According to Palombi, “Myriad’s objective in surrendering the ['004 Patent] is to bring the proceedings to a premature end.” Palombi contends that Myriad’s effort to surrender the ’004 Patent (pdf) is designed to avoid Australian litigation that could set a harmful (even if non-binding) precedent in similar and ongoing U.S. litigation. Myriad, for its part, has so far refused to comment publicly.

A Successful Strategy? As we wrote last week, even if this is what Myriad intends, we are not so sure they will succeed. Offering up the ‘004 Patent for surrender may be a first step in heading off litigation, but without more it is difficult to explain (1) why the plaintiffs would accept the patent surrender, particularly given their stated objective (pdf) to use this litigation as a “test case” for the validity of gene patents or, (2) even if the surrender is successful, why the plaintiffs would refrain from bringing a second “test case” challenging one or more of Myriad’s other patents covering BRCA-1 and BRCA-2 and methods for diagnosing mutations in those genes. (The plaintiffs’ current complaint identifies several of these patents, but challenges the validity of only the ’004 Patent.)

Other commentators have speculated that, given the apparently limited financial upside to Myriad from the Australian testing market, Myriad may not be interested in investing the time and expense (including negative publicity) necessary to litigate this issue in Australia. Even though Myriad’s President, Mark Capone, recently told investors that the company had secured representation for its legal activities at a fixed cost of $200,000 – a bargain made possible because, according to Capone, “the lawyers want their names on [the Myriad litigation]” – it is surely the case that Myriad would prefer to avoid this litigation and all of its attendant costs if possible.

Still, no matter how expensive or inconvenient the litigation, or unimportant the Australian market to Myriad’s bottom line, it is unlikely that Myriad would be willing to surrender the remainder of its Australian patent portfolio simply to avoid litigation. Doing so would not only open up additional competition within Australia, potentially impacting Genetic Technologies Limited, Myriad’s exclusive licensee in that country, it might also permit would-be Myriad competitors to provide Australian-based BRCA testing to customers in the United States, Europe and elsewhere. That could, in turn, threaten Myriad’s BRACAnalysis product, which accounts for nearly 90% of the company’s revenues.

Cause for Delay? While it is possible that Myriad’s offer of surrender might succeed in halting the Australian litigation before it even begins, the more likely scenario is that it will serve to delay the litigation. Indeed, that appears to have already happened: the first hearing in the Australian litigation, initially scheduled for September 1st, was recently rescheduled for October 14th. That delay is likely related to Myriad’s offer to surrender the ‘004 Patent and the statutory requirement that all offers of surrender be held open for public comment for one month following its publication in the Australian Official Journal of Patents before any ruling is made. Further delays in the Australian litigation could result if the surrender is successful and the plaintiffs are forced to file new litigation challenging one or more of Myriad’s remaining patents.

Regardless of the reason, every delay increases the likelihood that the Australian litigation will lag behind its U.S. counterpart, thereby reducing the likelihood that an unfavorable ruling in Australia could serve as an unwelcome (from Myriad’s perspective) precedent for a U.S. court. Either way, with the deadline for public comment on Myriad’s offer of surrender now passed, and upcoming court proceedings in both Australia and the U.S., it will not be long before the next chapter is written.

Here in the U.S., the gene patent litigation shows no signs of reaching a swift resolution. Over the summer, Myriad appealed March’s widely-discussed district court ruling invalidating several of its key BRCA patents and claims, and the current appeal is unlikely to be the last, regardless of the outcome. In Australia, however, Myriad appears to be taking a different tack: offering to surrender its BRCA patent.

An Offer to Surrender. The development was first reported by the Australian news program Four Corners, which earlier this month ran a program (transcript) on the gene patenting debate and its impact on the availability of genetic testing in Australia. The program concluded with the following:

Three weeks ago, lawyers acting on behalf of Myriad offered to surrender ownership of its Australian breast cancer patent. In a letter obtained by Four Corners, the company stated:

‘Myriad wishes to gift Australian Patent No 686004 [the ‘004 Patent] to the people of Australia.’

Myriad’s critics argue it’s a cynical ploy to kill of [sic] any legal challenge in Australia which could bolster the New York court decision.

Significantly the company pointed out:

‘Myriad’s offer does not constitute an admission that the [‘004 Patent] is invalid.’

In the twists and turns of the genes war, the battle is far from over.

While the GLR has been unable to locate a complete copy of the letter, Myriad has filed with the Australian Official Journal of Patents an “offer to surrender” the ‘004 Patent, which claims “in vivo mutations and polymorphisms in the 17q-linked breast and ovarian susceptibility gene” (pdf).

The main claims in the ’004 Patent (pdf) largely track those of Myriads’ BRCA-1 patents that are at the core of the U.S. litigation. The primary difference is that the Australian patent’s claims are not directed at the normal BRCA-1 gene, but at a set of “bad” mutant or polymorphic versions of that gene. Despite this difference, the Australian claims still appear to be valuable for purposes of BRCA diagnostic testing.

Will Myriad’s Surrender be Accepted? Pursuant to Chapter 12, Section 137 of the Australian Patent Act, the Commissioner of Patents may accept an offer to surrender a patent from a patentee (i) “after hearing from all interested persons who…wish to be heard” regarding the proposed matter and, (ii) “where relevant proceedings in relation to a patent are pending,” only with “either the leave of the court or the consent of the parties to the proceedings.”

As in the U.S., the Australian litigation is being positioned by the plaintiffs as an opportunity to argue that genes, including the BRCA genes, are “not an invention capable of patent protection.” With the plaintiffs taking the position in the press that patenting genes is “morally wrong,” it seems reasonably likely that the plaintiffs might object to Myriad’s patent surrender, at least to the extent it moots some or all of their claims.

What about the Rest of Myriad’s Portfolio? Given that Myriad’s notice of surrender refers solely to the ‘004 Patent, the Australian litigation may go forward irrespective of whether Myriad’s surrender is successful. The company is also listed as either the sole patentee or a co-patentee on several related patents, including patents for a “method for diagnosing a predisposition for breast and ovarian cancer” (pdf) or for a “17q-linked breast and ovarian cancer susceptibility gene” (pdf).

These patents bear substantial similarities to those at issue in the U.S. litigation, and it is unclear – and seemingly doubtful – whether the surrender of the ‘004 Patent would materially impair Myriad’s (or its licensee’s) ability to control the market for BRCA testing in Australia.

What Happened to GTL? As we discussed in our earlier post, in 2002 Myriad granted an exclusive license to perform diagnostic testing in Australia and New Zealand of the BRCA-1 and BRCA-2 genes to Genetic Technologies Limited (“GTL”). (We note that GTL is not identified as a licensee of the ‘004 Patent or of the other breast cancer-related patents identified in the IP Australia database, although GTL has publicly discussed its exclusive license.)

According to reports, when GTL first licensed the BRCA intellectual property from Myriad, the company announced that it would refrain from enforcing its rights as a “gift to the people of Australia and New Zealand.” GTL briefly changed that policy in 2008, announcing a “commercial decision to enforce the rights granted to it under an exclusive license from Myriad.” GTL sent warning letters to government testing laboratories around Australia, only to quickly back off in response to substantial public outcry.

But as Myriad attempts to gift at least one of its BRCA patents back to the people of Australia and New Zealand, what are GTL’s rights and what, if anything, does it think of Myriad’s decision?

In a very brief op-ed earlier this year in The Australian, GTL’s CEO, Paul MacLeman, clarified that, contrary to popular belief:

In fact, [GTL] would materially benefit from any scaling back of genetic patent rights in this area, as we are the only entity paying for the right to use it even though the test is quite widely used.”

In light of this, it is possible that GTL and Myriad have taken steps to terminate the BRCA license. Or it may be that the license never applied to the ‘004 Patent at all.

Both scenarios are pure speculation, and neither explain Myriad’s apparent decision to pull back on only a portion of its Australian patent portfolio. For the moment, we do not know nearly enough about the rationale behind Myriad’s decision to attempt to surrender the ‘004 Patent while retaining its other patents.

What Does this Mean for Myriad in the U.S.? The simple answer is very little, particularly for the moment. As we wrote when the Australian litigation was first announced, the status of Myriad’s or any other party’s Australian patents is unlikely to have any direct bearing on the validity of Myriad’s U.S. patents. There has been some speculation, including by Four Corners, that Myriad’s patent surrender is a defensive gesture meant to “kill of [sic] any legal challenge in Australia which could bolster the [U.S. district court ruling].” However, given the differences in Australian and U.S. patent law, as well as the likelihood that the Australian litigation will proceed despite Myriad’s attempted surrender of the ’004 Patent, this seems an unlikely – and at any rate, likely unsuccessful – strategy for Myriad to pursue.

Still, the Myriad gene patent litigation is about more than any specific set of patents or claims. It is an attempt, particularly by the plaintiffs in both the U.S. and Australia, to put the patentability of genetic information and associations on trial in the court of public opinion as well as in the courtroom. So perhaps Myriad’s decision is nothing more than a somewhat puzzling attempt at public relations maneuvering.

As we wrote in June when the Australian litigation was first announced:

…the new Australian case will be, at a minimum, a chance for that country to engage in a public debate over the wisdom and legality of patenting genes—which is exactly what is happening in the United States as a result of the ACLU litigation.

As the debate over the patentability of genes continues to rage on, its effects will be felt in the form of high-profile government investigations (e.g., the SACGHS gene patent and licensing report and the Australian Senate’s similar investigation), more closely observed and contested patent proceedings and myriad other ways beyond the courtroom, in the United States, Australia and around the world.

[Editor’s Note:

On Tuesday, Carmichael and five commentators examined what can be learned from a DTC genetic test. Yesterday, the topic was whether DTC genetic tests are trustworthy, and whether the results can be cause for concern. Today’s topic is the regulation of DTC genetic tests. In addition to several short commentaries, including a much shorter version of the piece below, Carmichael has also posted a lengthy interview with two top FDA officials on the subject of DTC genetic testing regulation.

The column below is an expanded version of what appears over at Newsweek. To see all of the commentaries in Carmichael’s series, click here.]

The recent media attention focused on direct-to-consumer (DTC) genetic tests has left companies, investors, consumers and even regulators scrambling to figure out what comes next.

As the situation stands today, companies and their investors live in a climate of unprecedented regulatory uncertainty, causing delays in the introduction of new products and rendering an already inhospitable economic climate – for both fundraising and sales – even more challenging. Commentators and regulators caution consumers that some DTC genetic tests may be unreliable or, worse, harmful, but have yet to provide clear tools and guidelines for evaluating competing tests. And regulators, including the FDA, must balance their mandate to protect the health and safety of the public with that same public’s desire for autonomy, while also recognizing that innovation is a prerequisite for a healthcare system that must continue to improve outcomes while reducing costs.

Clearly, something must change. But what will that change be? And how will the field of DTC genetic testing evolve? Will DTC be able to continue its current business while regulators and companies engage in protracted negotiations? Will oversight weed out the “snake oil salesmen” and permit legitimate companies to flourish? Will it drive all genetic testing (temporarily) out of the hands of consumers?

Or will the field change in a dramatic and completely unexpected way?

These questions, and others, caused Newsweek science editor Mary Carmichael to realize her oft-debated question – To Test or Not To Test? – might demand an answer sooner rather than later:

. . . I started to worry . . . . How much time did I even have left to decide whether I was going to take a test myself? Even before [last month’s Congressional] hearing, the FDA had announced its plans to regulate all DTC genetic tests, possibly so heavily as to keep them off the market; the hearing was just the sort of thing that could push it to move faster. What if, by the time I finally decided if I wanted one of these tests, I couldn’t buy one anymore?

Setting aside the question of whether Carmichael, or anybody else, should buy a genetic test, this column examines the history of DTC genetic testing regulation in the United States¹ and, in the final section, whether the DTC option is likely to persist in the future.

Because this post is longer than usual, here is a quick, clickable roadmap to its various sections. If you’re already familiar with the history of DTC genetic testing you may wish to jump ahead to the final section or two.

1. 2006: DTC and the First GAO Report.

2. 2007: The Beginning of Modern DTC

3. 2008: SACGHS and a Scare From the States

4. 2009: All Quiet on the DTC Front

5. 2010: DTC Goes to Washington

6. Today: Uncertainty Reigns

7. Tomorrow: Unintended Effects (and More Uncertainty)

8. Beyond: A Delicate Balancing Act

2006: DTC and the First GAO Report. Four years ago last month, the Federal Trade Commission (FTC), Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) published a consumer fact sheet entitled “At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription.” The guidance warned consumers to be wary of claims made by DTC genetic testing companies and to involve “a doctor or trained counselor who understands the value of genetic testing for a particular situation” when ordering or interpreting any genetic test.

The joint agency guidance document was published in concert with a report from the Government Accountability Office (GAO) entitled “Nutrigenetic Testing: Tests Purchased from Four Web Sites Mislead Consumers” (pdf). The GAO report reviewed a “nonrepresentative selection” of genetic tests available to consumers at that time and concluded that those tests “mislead the consumer by making health-related predictions that are medically unproven and so ambiguous that they do not provide meaningful information to consumers.” The report was praised for “drawing attention to potentially important consumer protection issues,” even as it was criticized for “serious methodological flaws that undermine[d]” those very criticisms (pdf).

Whatever its methodological flaws, the GAO’s description of the system of regulation for DTC genetic testing, which it characterized as one of “minimal oversight [that] makes it difficult for consumers to determine whether a genetic test provides meaningful, scientifically based information,” was entirely accurate.

2007: The Beginning of Modern DTC. With the launch of DTC products from a publicly traded biopharmaceutical company (deCODE Genetics) and a Google-backed startup (23andMe) on back-to-back days in November 2007, the modern era of DTC genetic testing was born. With 23andMe, deCODE and, soon, Navigenics, consumers could now pay around $1,000 to review hundreds of thousands of SNPs. Following Knome’s launch, also late in 2007, they could pay much, much more ($350,000) for access to their entire genome.

Despite this dramatic shift in the DTC product landscape, the legal landscape remained essentially unchanged from 2006. Regulatory oversight was still incomplete, confusing and rarely invoked.

At the federal level, while most DTC genetic tests were likely covered from the outset by the Clinical Laboratory Improvement Amendments of 1988 (CLIA), it was typically difficult to determine whether DTC genetic testing companies were operating using CLIA-certified labs. (23andMe, for example, did not begin using a CLIA-certified laboratory until 2008, making the change in response to “evolving” regulatory requirements.) CLIA, which is implemented by the Centers for Medicare & Medicaid Services (CMS), requires laboratories to demonstrate the analytical validity of their tests, and covers most genetic tests regardless of whether they are provided directly to consumers or not.

In addition to CLIA, a limited number of genetic tests were also regulated by the FDA. Although the proposition was not immediately tested, it was widely assumed that DTC genetic tests constituted a new form of laboratory developed test (LDT), a large and well-established category of tests over which the FDA exercised “enforcement discretion.” While the FDA had historically declined to regulate LDTs, in 2006 and 2007 the FDA expressed its desire to regulate certain types of high-complexity LDTs (so-called IVDMIAs). As is still true today, it was unclear where, if anywhere, the newly introduced DTC genetic tests fell within the LDT conversation and FDA’s larger regulatory universe.

In addition to uncertainty at the federal level, some states possessed (and still do possess) statutes that appear to prohibit – or at least restrict – DTC genetic testing (pdf). However, it was unclear whether such statutes, which clearly predate the arrival of DTC genetic testing in its current form, were intended to prevent DTC genetic testing or whether they would be enforced by state regulators in any event. State-level regulatory restrictions contributed to at least one company withholding its service from citizens in at least 10 states at the time of its launch.

Despite all of this legal uncertainty, no federal or state regulatory agency took any formal action immediately following the introduction of DTC genetic testing to the consumer marketplace.

2008: SACGHS and A Scare from the States. During its first full year, the DTC genetic testing marketplace continued to grow as new companies arrived on the scene and existing companies refined and expanded their offerings.

Meanwhile, an influential government policy committee (SACGHS) had undertaken a review of the “U.S. System of Oversight of Genetic Testing.” When it was published in April of 2008, the 276-page report surprised almost no one when it identified major gaps in the regulation of genetic testing, including insufficient oversight of laboratory quality, clinical validity and a lack of knowledge with respect to the nature and uses of genetic tests available for purchase, whether directly by consumers or otherwise. Among the report’s several recommendations were increased FDA regulatory oversight and the creation of a mandatory, public registry for all laboratory tests.

Shortly after the publication of the SACGHS report, public health officials in New York and California sent “cease and desist” letters to a number of genetic testing companies. The states warned the companies – including 23andMe, deCODE and Navigenics, the three most prominent DTC providers at that time – that they were operating without necessary state licenses.

The SACGHS report and state regulatory letters produced widespread debate about the appropriate regulatory framework for DTC genetic testing. Companies were concerned that other states might follow the example set by New York and California and seek to regulate DTC genetic tests directly, potentially exposing DTC companies to a nightmare scenario of inconsistent, state-by-state regulation. Proponents of regulation, meanwhile, argued that the nascent field needed some regulation “lest abuses discredit the whole industry before it has a chance to thrive.”

In the following weeks, months and even years, some DTC companies received state licenses, although this came at the expense of offering tests directly to consumers in some cases. Other companies ceased selling to customers in specific jurisdictions, and still others simply went out of business. At the federal level, the SACGHS recommendations continued to generate far more discussion than action, and the regulatory landscape remained materially unchanged. Meanwhile, major DTC companies continued to press ahead, and 2008 closed with 23andMe’s DTC genetic test being named Time’s invention of the year.

2009: All Quiet on the DTC Front. In comparison to the years on either side, 2009 was a relatively quiet year for DTC genetic testing, at least from a regulatory perspective.

On the commercial side, however, 2009 saw a number of changes ripple through the DTC genetic testing marketplace. As the price of DTC genetic tests continued to fall, a new competitor, Pathway Genomics, arrived on the scene and 23andMe significantly revamped its product offerings and pricing shortly thereafter. Meanwhile, the financial crisis played a major role in causing DTC pioneer deCODE Genetics to file for bankruptcy protection, although the company quickly emerged under private control and its deCODEme test remains on the market today.

To be sure, regulators continued to ponder how to respond to the rapidly evolving genetic testing marketplace, which included but was not limited to DTC products. For example, the FDA continued to express an interest in regulating some LDTs and the California legislature considered a bill – championed by 23andMe – that would create a special regulatory framework for so-called “post-CLIA bioinformatics services,” although nothing would come of either initiative, at least in 2009. Perhaps most significantly, but unbeknownst to either the public or the major DTC genetic testing companies, Congress had instructed the GAO to begin a second investigation into the DTC genetic testing industry, the results of which would not be made public until the following year.

With regulators seemingly on the sidelines, academics and other commentators, including the Genomics Law Report, continued to stress the need for meaningful self-regulation in order to:

(1) discourag[e] consumers from purchasing products not adequately supported by scientific evidence, (2) provid[e] regulators such as the Federal Trade Commission (FTC) with a standard against which to evaluate (and sanction) false or misleading DTC tests or services, and (3) ensur[e] that inevitable governmental regulation is not overly restrictive.

Prominent scientists, including soon-to-be NIH chief Francis Collins and genomics pioneer Craig Venter, also emphasized the need for greater transparency and consistency in the way DTC companies presented genetic risk of disease to consumers. While there was widespread consensus, including on the part of DTC providers, that self-regulation and even some form of government regulation would be beneficial for the industry as a whole, by the end of 2009 no notable changes – government mandated, voluntary or otherwise – had materialized.

2010: DTC Goes to Washington. Although we are not yet two thirds of the way through the year, 2010 has already seen an explosion of activity in the oversight of DTC genetic testing.

The first major development came in March, when the NIH announced the creation of a voluntary genetic testing registry. In its 2008 report (pdf), SACGHS had recommended the creation of a “mandatory, publicly available, Web-based registry for laboratory tests” in order to “enhance the transparency of genetic testing and assist efforts in reviewing the clinical validity of laboratory tests.” The NIH adopted this recommendation with one crucial exception: the registry, at least as proposed, will be voluntary.  However, it remains to be seen, particularly in light of everything that has happened since the announcement in March, what form the NIH’s registry will ultimately take when it debuts later this year or in early 2011.

For DTC genetic testing, the excitement really began on May 11th, when Pathway Genomics announced it was partnering with Walgreens to offer its genetic testing service on the shelves of most of the drugstore giant’s 7,500 stores. The FDA responded almost immediately with an “Untitled Agency” letter to Pathway Genomics in which the agency informed Pathway that it could find no record of the necessary FDA clearance or approval for Pathway’s test. The Pathway letter – which represented the FDA’s first public foray into the oversight of DTC genetic testing – was followed by similar letters to five prominent DTC genetic testing companies in early June and letters to 14 more genetic testing companies in late July. These letters were, of course, something of a surprise to the companies. The FDA could not find evidence that it had approved the companies’ tests because, in at least some and possibly all cases, the agency had not told the companies that such approval was necessary.

In addition to taking aim at DTC genetic testing companies, the FDA also announced that it was shelving its plan to regulate a subset of LDTs (i.e., IVDMIAs) in favor of a new plan to regulate all LDTs. Late last month the FDA held a two-day “Public Meeting on Oversight of Laboratory Developed Tests” to discuss that plan. (It is important to point out that, despite devoting an entire portion of the public meeting to DTC genetic tests, on multiple occasions the FDA has indicated that it considers at least some DTC genetic tests not to constitute LDTs since the products are “not developed by and used in a single laboratory.”)

Not to be outdone, Congress quickly announced its own investigation into DTC genetic testing (one it had quietly initiated the year before) and followed that up with a public hearing on “Direct-To-Consumer Genetic Testing and the Consequences to Public Health.” The centerpiece of July’s Congressional hearing was yet another GAO report (pdf) whose conclusion was announced in the title: “Direct-To-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices.” The GAO also presented a striking and widely circulated YouTube video as partial support for its conclusion. (For a more detailed review of the Congressional hearing and the GAO report please see this recap.)

At the Congressional hearing, Jeffrey Shuren, the Director of the FDA’s Center for Devices and Radiological Health (CDRH), assessed the FDA’s recent activity by agreeing with Congressman Michael Burgess (R-TX) that the FDA “should have acted sooner” to regulate DTC genetic tests. Shuren was likely referring to a perceived failure on the part of the FDA to adequately safeguard the public.  Given the absence of any publicly documented harm resulting from consumer access to genetic tests , however, there are certainly those who would disagree, arguing that the FDA should still refrain from regulating DTC genetic tests.

Listening to Shuren’s remarks at the hearing, one could easily wonder whether his lament was actually directed at the agency having been caught off-guard, at least to a degree, by the debut of the GAO’s striking report, which was unveiled to the public – and the DTC companies themselves – at the hearing.  According to the report (pg. 19) the GAO officially briefed the FDA, NIH and FTC on the contents of the report in late May and early June. However, when I raised this point yesterday during an FDLI webinar on FDA’s (Emerging) Oversight of LDTs, fellow panelist Dr. Elisabeth Mansfield, Director for Personalized Medicine at CDRH, clarified that the GAO’s “briefing” consisted of a teleconference where the FDA learned only the bare fact that the GAO had conducted an inspection and had “found problems.”

Perhaps it is just a perfect storm of coincidences. But in any event, the FDA actions and the GAO report – along with other recent high-profile developments including the Pathway / Walgreens pairing and 23andMe’s “sample swap” – have created unprecedented uncertainty.

Today: Uncertainty Reigns. The GAO report, the FDA’s letters and all of the other events of the past few months have indisputably ratcheted up the level of uncertainty throughout the genetic testing industry.

However, as a purely legal matter, it does not appear that the formal regulatory framework governing DTC genetic testing has changed much if at all in recent months, or even since 2006, particularly at the federal level. Congress has passed no new legislation, and neither the FDA nor any other federal agency has promulgated new regulations or formal agency guidance.   This, of course, is not at all surprising: the rate of development in any new area of science and commerce inevitably surpasses the ability of lawmakers and regulators to keep pace. DTC genetic testing has hardly proved an exception to that rule.

Setting aside the myriad hearings, public and private meetings and statements made to the press by regulators – which, while significant, do not rise to the level of rulemaking – the only formal, public action one can point to is the FDA’s ongoing letter-writing campaign. However, as the FDA has clarified in the past, these “Untitled Letters” remain several steps removed from an FDA enforcement action:

While Warning Letters set out specific violations of law that a company must address immediately or else the agency will take an enforcement action, an Untitled Letter identifies agency concerns and gives a company the opportunity to meet with the agency and to have time to take appropriate steps to address these concerns….Based on how the companies respond to the Untitled Letters, FDA may follow up by sending Warning Letters.

Of course, an absence of documented regulatory change does not imply that the commercial DTC genetic testing landscape has remained anything close to stable.

Responses from DTC companies and investors to today’s uncertainty have varied. Some companies (including Pathway Genomics and Counsyl) have ceased offering their tests directly to consumers, at least for the moment. Others, including two original DTC genetic testing companies (23andMe and deCODE), have expressed a desire to work with regulators while continuing to make their products available to consumers. Many of the major DTC companies, whether or not they are currently offering products directly to consumers, have also criticized both the GAO and the FDA for their approach to DTC genetic testing (see these blog posts at Navigenics, 23andMe and Pathway Genomics) while simultaneously expressing their desire to work with regulators to bring greater oversight to the industry.

Meanwhile, new companies and investors must reevaluate business plans to take into account anticipated regulatory changes.  And customers, including Mary Carmichael, must weigh the possibility that today’s DTC options may disappear from tomorrow’s digital storefronts.

Since 2006, the regulation of DTC genetic testing has been consistently characterized as confusing, incomplete and inconsistently applied. That characterization remains as true today as it was four years ago. So perhaps the only meaningful difference from four years ago is one of degree: more so than at any time over the past four years, there now appears to be a consensus that something must – and will – be done to overhaul the regulation of DTC genetic tests.

Tomorrow: Unintended Effects (and More Uncertainty). But not so fast. Despite the apparent agreement among regulators, industry and most commentators that DTC genetic testing is in need of additional oversight, there is still no guarantee that change is coming soon, or even at all.

Indeed, it is not difficult to look at the events of the past few months and conclude that DTC has been down this road before:

• A GAO report decrying the evils of DTC genetic testing and subsequent Congressional hearing? 2010 and 2006.
• Threatening regulatory letters to DTC companies? 2010 and 2008.
• A controversial FDA regulatory proposal that might – or might not – encompass DTC genetic tests? 2010 and 2006.

Industry watchers who have been around since the beginning would be excused for expressing at least some skepticism that this is the time, finally, when the DTC genetic testing landscape will be fundamentally remade.

Continuing Uncertainty. There is also the possibility that a new regulatory regime for genetic tests will emerge, but that it will push DTC genetic testing to the side and in so doing cause the industry to remain mired in uncertainty.

As the FDA pushes forward with the development of agency guidance for the regulation of LDTs, there are concerns that the agency may carve out many or most DTC genetic tests from this regulatory framework. In June, the FDA expressed its belief that several prominent DTC companies (23andMe, Knome and deCode) are offering tests that do not constitute LDTs because they are “not developed by and used in a single laboratory.”

Recent signals – including the designation of a separate panel for LDTs during the FDA’s two-day public meeting and Jeffrey Shuren’s presentation of DTC genetic tests within the confines of the larger LDT regulatory conversation (pdf) at the recent Congressional hearing – suggest that the FDA may yet find a way to incorporate the regulation of DTC genetic tests into its more ambitious plan to develop a risk-based approach for all LDTs. But for the moment, the FDA appears to be intent on continuing with test-by-test review and regulation.

Unintended Effects. Among its several shortcomings, the current test-by-test approach to DTC genetic testing regulation creates the possibility that a regulatory agency such as the FDA could seek to reshape the industry using indirect methods.

When the FDA sent out its first batch of letters post-Pathway, the one unexpected recipient was array manufacturer Illumina, which, unlike the other companies receiving letters, does not appear to have ever offered its services directly to consumers without the involvement of a physician intermediary. Nor did the FDA allege that it had. Instead, the FDA’s letter to Illumina (pdf) focused on the company’s “Infinium HumanHap550 array used by deCODE Genetics and 23andMe to provide genetic information to their customers.” The FDA charged Illumina with making available an array approved for “Research Use Only” to 23andMe and deCode for use in their own DTC genetic tests.

Why does this matter? As I wrote at the time, not every company has the same set of incentives to resist the FDA’s regulatory proposals. Whereas a company such as 23andMe, which has built its business around DTC genetic testing, has a clear interest in challenging any FDA action that results in its service becoming unavailable to consumers, array manufacturers like Illumina are not similarly situated. As Illumina’s CEO, Jay Flatley, recently noted, the revenue the company “generates from sales of arrays to the DTC market is ‘immaterial.’” By targeting array suppliers such as Illumina, for whom DTC represents only a fraction of their business, the FDA may have identified a way to exert indirect but potentially much more effective regulatory pressure over the industry.

In response, Daniel MacArthur asked yesterday whether the FDA was planning to strangle the supply lines of DTC genetic testing companies by targeting array manufacturers like Illumina. As a regulatory agency charged with implementing legislation passed by Congress, the FDA is extremely unlikely to have an official “agenda” when it comes to DTC genetic testing. That does not mean, however, that the FDA could not determine that genetic testing simply cannot be paired with DTC and still satisfy its interpretation of the law.

If 23andMe or deCode (which is partially owned by Illumina) were to lose access to Illumina’s arrays, would those companies be able to contract with another manufacturer, either based in the U.S. or abroad? Would Illumina take the necessary steps to work with 23andMe and the FDA to clear its array for use in 23andMe’s product? Would this development force such a fundamental shift in the business models of these DTC companies that they would be driven out of business, or perhaps driven overseas?

Even as a hypothetical, the Illumina example illustrates the importance of considering the knock-on effects of regulation. Although the FDA may take the position that its goal is to enforce agency regulations regardless of the effects they produce on a specific business, or even an entire industry, the reality is that there are a number of viable regulatory strategies on the table, and not all of them are equal in their effects.

One of the unfortunate consequences of the test-by-test regulation currently employed by the FDA is that these effects are unlikely to be fully anticipated or explored in advance by regulators. By the same token, one obvious advantage of publicly pursuing a formal system of regulation for DTC genetic testing – e.g., through the development of agency guidance or notice and comment rulemaking – is that such regulatory effects can be explored in advance (in some instances this may even be required of the FDA), rendering them at least intended, even if they remain unwelcome to some.

Other Regulatory Routes. Finally, remember that the FDA may not be left entirely to its own devices in determining how to regulate either LDTs or DTC genetic tests. Several pieces of draft legislation, if enacted, could provide specific Congressional direction as to how the FDA or other regulatory agencies should respond to the challenges raised by these tests.

Current proposals include the Genomics and Personalized Medicine Act – originally introduced by then-Senator Obama and now in its fifth year on Capitol Hill – and the inelegantly named Better Evaluation and Treatment Through Essential Regulatory Reform for Patient Care Act.

The prudent approach – particularly for companies, investors and consumers with an interest in DTC genetic testing regulation – is to assume that some type of regulatory reform is coming to the industry. Unfortunately, important details like “what regulation” and “when will it arrive” continue to remain elusive.

Beyond: A Delicate Balancing Act. Assuming that lawmakers and regulators do decide to develop a formal DTC regulatory regime, the details will be a long time in coming. Stakeholder input will be crucial, and the rapidly changing scientific and commercial landscape will continue to pose a challenge for slower-moving lawmakers and regulators.

Despite all of this uncertainty, it is yet possible to identify (i) several key areas of relative consensus for any prospective DTC regulatory framework and (ii) some of the most pressing areas of dispute that must be resolved in order to proceed.

The First Step: Defining DTC. Before we get to areas of consensus and dispute, however, a brief word about definitions. Any formal regulatory framework will need to set out a clear definition of what, exactly, constitutes a “direct-to-consumer genetic test.” As the personal genomics industry has grown increasingly diverse, the application of the label “DTC” to all consumer-oriented genetic products has become increasingly untenable.

There are, at the moment, at least three different types of DTC genetic tests:

• tests marketed to consumers but ordered and interpreted by a healthcare provider;
• tests marketed to and ordered by consumers but received and interpreted by or only in the presence of a healthcare provider; and
• tests marketed to, ordered by and received by consumers without any requirement that a healthcare provider be involved (although this option is frequently made available to consumers).

While the focus has frequently been on the third and most consumer-oriented type of genetic test, not all so-called DTC genetic testing companies fall into this category. This is significant since the risks – whether hypothetical or actual – of “DTC genetic testing,” as well as the appropriate regulatory response, clearly depend in large part on what exactly is meant by that term.

Finding Common Ground. Although few in number, it appears that consensus is emerging in certain areas pertaining to DTC genetic testing.

Access to Raw Data. Even those who strongly support the robust regulation of DTC genetic testing, agree that individuals should have the right to directly access their raw genetic data (pdf). In public and private comments, the FDA has appeared to embrace this position as well, indicating it is medical claims or interpretations – and not genetic information per se – that concerns the agency.

We need to be careful, however, to define exactly what this outbreak of agreement covers. Although important for what it says about an individual’s right to access their own genome, it likely refers only to the most basic level of access – a large file of As, Cs, Ts and Gs – and to nothing more. This is only a first step. Meaningful “access” for the vast majority of individuals begins only with the ability to access interpreted data.

Registration and Truth in Advertising. As the recent GAO report laid plain, there is a clear need for more robust regulation of the advertising and marketing practices of existing genetic testing companies, including DTC companies, to ensure consumers are not being intentionally or even accidentally misled.

Addressing this issue requires a thorough understanding of the tests currently offered to consumers, including how they are marketed or advertised, how they are intended to be used, and how they are actually used. The FDA has acknowledged several times in public discussions, including yesterday, that the agency lacks this information and that it would be useful in developing appropriate regulations.

While there remains some disagreement over the proper agency or agencies to collect this information and to take appropriate enforcement actions where necessary (the FDA and the FTC have both demonstrated some interest, and the NIH is currently developing a genetic testing registry), there is widespread agreement that these steps should be taken, and soon.

Industry-Wide Standards. Finally, almost since the inception of DTC genetic testing in 2007, there has been a widespread recognition that the industry would benefit from a more standardized approach to interpreting and reporting genetic data.

Early efforts led by the Personalized Medicine Coalition to produce industry-developed standards have stalled, but the inconsistency demonstrated by Collins, Venter et al. and most recently the GAO report have resulted in renewed interest from industry and regulators in addressing this issue.

Here, again, it is important to acknowledge the limited scope of this consensus. There is real agreement that standards are needed. The development and application of those standards, however, raises a host of questions, some of which are discussed below, to which there are hardly consensus answers.

Resolving Disputes. Beyond the few but important areas of consensus described above, it is certain that any emerging regulatory framework will have to tackle numerous difficult questions about which there is a decided lack of agreement. While it is impossible to list all of the areas of disagreement, some of the most pressing issues are:

• whether genetic tests should ever be offered directly to consumers without the involvement of a trained intermediary such as a physician or genetic counselor (i.e., should the third type of DTC genetic testing described above disappear);
• whether to create separate standards for non-clinical genetic tests, including genetic ancestry testing, and how to appropriately define the line between clinical and non-clinical tests;
• how to regulate genetic tests or products that include a large number of interpretations and claims in light of the need to constantly update those claims to best reflect current scientific understanding;
• whether clinical utility, or lack thereof, should be included in determining whether a particular genetic test or association is made available, whether DTC or otherwise;
• how to regulate interpretative tools that do not involve any new testing, but simply offer additional interpretations of raw genetic data already in a consumer’s possession;
• how to address the role of preliminary scientific findings and research in the development of interpretive tools, including genetic tests; and
• whether to focus regulatory efforts on pre-test measures that restrict the availability of potentially harmful genetic tests or post-test initiatives designed to evaluate how consumers perceive, use and react to genetic tests.

The answers to these questions and others, as well as the role industry, consumers and healthcare providers are permitted to play in the conversation, will determine the substance of any forthcoming DTC regulatory framework.

Answering Mary’s Question: To Test or Not To Test? While tomorrow always carries the possibility of a new and clearer day for the regulation of DTC genetic testing, the reality is that, for the moment, all we can say for sure is that the conversation is continuing. What was true in 2006 is still true today: genetic tests are available for purchase directly by consumers, and the regulatory requirements imposed on the companies that offer those tests are unclear and seemingly poised to shift at a moment’s notice.

As I have written several times before, I am optimistic about the long-term prospects for personal genomics in the United States, including DTC genetic testing. As the underlying technology and science continue to improve, the price and value of individual-level genomic data will continue to move in opposite directions, generating increased demand. In time, as increasing demand leads to increasing accessibility and, ultimately, to increasing familiarity – on the part of both consumers and regulators – the development of a tailored system of oversight that permits direct access while adequately protecting consumer safety and ensuring the accuracy and validity of DTC products can be developed.

But none of this will happen overnight. For all of our own interest, DTC genetic testing remains decidedly a niche phenomenon, and the industry poses novel and difficult challenges to regulators. It will take time for these to be ironed out and, in the short-term, it is possible that DTC genetic testing will be presented with a substantially more restrictive regulatory framework than at present.

Ultimately, while I cannot advise Mary Carmichael as to whether she should or should not go through with a DTC genetic test – that’s a personal decision – I can say that if she decides to proceed there is no time like today, for there is no guarantee that the option will still be on the table tomorrow.

_______________

¹The regulation of DTC genetic testing is far from uniform at the international level. Some countries, including Germany, appear to have effectively legislated DTC genetic testing out of existence, at least for the time being. Elsewhere, most notably the U.K., the conversation remains at the level of voluntary guidelines instead of formal – or even informal – regulation. Recent examples include the 2009 House of Lords report on genomic medicine and yesterday’s publication by the Human Genetics Commission of “A Common Framework of Principles for direct-to-consumer genetic testing services” (pdf).

The factual background in Australia seems a bit different. Myriad has granted an exclusive license to perform BRCA gene tests to a Melbourne company called Genetic Technologies Limited, which is a co-defendant in the case. But GTL has been reported to have “gifted” its patent rights to health care institutions, and not to charge royalties. Nonetheless, the plaintiffs’ lawyers have expressed concern about the possibility of GTL exploiting their monopoly as in the U.S., where the tests cost over $3,000. They note that on two earlier occasions GTL sent letters to hospitals telling them to stop testing. A number of Australian sources have also worried aloud about the implications of the patents for medical research.

In a technical sense, the case will have no direct effects outside of Australia. The general principle of international patent law is “non-extraterritoriality”—a jaw-breaker that means simply that a patent is enforceable only within the boundaries of the country that issues it. So even if the Australian courts ultimately invalidate the Myriad patents, that will not affect their status anywhere else. Plaintiffs who want to challenge the patents will have to do so country-by-country.

But as is so often the case with legal issues (fortunately for lawyers, and unfortunately for their clients), the situation is more complicated on a practical level. First, there is a partial exception to the country-by-country rule: the European Patent Office in Munich. There is still no such thing as a true “European patent” (the European Union has been working on it for years), but the EPO will examine applications under a single standard for patentability (established by a treaty called the European Patent Convention) and issue what it calls a “bundle” on national patents. That is, you can designate the countries in which you want your patent to be effective—say the U.K., France, and Germany—and the EPO can issue you a bundle containing a British, a French, and a German patent. Although you have to go to the individual countries to sue infringers, some challenges to the patent can be brought in the EPO. The Myriad patents have a long and complex history in the EPO, with the net result that they have a narrower scope than in the U.S.

A second point is that the Australian court system is well-regarded throughout the world, so a decision against the patents there could influence courts facing the same issue elsewhere—even though it wouldn’t bind them. Even the U.S. Supreme Court, which has long paid little or no attention to foreign precedent, has been citing foreign legal authorities more frequently in recent years.

The final point relates to the potential business strategy of competitors of companies like Myriad. Assume that a U.S. company wants to include genes patented by others (Myriad or someone else) in a broad-based diagnostic testing program. One approach would be to seek a license from the patent-holder. But there is an alternative: do the testing in a country that doesn’t recognize the patent. U.S. patent law (like that of almost every country) forbids making, using, or selling the patented invention within the U.S. There are some circumstances in which U.S. law can reach foreign activities (such as when the infringer sells parts of the invention from the U.S. to be assembled abroad), but under the present state of the law it would probably not be infringement to test patented genes abroad and send the results back to the U.S. The more countries that invalidate the patent, the more places there are to execute this strategy.

So the new Australian case will be, at a minimum, a chance for that country to engage in a public debate over the wisdom and legality of patenting genes—which is exactly what is happening in the United States as a result of the ACLU litigation. But in the long term it could serve to undercut the practical value of gene patents everywhere.

Why? Until today, the FDA’s recent announcements have involved a series of letters to DTC genetic testing companies, beginning last month with Pathway Genomics and continuing last week with letters to five other prominent DTC companies. Despite all of the attention paid to these letters, the sum total of the FDA’s regulatory focus amounted to only a handful of products. Today’s announcement, on the other hand, declares the FDA’s intent to much more aggressively regulate the entire field of LDTs. While an exact count of the number of LDTs available is impossible, GeneTests.org lists more than 2,000 genetic tests from nearly 600 laboratories, numbers which do not even include genetic tests and other diagnostic products offered DTC. After having been criticized for a policy of case-by-case regulation, the FDA has answered with a move to regulate the entire field of laboratory-based testing.

Why the FDA is Regulating LDTs. The FDA’s notice of public meeting and request for comments (pdf) provides a roadmap for how the agency came to the conclusion that it must begin to more actively regulate LDTs. (For more on the FDA’s current regulation of LDTs see here and here.) According to the agency (pdf), LDTs were initially “relatively simple, well-understood” diagnostic tests “intended to be used by physicians and pathologists within a single institution in which both were actively part of patient care.” Components of the test were generally regulated by the FDA, either as analyte specific reagents or as general reagents, and the tests were performed in CLIA laboratories certified to perform high-complexity testing.

While most LDTs are still performed in high-complexity CLIA laboratories, according to the FDA, over the past two decades the other characteristic elements of LDTs have all changed. Today’s tests are “often used to assess high-risk but relatively common diseases…and to inform critical treatment decisions” and are “often performed in geographically distant commercial laboratories instead of within the patient’s health care setting under the supervision of a patient’s pathologist and treating physician, or may be marketed directly to consumers.”

Furthermore, the FDA alleges that LDTs are now manufactured increasingly by “corporations rather than hospitals or public health laboratories, which represent a significant shift in the types of tests developed and the business model for developing them.” In language reminiscent of Genentech’s 2008 petition urging the FDA to regulate LDTs, the FDA also points out that the agency’s regulation of genetic test kits, but not LDTs, has produced an uneven playing field and created “a competitive disadvantage and potential disincentive to innovation” by test kit manufacturers.

In addition to the changes in the complexity, development and usage of LDTs, the FDA notes that “diagnostic tests are playing an increasingly important role in clinical decisionmaking and disease management, particularly in the context of personalized medicine.” The increased prominence of LDTs has increased the risks associated with tests “that have not been properly validated for their intended use.” These risks include “missed diagnosis, wrong diagnosis, and failure to receive appropriate treatment.” Ultimately, the FDA believes that “the public must be assured that the tests used in the provision of health care, whether developed by a laboratory or other manufacturer, are safe and effective.” Clearly, the FDA does not think the current regulatory regime accomplishes this goal.

How the FDA Intends to Regulate LDTs. In light of these concerns, the FDA “believes it is time to reconsider its policy of enforcement discretion over LDTs.” (For more on the agency’s “enforcement discretion” policy see here and here.) To ensure the safety and efficacy of LDTs, the FDA “believes that a risk-based application of oversight to LDTs is the appropriate approach.”

Just what, exactly, a “risk-based application of oversight” entails is unclear. The agency still needs to develop those details and, indeed, the primary purpose of the FDA’s notice is to solicit public comment from stakeholders interested in assisting the FDA in devising its LDT regulatory policy. (A secondary purpose, no doubt, is to avoid challenges to the FDA’s regulatory overhaul based on the Administrative Procedure Act (APA), an issue I discussed yesterday.)

It will be months before the details become clear, but the FDA’s top priority appears to be ensuring the safety and efficacy of LDTs. However, regulated parties will be relieved to note that the FDA has acknowledged its responsibility to “provide a reasonable, predictable, and consistent regulatory policy” that will “encourage innovation, improve patient outcomes, strengthen patient confidence in the reliability of [LDTs], and help reduce health care costs.” The agency has also indicated that it “intends to phase in [its LDT regulatory] framework over time based on the level of risk of the test.”

After failing to reach a decision on the regulation of IVDMIAs in 2007, and after delivering a series of regulatory letters aimed at individual DTC companies over the past several weeks, the FDA now appears to be gearing up for its most ambitious regulatory move yet within the burgeoning field of diagnostic testing. In the abstract, at least, the agency has presented a balanced understanding of the benefits and costs of LDT regulation, acknowledging explicitly that regulations meant to ensure safety and efficacy can threaten the innovation and commercialization of diagnostic tests essential to improving health care in the United States.

The devil, however, remains in the details. At next month’s meeting in Rockville, MD, the FDA will begin the process of balancing these competing considerations. Whether the agency will ultimately do so in a way that satisfies its safety and efficacy concerns, while simultaneously addressing the competing concerns of a diverse array of healthcare providers, patients and consumers, and companies and investors, all of whom have a significant stake in the future regulation and development of LDTs, remains to be seen.

[Update 6/17]. Turna Ray of Pharmacogenomics Reporter has confirmed that the FDA intends to shelve its IVDMIA initiative in favor of its new and much broader proposal to regulate all LDTs. “It’s possible that we will issue [an] IVDMIA guidance in the future but with this public meeting [scheduled for July], we are addressing LDTs at once in a public dialogue, instead of dealing with [them] subset by subset,” FDA spokesperson Erica Jefferson said. No surprises here. [End Update 6/17]

1. Will the $1,000 genome live up to the hype? Affordable whole-genome sequencing is coming, possibly as early as this year depending on whom you ask. But when the day inevitably arrives, after the media frenzy has subsided, will the $1,000 genome prove anti-climactic?

Whole-genome sequencing is a means to an end and not an end in itself. The understandable excitement surrounding Complete Genomics’ November announcement that it had sequenced three genomes for an average cost of $4,400 often neglected to focus on what the price tag did not cover: the substantial costs associated with interpreting the genomic data.

For genomics researchers, the falling cost of whole-genome sequencing is a continuing cause for celebration, enabling increasingly ambitious research projects. But the success of personal genomics, which is what really matters to consumers, patients and healthcare providers, requires more than inexpensive genomic data. The real breakthrough in personal genomics will come when we can offer individuals affordable access to their whole-genome sequence as well as to the genomic tools and knowledgebase necessary for those individuals to put that data to use.

2. Will personal genomics stay DTC? The marketplace for personalized medicine continues to expand—a recent report from PricewaterhouseCoopers (pdf) estimated “the size of the global market for genetic testing at $730 million, with a 20% annual growth rate”—but the commercial landscape remains a fragmented work in progress, with some well-publicized struggles in the DTC space.

Will companies that offer direct-to-consumer (DTC) genomic services prove commercially viable by encouraging consumers to treat healthcare, including genomics, as an increasingly participatory activity? Or will personal genomics—whether due to financial or regulatory forces—become more closely integrated into existing healthcare structures, with traditional medical gatekeepers (i.e., doctors and insurers) serving as intermediaries between most individuals and their genomic information?

3. How will the ongoing gene patent debate affect the progress of personalized medicine? The patentability of genes has been a disputed topic for years, and 2009 saw the debate reach new heights with a highly publicized lawsuit against Myriad Genetics spearheaded by the ACLU that will continue to continue to wend its way through the courts throughout the year. With multiple appeals expected there is little reason to believe that 2010 will be the year that the gene patent question will be finally resolved.

Still, 2010 seems likely to be an important year for defining the relationship between patents and personalized medicine technologies. The Supreme Court heard oral arguments in In re Bilski late in 2009, and its decision in that case—as well as developments in other cases, including Prometheus Laboratories, Inc. v. Mayo Collaborative—could significantly impact the patentability of diagnostic methods or processes, which are viewed by many companies and investors as a core component of the personalized medicine marketplace.

Serving as a backdrop to this ongoing patent litigation is the possibility of policy or legislative reform. Last fall a government task force on Gene Patents and Licensing recommended substantial statutory and policy changes in the biotechnology patent regime, including exempting certain treatment and research activities from patent infringement liability. More recently, Congress appears to be closing in on a health care reform bill that would provide a regulatory approval pathway for biosimilars in exchange for a period of market exclusivity (up to 12.5 years in the current House and Senate proposals) that is similar to patent protection.

The availability and enforceability of patent protection is a critical consideration for researchers, entrepreneurs, investors and, ultimately, consumers and patients in the personalized medicine space. Though the gene patent debate may grab the most headlines, it is only one piece of a much larger, ongoing conversation that will merit close attention throughout 2010.

4. When and where will the next regulatory shoe fall? 2009 saw the Genetic Information Nondiscrimination Act (GINA) take effect, and 2010 should see Congress finally set out an approval pathway for biosimilars. What other areas are likely to see increased regulatory activity in 2010?

For the third consecutive year, one possibility is an expanded regulatory framework for laboratory developed tests (LDTs), including the subset of algorithm-based tests known as In Vitro Diagnostic Multivariate Index Assays (IVDMIAs) which form the basis of many products and services offered currently offered by genomics and personalized medicine companies. The FDA published draft guidance (pdf) for the regulation of IVDMIAs in July of 2007 but has yet to finalize its thinking. Will 2010 be the year that the FDA, in coordination with CMS, finally tackles the approval and regulation of diagnostic tests through the development of a premarket approval process, a nationwide test registry or some other means?

Another candidate for additional regulation is reproductive genetic technologies, including genetic screening. The utilization of genetic technologies in reproduction remains largely unregulated in the United States, but as costs fall and genetic technologies increasingly enter the mainstream, the policy debate over the appropriateness of these technologies is set to intensify. Increased regulatory oversight—likely beginning at the state level—is a possibility. Other potential regulatory possibilities include the direct regulation of medical genetic testing by DTC companies, a Congressional revival of the Genomics and Personalized Medicine Act (GPMA), biotechnology patent reform, and new financial regulations that could impact incentives to pursue long-term investments in genomics and personalized medicine technologies.

Regulatory developments outside the US will also be significant in 2010 as they were in 2009. Countries around the world are wrestling with a variety of new and difficult issues, and the international diversity of approaches certainly enriches the analysis.

While we wait and see where and when the next regulatory shoe will fall, 2010 will also provide us with an opportunity to watch as Congress and a host of Federal agencies set to the task of implementing recently enacted legislation, including GINA, which was passed in 2008 but continues to await final regulatory guidance and will remain a work in progress as employers, insurers and individuals all try to adjust to the new law.

5. Who will control the data? If 2010 does prove to be the year in which personalized genomic data becomes ubiquitous, who will ultimately assume control of that data?

The answer to that question depends in large part on which party is financing the data generation. Is it a consumer purchasing her whole-genome sequencing from a DTC company? A researcher—whether academic or commercial—enrolling tens or hundreds of thousands of participants into a genomic study? A healthcare provider encouraging preemptive genetic screening?

As genomic sequencing continues to develop into a mainstream activity, 2010 will showcase a variety of pathways through which individuals may receive complete or partial genomic sequences, and ownership and control of that information is unlikely to be uniform, or easily understood. We’ve already examined how genomic information is handled when a DTC company goes bankrupt and under existing Federal privacy regulations, and whether research participants should be granted access to their genomic data.

Today, GINA restricts by law the ability of employers and insurers to access personalized genomic information. But as the amount of available genomic data grows, so too will the possibilities for using (and misusing) that data, and these will not be restricted to employers and insurers.

There is a continuing need for private and public entities to collaborate with individuals in order to clarify how genomic information is owned, stored and accessed across a wide range of possible use cases and to provide individuals and third parties with improved options for data-sharing and data-protection. This dialogue has begun in places, as evidenced by the NIH’s decision last fall to revisit its genomic data-sharing policy, but it remains fragmented. Will 2010 be the year that a leader—or necessity—emerges to broaden and advance the discussion?

Those are some of the top questions on our list as we kick off the new year, and the Genomics Law Report will be closely monitoring how the answers to these questions unfold in the coming months. We invite you to contribute your own questions (and answers, if you’re so inclined) for personal genomics in 2010 in the comments below.