Hall, seems to prefer randomized clinical studies and data over other types of clinical studies and data.
Various effectiveness and safety measures with intended use are considered. Such measures include: type, magnitude, probability and duration of benefits, and adverse events. Additional factors include: patient tolerance for risk and availability of alternative therapies. Hall questions whether the FDA should be making patient risk tolerance decisions. “Isn’t that the practice of medicine?” he asked.
522 Postmarket Surveillance Studies
On May 6, 2011, the FDA sent out letters ordering 21 makers of metal-on-metal hips to submit plans for conducting postmarket studies on patients who have received the device. The agency wanted to know whether or not the implants are shedding high levels of metallic debris into patients.
The agency is now looking at ways 522s are triggered and the process for assurance compliance.
Hall said pressure for tightening up the 522 surveillance system is partly due to high profile recalls. In his opinion, medical device manufacturers have failed to complete postmarket studies promised during the approval process. He noted that new interim reports may be required and committed to as part of the approval process. Studies can range from randomized clinical studies to active surveillance to bench tests.
510(k) Device Modifications Submissions
There is a new statutory obligation which requires manufacturers to submit a new 510(k) on a previously cleared device if a change to that device has been made that “could SIGNIFICANTLY affect safety and effectiveness.” The agency issued draft guidance for manufacturers to use in these cases.
In Hall’s view, the FDA guidance will have an effect on manufacturing process changes, suppliers, software changes and upgrades, labeling and packaging.
Here are five specifics that each orthopedic manufacturer should ask themselves about their existing, already cleared 510(k) devices:
Manufacturing – Was the manufacturing process information in the original 510(k)? If so, Hall says a submission is likely needed. Most packaging changes will not need a 510(k). However, use of methods or protocols not in the original 510(k) to confirm package integrity will probably trigger a submission.
If the manufacturer is changing from a non-sterile to sterile device, a submission will be required.
Labeling – Almost all changes to indications for use will need to be submitted. Removal of intended uses or indications for use for purely marketing reasons will not need a submission.
Contraindications – All new/modified contraindications must be submitted. Adding a contraindication prior to FDA clearance will render the product adulterated and misbranded. He cautioned manufacturers that tripping on this issue can subject them to False Claims risks, contract violations with customers and removal of the protection of “preemption” from product liability suits in state courts. A submission will also be required if a contraindication is removed.
Use Changes – Changes in possible off-label use may require a change. For example, a modification that COULD create a reasonable likelihood of off-label use would require a submission. The intended use promoted by the manufacturer is not relevant if there is that “reasonable likelihood” of off-label use. As an example he cited lengthening surgical scissors so that they could now be used in an endoscopic procedure. That would need a submission, even if labeling is not changed.
Submissions will be required if changes to the device allow new, expanded or more specific patient populations. Modifications that can alter an established medical procedure will also require a submission.
Materials – Changes to materials that “directly or indirectly” contact patient may need a 510(k). Hall says this category has the ASR hip problem written all over it. Changes in surface or surface preparation, such as changing from surface blasting to acid-etching will need a submission.
Use of Clinical Data – If clinical data is needed to assess the change because bench testing or simulations are not sufficient, then a submission will be required. Paradoxically, Hall says this will serve as a disincentive to use clinical data. For instance, a manufacturer who discovers that engineers seeking to be extra thorough with a device modification by checking on clinical data may inadvertently trigger a submission even if the clinical data was not needed.
And the number one FDA initiative that should keep you awake at night is:
510(k) Reform Activities
Over the coming 60 days the FDA will react to the IOM report and probably decide how to proceed with seven “contentious” issues identified by the FDA’s 510(k) reform plan earlier in the year.
Jeff Shuren, M.D., CDRH Director
Photo by Orthopedics This Week
In Hall’s opinion, the “radical” IOM report will give CDRH’s director, Jeff Shuren, M.D., room to look like the grown up on the reform effort.
When Hall looks at the FDA today, he sees a pattern of increasing regulatory activity in such areas as clinical data, 510(k) eligibility, off-label scrutiny and an increasing reliance on data, information, submissions and control. The FDA, he thinks, will continue to expand its attempts at being transparent and to centralize much of the CDRH decision making through the Science Council.
Strap yourselves in and pay attention. There’s more action than ever.
