CEO SUMMARY: Officials at the FDA believe that CLIA does not go far enough because it does not address the issues of whether laboratory-developed tests (LDTs) have been designed correctly or have been manufactured in accordance with sound standards. Also, CLIA does not include a process to verify if LDTs are safe, accurate, or efficacious, said a legal advisor to labs. This may be why FDA views enforcement of new regulations as filling in gaps in CLIA or at least supplementing it.
SOME EXPERTS SAY THE FDA’S PLAN to regulate laboratory-developed tests (LDTs) has the potential to be one of the biggest changes to the practice of clinical laboratory medicine since the passage of CLIA in 1988.
On October 3, the FDA published proposed draft guidance in The Federal Register for the new LDT framework and notification requirements. This draft guidance started the 120-day comment period, after which the FDA will issue final guidance. Pathologists and laboratory directors wishing to submit comments that might affect the final regulations the FDA will issue, will need to submit those comments by February 2, 2015.
Given the lab industry’s high interest in the FDA’s proposed regulation of LDTs, THE DARK REPORT sponsored a recent webinar where attorneys Rick Cooper and Jane Pine Wood of McDonald Hopkins explained the steps that clinical laboratories need to take to prepare for the day when these new rules become effective.
“The FDA proposed these rules because it believes that, although CLIA regulates labs, CLIA does not go far enough,” commented Cooper. “The FDA is of the opinion that CLIA is not adequate to regulate LDTs because CLIA does not address such issues as whether LDTs have been designed correctly or have been manufactured in accordance with sound standards. Additionally, the FDA believes there is a need for a test-specific process that a lab must use to verify that its LDTs are safe, accurate, or efficacious.
Assessing Safety Of LDTs
“FDA officials are also concerned that CLIA does not account for post-marketing safety monitoring and data gathering in support of that type of assessment,” continued Cooper. “Seen from this perspective, the FDA views its enforcement of LDTs as filling in gaps or supplementing CLIA in a useful way.
“Another source of concern at the FDA is the probability that some labs are marketing unnecessary tests to clinicians and even selling these tests directly to consumers,” he stated. “Another potential issue is that some LDTs currently marketed to clinicians may be less efficacious and cost more than other tests already available in the marketplace.”
After explaining why the FDA believes regulation of LDTs is necessary, Cooper offered three considerations for labs. First, the fact that the FDA delivered a detailed description of how it will regulate LDTs is significant, he said.
“The LDT draft guidance is detailed and, for that reason, it gives us insight into how the FDA wants to see enforcement roll out,” he noted. “Quite often, these proposals are not this detailed. It shows that the FDA has given considerable thought into how it will pursue enforcement.
“Second, the FDA’s proposed guidance calls for putting the various elements for the proposal in place over time,” he stated. “Because the various enforcement components will not be implemented immediately, labs will have time to comply.
“Many labs, particularly those performing LDTs that will be subject to the most stringent compliance requirements, will need to make meaningful changes in the way they operate,” noted Cooper. “That is why the FDA’s proposed extended timeline will be critical as labs take the needed steps to comply with these new regulations.
“Third, some lab directors and pathologists believe that specific LDTs they currently perform in their labs will not be subject to the new rules,” emphasized Cooper. “This belief is incorrect.
“There will be no grandfathered LDTs,” he said. “Therefore, labs rushing to introduce new LDTs into the market before these rules take effect will gain no significant advantage, at least given the draft language issued by the FDA.
” With the release of the draft guidance on the LDT framework and notification process, the FDA is expected to take progressive steps to develop implementing regulations. “After the public comment period, the FDA’s next step will be to announce the language of the guidance, which will disclose the date when the guidance takes effect,” stated Wood. “The FDA is proposing a nine-year process to phase-in these regulations. But that doesn’t means labs can do nothing. To the contrary, within six months of the issue date of the final regulations, most labs performing LDTs will need to take steps to comply.
“The first step to comply with the LDT rule (as contemplated in the proposed guidelines, which are subject to change from the draft as currently written) involves the notification requirement,” stated Wood. “Every lab will need to notify the FDA of the LDTs they are performing.
“Labs also will need to do some medical device and adverse event reporting associated with their LDTs,” she commented. “Adverse event reporting is needed to address a concern at the FDA regarding patient safety. The FDA believes it is not getting enough information regarding adverse events.”
Gather Data in Advance
“But the bigger issue involves notification. Within six months of the publication of the final guidance, labs will need to notify the FDA about each LDT,” emphasized Wood. “To get a head start on this process, labs should start thinking about which of their tests meet the definition of an LDT.
“Should a laboratory fail to comply with this notification requirement, the penalty would be to go through the FDA’s pre-market review process,” she said. “Complying with notification is important because most labs would be hoping to avoid the time and expense of a pre-market review.
“What concerns some lab directors who have studied the notification requirements is whether their existing LDTs will fall into the category of tests that will require pre-market review,” noted Wood. “The FDA will make decisions about the need for pre-market review based on the risk classification scheme described in the proposed LDT rule.”
Wood and Cooper pointed out that the FDA is proposing to use its existing classification scheme. Thus, lab tests deemed to be Class I devices will have the lowest risk. Class II tests will have moderate risk and Class III tests will have the highest risk. “We know the FDA will require pre-market approval for Class III devices, per the language of the proposed rule,” observed Wood. “Class III will be the highest hurdle for any laboratory seeking to get LDTs to market.”
“This is what makes the notification process important—both to labs and the FDA,” noted Cooper. “The FDA will gather information on LDTs through the initial notifications. It will then classify each LDT and notify laboratories about that classification.”
“It is expected that the notification process itself likely will be electronic,” said Wood. “The FDA will look for information on every LDT, including monthly test volume, intended use, testing method, sample type, analytes that are used or the organisms that are detected, the clinical use of the test, and the patient population.
FDA To Use Expert Panel
“Based on this information, the FDA will determine a risk classification,” stated Wood. “The FDA will involve consideration of such factors as the risk level of the disease involved, the type of clinical decision involved, if the test is screening or diagnostic, if the LDT is the sole information upon which a clinician would make a decision to treat the patient, and whether there are any other testing options available. Expert panels will advise the FDA concerning how it should classify LDTs.”
Given that the FDA’s proposed new guidance represents such a significant change in how LDTs are regulated, it is important for pathologists and lab managers to stay informed about the new guidance and dates for its implementation.
FDA’s 9-Year LDT Review Could Start Next Year
CLINICAL LABORATORY DIRECTORS AND PATHOLOGISTS have until February 2, 2015, to comment on the two documents issued by the FDA issued on October 3. The documents provide draft guidance on how to implement a new regulatory oversight framework for laboratory-developed tests (LDTs).
In a presentation for THE DARK REPORT, Jane Pine Wood of McDonald Hopkins explained that the FDA could take as much as nine years to implement this regulatory oversight. The first step in the implementation has already begun, That is the 120-day comment period which began October 3 and ends on February 2, 2015.
The next step will begin six months after the final guidance is published. This next step is the process when labs need to notify the FDA about the LDTs they provide. It is possible that the FDA will issue final regulations by the summer of 2015 at the earliest, Wood estimated. At the same time, labs would need to notify the FDA about the LDTs they offer and any adverse events resulting from the use of these LDTs, Wood said.
“Following the six-month review, the FDA will begin enforcing the premarket review requirements, about 12 months after the final guidance is published,” Wood said. “The FDA’s review will begin with the highest-risk LDTs. This review will be phased in over four years because the FDA will commence reviewing the highest-risk LDTs before proceeding to review those LDTs it designates as lower risk.
“After the FDA completes its review of high-risk LDTs, it will next review moderate-risk LDTs. That will begin five years after the guidance is finalized, and the phase-in will be over an additional four years. That’s how we get to nine years altogether for a phase-in period,” she said.
