FDA Suspends LDT Regulation, But Liability Still in Play

After two years and seemingly endless sturm und drang, the FDA’s device center has announced it will suspend its proposed framework for regulation of lab-developed tests. The agency made it clear this is not the end of its interest in the matter, but Congress has an eye on this issue as well, which makes the outcome of all this activity difficult to forecast. If there is anything resembling certainty in all this, it may be that lab-developed tests will soon be subject to more liability under state tort law.

PMA Preemption Likely to Hold

The FDA said in its Nov. 18 announcement that the agency is aware of the importance of working with “stakeholders, our new administration, and Congress” to forge the appropriate approach to regulation of lab-developed tests (LDTs). However, the statement includes the remark that the FDA will publish an outline of what the agency sees as an appropriate risk-based paradigm for LDT regulation “in the near future,” which could be used to “help guide continued discussions” on the subject. Clearly, the FDA intends to stay in the game as this controversy evolves in 2017, although it is interesting to ask whether the agency would have pulled back on the draft had the presidential election yielded a different result.

The House Energy and Commerce Committee had floated a discussion draft of a new framework for regulation of LDTs in 2015, which calls for the establishment of a new center at FDA that would regulate these tests, and which would report to the FDA commissioner “in the same manner as the other agency centers.” This passage would seem to put LDTs on the same regulatory footing as therapeutic devices, which in turn would suggest a similar legal status where preemption of tort law for PMA devices is concerned. The draft also cited preemption with the statement that the states would not be allowed to sustain any existing or establish any new requirements for LDTs that would be “different from, or in addition to” the mandates set out in the discussion draft, a seemingly familiar passage that presumably would not pertain to tests cleared under the 510(k) program.

Regardless of how the preemption question evolves, there are a number of parties who have expressed concern about the potential for an LDT-specific regulatory regime to increase legal exposure. The American Society for Human Genetics said in a Feb. 2, 2015, letter to the FDA that the agency’s proposed LDT regulation framework would subject tests for genomic purposes “to the states’ strict product liability tort regimes.” The American Clinical Laboratory Association raised a similar set of concerns in a June 2013 citizen’s petition to the FDA requesting the agency scupper the LDT regulation effort.

Lawsuits Already a Risk

There have already been several liability cases for LDTs, including the wrongful birth case in the state of Washington that cost LabCorp – and the hospital where the test was conducted – a total of $50 million. LabCorp was on the receiving end of another lawsuit, Khadim v. LabCorp, a case the company managed by having itself identified in legal terms as a provider, which in Virginia limits the damages available to plaintiffs. It does not seem a stretch to imagine that provider status under state law would suffer in a formal federal regulatory environment.

There are other ways the FDA can boost its enforcement activities in this area, such as the issuance of a safety alert, a move that would lead to increased media scrutiny and possibly media coverage-driven lawsuits. There is one inescapable fact to consider, however: Modern medicine’s reliance on LDTs will continue to increase and grow increasingly visible, particularly as gene sequencing technologies become less expensive and more commonly used to determine a course of treatment that may or may not achieve the desired result.

Obviously there are several moving parts to this predicament, but the net effect is unavoidably that the stakes for makers of these tests will grow, regardless of how Congress, the FDA and the White House answer the LDT regulation question.

New Guidance from FDA: When to Submit a 510(k) for a Change to a Cleared Medical Device

Courtney A. Stevens, Esq. |Senior Attorney, Medmarc Loss Control

FDA’s newest guidance for medical device manufacturers, Deciding When to Submit a 510(k) for a Change to an Existing Device, issued August 8, addresses a question manufacturers commonly face,—when a 510(k) is necessary for a change to an already cleared device. Manufacturers’ failures to submit 510(k)s are frequently cited in warning letters as rendering a device adulterated. As such, it’s an issue medical device companies can’t be too careful in scrutinizing. Thankfully, this guidance does provide such much-needed clarity on exactly when a 510(k) is necessary, and when processing the change in accordance with Quality System (QS) requirements (e.g., documentation of changes and approvals in the master record, verification and revalidation, etc.) is sufficient.

The confusion over whether a 510(k) is necessary is largely due to the subjective, relative language in the regulations, requiring device-makers to submit a 510(k) when a change “could significantly affect the safety or effectiveness of the device.” (21 CFR 807.81 (a)(3)). The Agency tried to clarify its interpretation of that language in its first guidance document on this issue, published in 1997, but clearly, as evidenced by the frequency with which the manufacturers’ determination of “significant” changes differed from the Agency’s, greater clarity was needed still. (Once finalized, this draft guidance will supersede the 1997 Guidance on the subject.)

This guidance document improves upon its predecessor by providing a number of exacting flow chart-decision trees to guide manufacturers through the determination of a 510(k)s’ necessity with regard to different types of changes.

It begins by setting out the guidance principles to be first considered in determining the propriety of a 510(k), which I briefly summarize here:

  • Modifications made with intent to significantly affect safety or effectiveness of a device. This is the same language as is found in the regulations, and its meaning is fleshed out in the remainder of the document.
  • Could “significantly affect” evaluation and the role of testing. In order to determine significance of the effect, manufacturers must conduct risk-based assessments.
  • Unintended consequences of changes. One component deemed to make up a “significant effect” is if the change would result in unintended consequences or effects. The draft guidance provides sterilization as an example which may affect device materials, thereby affecting performance of the device.
  • Use of risk management. Here, the draft refers to ISO 147981: Medical devices – Application of risk management to medical devices, and instructs manufacturers to utilize an assessment combining the probability of occurrence of harm and the severity of that harm in determining “significant effect.”
  • Evaluating simultaneous changes. Even though changes may occur simultaneously, each change should be assessed individually and in combination.
  • Appropriate comparative device and cumulative effect of changes. In making the determination of a 510(k)’s propriety, manufacturers need to consider (1) how different a change makes the device from its initial or most recent iteration as described in their most recently cleared 510(k); and (2) the cumulative effect of all changes since the last 510(k) cleared for this device. That is, though previous changes did not require a 510(k) when made in isolation, does the cumulative effect of this change with those previously made nor warrant a 510(k), even if it, by itself, would not?
  • Documentation required. Even if a manufacturer determines a 510(k) is appropriate for a particular change, this does not alleviate them from compliance with all existing QS requirements, including all documentation, verification, and validation duties.
  • 510(k) submission for modified devices. When a 510(k) is submitted for a device with multiple modifications since its last cleared 510(k), the 510(k) should describe not only the most recent change that warranted the 510(k), but also all previous modifications even though they did not merit the submission of 510(k)s in and of themselves.
  • Substantial equivalence determination. Manufacturers need understand that submission of a 510(k) for a change pursuant to everything outlined in the regulation and this guidance document does not assure that a substantial equivalence determination will be provided.

 

With these considerations in mind, manufacturers may proceed to the different parts of the guidance instructing them on decision-making for different kinds of changes—labeling, control mechanisms, operating principles, etc. In each of these, manufactures will find the aforementioned decision trees to guide them through submission criteria.

An example of the flow charts included in this draft guidance:

8.16 - guidance flowchart

In addition to charts guiding decision making, the guidance also provides examples of documenting changes and written regulatory change assessments.

This should go a long way in facilitating manufacturers’ understanding of when 510(k)s for changes are necessary, and reduce the number of warning letters for companies’ failure to submit them, accordingly.

FDA Issues Draft Guidance: Postmarket Cybersecurity for Medical Devices

Jordan Lipp | Partner Davis Graham & Stubbs LLP

A little over a year after issuing final guidance on premarket submissions for management of cybersecurity in medical devices, discussed here, the FDA issued draft guidance on postmarket cybersecurity (available here).  The FDA’s stated purpose of this draft guidance, which it just issued, is to clarify “FDA’s postmarket recommendations and [to] emphasizes that manufacturers should monitor, identify and address cybersecurity vulnerabilities and exploits as part of their postmarket management of medical devices.”  As cybersecurity threats are continually evolving, the FDA explains that it is not possible to completely mitigate cybersecurity risks solely through premarket controls.  Recognizing that “medical device cybersecurity is a shared responsibility between stakeholders,” the draft guidance addresses both risk management and remediation of cybersecurity threats.  It also discusses the interplay of cybersecurity issues and medical device companies’ reporting requirements, setting forth several examples of what should or should not be reported. Continue reading “FDA Issues Draft Guidance: Postmarket Cybersecurity for Medical Devices”

Regulatory Roundup: FDA Reports and Guidances in August

Courtney A. Stevens, Esq. | Senior Attorney, Medmarc Loss Control

Recommendations for a National Medical Device Evaluation System

On August 20, the FDA released, for public comment, a report from the Medical Device Registry Task Force and the Medical Devices FDA logo.jpgEpidemiology Network. The report described the inadequacies in the existing framework for medical device evaluation, what a more effective system would look like, what devices would be particularly ripe for evaluation via such a system, and how the system could be implemented. The full report can be found here.

FDA Issued Several New Drug and Device Guidances

The Agency issued several new guidance documents in August, including the following. Continue reading “Regulatory Roundup: FDA Reports and Guidances in August”

FDA New Draft Guidance: Medical Device Clinical Data from Trials Outside the U.S

Courtney A. Stevens, Esq. | Senior Attorney, Medmarc Loss Control

Last week, the FDA released draft guidance for medical device developers on utilizing clinical data obtained from trials conducted outside the United States. Many view this Guidance as a follow-up on a proposed rule the Agency issued in 2013 (Human Subject Protection; Acceptance of Data from Clinical Studies for Medical Devices), which would require that foreign trials comply with U.S. good clinical practices regulations if in support of a device application. In furthering this effort toward uniformity and consistency among trials internationally, this most recent guidance clarifies the participant protections that need be in place in order for the data to be deemed reliable by the Agency for purposes of application review. Continue reading “FDA New Draft Guidance: Medical Device Clinical Data from Trials Outside the U.S”

FDA Reopens Comment Period on Generic Drug Labeling Proposed Rule

Jordan L. Lipp | Partner, Davis Graham & Stubbs LLP

Bowing to pressure from stakeholders and Congress, on Tuesday FDA announced that it would reopen the comment period (through April 27, 2015) for its proposed rule that would allow generic drug manufacturers to unilaterally change their labels.  And, FDA set a public meeting for March 27, 2015, in order to “provide a public forum for FDA to listen to comments on the proposed rule.”  As discussed in more depth in an earlier post, FDA’s highly controversial proposed rule would permit generic drug manufacturers to unilaterally change their labels under changes-being-effected (“CBE”) process, which not only would result in the potential for generic and brand-name labels to differ, but would also threaten to undermine recent generic drug preemption decisions by the U.S. Supreme Court. Continue reading “FDA Reopens Comment Period on Generic Drug Labeling Proposed Rule”

FDA Issues Draft Guidance on General Wellness Products

Courtney A. Stevens, Esq. | Senior Attorney, Medmarc Loss Control

On Friday, January 16, the Food and Drug Administration published two draft guidances pursuant to its FDASIA-mandated Health IT Report, released in April of last year: (1) General Wellness: Policy for Low Risk Devices; and (2) Medical Device Accessories: Defining Accessories and Classification Pathways for New Accessory Types. This post discusses the first.

General Wellness Products

The first draft guidance, General Wellness: Policy for Low Risk Devices, does very little in the way of policy. Rather, the majority of the Guidance is devoted to defining what general wellness products are and helping industry determine whether their devices fall under this policy. Continue reading “FDA Issues Draft Guidance on General Wellness Products”