Any company that has recently applied for a Premarket Application or 510(k) clearance for their medical device may have noticed some significant changes in the application process.
The Food and Drug Administration (FDA), and more specifically the Centers for Devices and Radiological Health (CDRH), under pressure from several members of the US Congress as well as the Administration of President Barack Obama, have been more strident and slow in its willingness to approve or clear new medical devices for use in the US.
Device companies are being asked more questions by the regulatory agency, many of which appear to be outside the scope of the applied indication for the device under review. The result is that more US-based companies are looking elsewhere to commercialise their medical technologies.
Throughout this environment, some regulatory professionals have indicated that the FDA lacks the authority to recall medical devices that pose a significant threat to patients. Moreover, some express concern that the agency does not have enough authority in how it labels its products.
After examining the FDA's current labelling and recall authority, there is speculation as to whether some of these concerns are being driven by the current criticism of the approval process itself.
Criticism of the gold standard
Start-up and established companies alike have experienced noticeable slowdowns in their device applications to the FDA. While PMA-class devices have always required significant clinical data and scrutiny by the agency, the 510(k) clearance process has been a target for critics with claims that not enough data is being provided to the agency. Critics have also suggested that the 510(k) clearance route has become a 'fast-track' mechanism for novel medical devices, bypassing the more rigorous PMA process.
Over the last few years, criticism of the way the FDA handles device approvals has grown louder. From so-called patient advocacy groups to Members of Congress, the agency that handles device approvals seems to be under constant pressure from outside sources. Many point to a group of rogue reviewers from the CDRH as the genesis for the current climate affecting device approvals and clearances.
In autumn 2008, a group of eight unidentified reviewers from the agency sent letters to Members of Congress and the Administration critical of the review process and the way managers within the agency address scientific agreements. While the eight reviewers only represent a fraction of the total CDRH workforce, their message was loud and clear. Their letters referenced serious deficiencies in the regulatory process for medical devices and that the process itself had become 'seriously distorted'.
Building on this assertion, the group charged that certain agency officials had acted illegally by putting patients at risk by clearing devices despite objections from scientific reviewers. The group further claims that reviewers who disagreed with an approval or clearance of a device were retaliated against by senior agency officials because of their dissention.
The reviewer outcry, complemented by other elements and pressures against the agency, has led the agency to take several actions to address the concerns. In 2009, the agency issued an internal memo highlighting the actions of the CDRH in light of controversial clearance of an orthopaedic product. The memo pointed to potential lapses by the agency and became the catalysts for a top-to-bottom review of the CDRH. Specifically, following the release of the memo, the agency contracted with the Institutes of Medicine (IOM) to provide a comprehensive review, with recommendations, of the 510(k) clearance process.
In preparation for the IOM report, the Institute will hold public meetings to obtain public comments and is expected to issue its final report to Congress in 2011. Parallel to the IOM report, the FDA is also conducting a comprehensive internal overview and of the 510(k) clearance process and is expected to issue a report prior to the IOM report.
It is within this current environment and context that has given rise to questions about the FDA's recall and labelling authority for medical devices. Questions regarding the agency's ability to address concerns in the 510(k) system have led others to question whether its current authority related to overseeing potentially unsafe or ineffective products is sufficient.
FDA Compliance and Enforcement Authority
The concern over the 510(k) clearance process by the small, but loud, minority has given rise to questions about whether the agency possesses the appropriate level of authority to recall products that are deemed to be harmful or unsafe to patients. Most recalls in the medical device industry are voluntary.
Manufacturers are typically in the best position to detect whether or not adverse events are trending with their products. They have the ability to quickly work with their distributors to make sure products are taken out of the stream of commerce.However, the FDA has significant authority for product compliance and enforcement, including recalls, under current laws and regulations.
When a problem with a particular medical device arises, the FDA has several options. As a first measure, the agency is likely to work with the device manufacturer to address the issue and ultimately determine the severity and extent of the identified problems.
During this initial outreach, the FDA will determine if the appropriate manufacturing processes were followed and identify possible solutions to the problems. This approach is the most common when dealing problematic medical devices. However, absent success of this approach, the FDA maintains significant legal authority to take further action.
For example, the agency can take measures such as asking the manufacturer to recall the product itself, detain imports at the port of entry or even have federal marshals seize products.
If problems escalate, the FDA may seek further legal intervention and ask federal courts to issue injunctions. Companies should also be aware that the FDA can seek the federal courts to prosecute individual corporate officials and officers that have deliberately violated the relevant laws. This includes issuing criminal penalties including prison sentences.
All centres within the FDA have separate offices for compliance. Their purpose is to ensure compliance with all related regulations and guidance, labelling requirements and pre or post-market studies. Specifically for devices, the CDRH maintains the Bioresearch Monitoring (BIMO), which is designed to ensure the integrity and quality of data that is used to support device applications including 510(k) submissions, premarket approval (PMA) applications and investigational device exemption applications.
It is also tasked with ensuring that human subjects taking part in clinical investigations are protected from undue risk.
As part of the FDA's enforcement and compliance authority, the agency also maintains a significant degree of manufacturing and design practices of medical devices. For example, BIMO has the authority to review the quality system design and manufacturing information in most PMA submissions.
To this end, the agency is in a position to determine whether or not the manufacturer has described the manufacturing practices in enough detail. If the manufacturer information on any changes made to the manufacturing process is executed, the FDA will begin a preapproval inspection to assess the manufacturer's ability to design and manufacture the device as claimed in the application.
In communicating the risk, or even defects associated with a product, the FDA maintains the authority to ban devices that present substantial deception or unreasonable risk of injury to the patients. In some cases, the FDA can even require manufacturers to notify all health professionals who prescribe or use the device of any health risks associated with use of the device.
This also extends to importers, distributors, retailers and even device users. Within this section of the law addressing FDA's authority, patients and consumers have an established procedure for economic redress when they have been sold defective medical devices that present unreasonable risks.
Medical device recalls in most cases are conducted voluntarily by the manufacturer of the device. This process is conducted with consent and guidance from the FDA.
Recalls usually depend on the severity of the risk posed by the device and the time span in which it takes place. Some recalls may be either localised or can involve a total market withdrawal.
For example, some recalls may only be focused on a specific lot of products in which defects were found. While rare in occurrence, if a manufacturer or importer fails to voluntarily recall a device that poses a health risk, the FDA maintains the authority to issue a recall order directly to the manufacturer. In most cases, it never comes to this.
The FDA performs an extensive evaluation of the health hazard presented once a medical device recall is initiated. In doing so, it examines a list of factors including: whether any disease or injuries have already occurred from the use of the product; whether any existing conditions could contribute to a clinical situation that could expose humans or animals to a health hazard, assessment of hazard to various segments of the population (such as children, surgical patients, pets and livestock) who would be exposed to the product), an assessment of the degree of seriousness of the health hazard to which the populations at risk would be exposed, an assessment of the likelihood of occurrence of the hazard; and an assessment of the likelihood of occurrence of the hazard.
Based on the evaluation factors described, the FDA concludes the assessment of the recall by assigning a classification to the recall at discussion. This is based on the degree of health hazard posed by the device.
Class I recalls are the most serious types of recalls and are used in cases where there is a significant probability that using the device, or exposure to it, will cause serious adverse events or even death.
Class II recalls are used for scenarios where the use of, or exposure to, a medical device may cause temporary or medically reversible adverse health problems, or if the chances of such events are remote. The least severe level of device recalls is Class III, which is reserved for recalls that are not likely to pose any level of significant patient harm.
More authority for the FDA?
So what does all this mean for the medical device industry? Does the FDA need more labelling or recall authority than it currently possesses? From the perspective of the industry, and many regulatory experts, the answer is no.
The genesis of this debate has its roots grounded in the debate regarding the 510(k) clearance process. In short, a small but loud minority is attempting to lay the groundwork for a potentially massive overhaul of the clearance process, and possibly further implications for the PMA approval process.
Questions raised in this discussion have led many to opine on how much authority the FDA needs to perform its mission in ensuring the health and safety of the us public. In doing so, questions such as whether the agency has sufficient recall and labelling authority are being discussed – and the US Congress is paying close attention to this debate.
Historically, when Congress has modified or enhanced the laws governing the approval of medical devices or the FDA's authority in overseeing them, it has done so on an infrequent basis.
On average, the industry expects that any significant revisions to law will come once every five years, which coincides with Congress's obligation to reauthorise the laws governing medical devices and the agency's ability to collect user fees for product review by the agency.
Most recently, Congress reauthorised the device laws in 2007, and will likely do so again either in late 2011 or 2012.
The discussion on the 510(k) clearance process and potentially modifications to the PMA approval process will play out over the next two years. Congress is unlikely to take any action on these two issues until the IOM has released the finding of its review in the summer of 2011 and after the FDA issues its own assessment of the agency.
If recommendations are made for legislative change, the reauthorisation of the medical device laws in 2012 will likely be the vehicle for these to be accomplished. More importantly, that will also be the likely vehicle for changes to the FDA's recall and labelling authority should members of Congress feel that there is an adequate reason to do so.
Preparation for change
Momentum for change in the recall authority for the FDA will likely be muted. After a thorough examination of the agency's current authority to recall products, it is difficult to make the argument that the regulatory body cannot take the appropriate action when a product is found to be defective or impose a threat to patient safety.
In most cases, the FDA, working collaboratively with the industry, has been successful in identifying risks to patients. Moreover, the industry maintains a high rate of developing and delivering safe and effective medical devices.
As more evidence is produced that the current system works, the bar is set higher to justify making a change to the recall authority. Nevertheless, device manufacturers should be aware of the current regulatory environment and be prepared for change, whether it is warranted or not.