By Kirell Lakhman

The FDA's two-day public meeting on LDTs wrapped up yesterday in Hyattsville, Md., and I have to say I left pessimistically cautious.

As a clinical lab insider told me Monday morning, before the day's sessions even began, whatever the FDA's final decision will be, the "vast majority" of its components have already been set in soft stone.

Still, I take Elizabeth Mansfield, director for personalized medicine at OIVD, at her word when she said at the outset of the meeting that "all options are on the table." Of course they are (except, of course, the one that would keep things as they are).

So, below, some news and analysis.

After hearing from presenters and panelists and speaking with many sources, formally and informally, I've come to the conclusion that OIVD will likely play three small but powerful cards.

The crux will be in how powerfully it uses them and how clearly it illustrates the scheme. (We can only hope that at least in this regard it does a better job than its sister agencies in the military communities.)

First, based on the volume of comments about the subject, it will have to downgrade the risk classification for certain tests that it chooses to regulate, and not for altruistic reasons: Because it simply doesn't have the resources to regulate them all (FDA has said this on many occasions).

This will of course help clinical labs, whose potential net cost increase would decline. But OIVD would also end up regulating LDTs that aren't currently regulated, thus increasing the potential net cost to labs, especially those who aren't familiar with the 510(k) or PMA gauntlets.

Also, as I've written before, it seems that testing registries are the new black in Washington, and that most government agencies with a stake in public health funding have floated their own version. So it came as no surprise — as a relief, actually — to hear Mansfield suggest creating a joint-FDA/NIH database. As my colleague Turna Ray wrote yesterday, such a registry "could serve FDA's purposes for keeping an eye on all test developers."

Also, because CDRH and, by extension, OIVD, are chronically understaffed, underfunded, and overworked (not unlike the labs it is maneuvering to regulate), the agency will have to either hire more staff or employ contractors. FDA calls them "inspectors."

This, too, doesn't surprise me, not least because of the resource gap. As I've noted before, FDA officials are as slow as slugs when it comes to understanding existing and emerging technologies, and they need all the help they can get — which was presumably one reason for hosting the public meeting.

Here it's a question of choosing the lesser of two evils: The first option may be too costly, whereas the second may not work: Conflicts of interest, at the very least, can be very well hidden. And, as a source told me last week, outsourcing "has not worked well" in the past for FDA because the agency typically culls its stringer advisors from among "Ivory Tower academicians" who don't always approach new technologies from the perspective of the "real world."

But some disagree, saying such outside help may at least help FDA develop its new regulations: According to AMP, "[a]n external advisory committee would be a very valuable tool for the FDA as it works to make these determinations.”

Kudos to AMP

The two-day meeting did generate more light than heat at times, and I feel compelled to single out AMP for its courage in not mincing words. To me, the group, whom I have criticized in the past, has gotten it right on this one.

According to AMP, "all laboratories should meet CLIA standards, adhere to established guidelines, and seek appropriate certifications and accreditations."

AMP said it "believes that a regulatory model should not interfere with the practice of medicine, and it is important to recognize the value of the current oversight system for enabling clinical laboratories to rapidly incorporate new findings into practice and to modify existing laboratory tests and their usage in accordance with advances in our understanding of clinical utility and disease pathogenesis," Elaine Lyon, chair of the group's Professional Relations Committee, said during her 5-minute remarks.

“Nimble innovation in new test development is crucial to our ability to respond to emerging public health challenges, which was evident during the 2009 H1N1 influenza outbreak,” she said.

Indeed, on Monday, Steve Gutman, former chief of OIVD and current associate director of the Technical Evaluation Center with Blue Cross Blue Shield, said FDA can usher into the marketplace "yesterday" tests for public health emergencies.

Full points, also, for AMP for saying "LDTs in all disciplines of laboratory medicine should be subject to the same oversight mechanisms, and that molecular or genetic tests should not be singled out for heightened scrutiny simply due to the heritable nature of nucleic acids."

However, it conceded that "some tests may require greater scrutiny and may warrant additional regulatory review."

Alan Mertz, President of ACLA, told me as much last week when we spoke. Using carefully chosen words, he said for "some of these tests, because of the advent of personalized medicine and the incredible value of some of these tests ... there is maybe a role for a very small subset of them for the FDA to take a closer look at."

These tests include those that are performed and analyzed by a lab that "is the sole determinant of whether a patient receives a particular treatment," he said.

Likewise, "it’s important to recognize the potential impact of increased oversight on infrequent or low volume tests. Overzealous regulation of such tests could prove to be overly burdensome and cost prohibitive for laboratories developing and offering important but infrequently utilized tests,” said Lyon.

But as of now, according to a prominent Washington attorney who specializes in FDA regulatory issues, "It is still difficult to make financial forecasts. We'll have to see what FDA ultimately comes up with before they can be better refined.

"However, a broad regulation of LDTs by FDA will definitely be expensive," he cautioned.

Another problem Lyon mentioned is that "the recognition and implementation of advances in medical research may be hindered by a lack of certified reference materials" and said it would be a good idea to think about developing such materials, particularly at the National Institute of Standards and Technology. (The group made a similar point last month.)

AMP also highlighted the potential harm overzealous regulation can pose to clinical labs, something I have pointed out several times, most recently here.

According to AMP, overly burdensome regulations could have "unanticipated effects" that may "compel labs to discontinue services and/or potentially lose flexibility to rapidly introduce and continually improve tests, all of which would adversely impact delivery of effective care to our patients."

As ACLA's Mertz said yesterday in a statement, FDA "must recognize that clinical laboratories are not traditional medical device manufacturing facilities, and if strict medical device regulations are applied to the labs, important work in the development of cutting edge tests could be impeded."

ACLA On It

Like most clinical lab interest groups, ACLA, which presented Tuesday morning, "has been thinking about what the appropriate role" of FDA should be as far back as 2006, when the agency first floated its IVDMIA draft guidance.

When I spoke with Mertz last week he was preparing for the public meeting. He reiterated that "it's important as the FDA moves forward that it recognizes that laboratories are not traditional manufacturers; they're laboratories that provide a service for patients, for doctors, for hospitals."

But Mertz, who was a commentator during Tuesday's first panel discussion, told me that if FDA chose to go that route "there has to be an ongoing dialogue with the FDA, the test makers, and [other] stakeholders."

In yesterday's statement, ACLA revealed a handful of other specific suggestions:

First, FDA must "identify and better understand the differences between laboratory services and [IVDs] used by clinical labs to perform tests." It must also "reach consensus on gaps in oversight" and work "toward [a] consensus of the criteria for risk-based categorization of tests."

The agency must also "determine the appropriate evidence requirements linked to each risk-based category of tests" and "discuss the gaps between the FDA quality system regulations and the [CLIA] quality requirements."

For instance FDA must keep in mind that CLIA requires only analytical validation of a test, whereas FDA, along with CAP, demand analytical and clinical validation.

Finally, ACLA said FDA ought to "recognize … the need to grandfather the vast majority of well-accepted and well-understood tests already in clinical use to avoid disruption in patient care."

He mentioned this to me last week, and when I suggested that, surely, routine, non-esoteric tests would automatically be grandfathered in (assuming the new regulatory structure provided for such a mechanism), Mertz said, "We just don't know. The notice [FDA] put out for the public meeting was that they were considering regulating all LDTs."

"In their defense, I think this is why they're having this public meeting, and these are the issues they are struggling with," he added.

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