July 24, 2014

Update on State Legislative Efforts to Label Genetically Engineered Food

An update on the efforts to enact state laws that mandate the labeling of genetically engineered (GE) foods: at present, Connecticut and Maine have enacted conditional GE food labeling laws, which are not to take effect until a requisite number of neighboring states also pass such laws; effectively, these laws are dormant right now.  In contrast, Vermont passed a GE food labeling law, Act 120, in April of this year, with its mandates to take effect in July, 2016.  Vermont did not follow the conditional model set by the other states, and supporters of the law expected litigation to follow. Since the enactment of this law, Vermont has been sued by the Grocery Manufacturer’s Association and other trade groups, which filed their complaint in June. The complaint alleges a violation of the First Amendment, arguing that the manufacturers will be subject to a form of compelled speech, and as such, this amounts to an impermissible content-based regulation that is unconstitutional. Even accounting for the sometimes more deferential review of speech-related laws that target commercial entities (see 1980 Central Hudson v Public Service Commission), the plaintiffs assert that the state even fails to muster a “substantial government interest,” noting the failure of an earlier Vermont labeling law on dairy products produced from BGH-few animals to pass constitutional scrutiny in International Dairy Foods Association v. Amestoy (2nd. Cir. 1996) (one of the plaintiffs in this current litigation, the International Dairy Foods Association, had challenged the earlier law as well). The complaint against the Vermont GE law further alleges a Fifth Amendment defect pertaining to the vagueness of some terms in the statute, as well as a dormant Commerce Clause violation in view of the extraterritorial effects of the Vermont law on companies based outside Vermont who would be required to “establish Vermont-specific distribution channels.” As this litigation unfolds, efforts continue to mandate GE food labeling in other states. Active legislative efforts are underway in Pennsylvania, New Jersey, Illinois, Massachusetts and New Hampshire. Lastly, voter-initiated ballot measures to mandate GE food labeling will appear this fall in Colorado and Oregon (earlier initiatives in Washington (2013) and California (2012) failed by narrow margins).  All of these state efforts arise in the absence of (and official resistance to) any federal scheme for mandatory labeling of GE foods; the FDA imposes no such requirement but does allow voluntary labeling.

July 20, 2014

Cambridge Working Group: Scientists Call For Limiting Experiments on Potentially Pandemic Pathogens

A new coalition of scientists, the Cambridge Working Group (CWG), has emerged with the goal of entering into the debate over whether and how scientific experiments that deliberately create new pathogens should be conducted. This class of experiments aims to understand how mutations introduced into the genome of a known pathogen (e.g., H5N1 influenza virus) alter its properties. One of the goals cited for these experiments is to assist public health officials in identifying the emergence of potentially worrisome (viral) strains, with possibly pandemic potential. However, concerns over the safety of these laboratory experiments have been heightened in view of recent high-profile biosafety lapses in government labs (see here). Some of the scientists in the CWG have been members of the National Science Advisory Board on Biosecurity (NSABB), the federal advisory group that advises on biosecurity issues and dual-use research (NSABB has just announced a reshuffling of personnel, replacing almost half the current roster with new members). The controversy of two years ago, where “gain-of-function” (GOF) experiments with H5N1 influenza virus were conducted and then published has continued as new experiments with what have been called “potential pandemic pathogens (PPP)” continued. The class of PPP could constitute de novo constructed viruses or could also include attempts to recreate previously known and dangerous pathogens. Recently, one of the same labs that had published the H5N1 influenza experiments in 2012 reported that it had created a new influenza virus homologous (similar) to the 1918 influenza virus, which caused a pandemic that killed between 20-50 million people (the CDC had already reconstructed the 1918 virus in 2005). This week, the CWG announced its formation and issued this statement:
Recent incidents involving smallpox, anthrax and bird flu in some of the top US laboratories remind us of the fallibility of even the most secure laboratories, reinforcing the urgent need for a thorough reassessment of biosafety. Such incidents have been accelerating and have been occurring on average over twice a week with regulated pathogens in academic and government labs across the country. An accidental infection with any pathogen is concerning. But accident risks with newly created “potential pandemic pathogens” raise grave new concerns. Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control. Historically, new strains of influenza, once they establish transmission in the human population, have infected a quarter or more of the world’s population within two years. 

For any experiment, the expected net benefits should outweigh the risks. Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches. A modern version of the Asilomar process, which engaged scientists in proposing rules to manage research on recombinant DNA, could be a starting point to identify the best approaches to achieve the global public health goals of defeating pandemic disease and assuring the highest level of safety. Whenever possible, safer approaches should be pursued in preference to any approach that risks an accidental pandemic. 
The field of molecular biology previously confronted a scenario where the development of new technologies outpaced a thorough assessment of their potential risks. In a 1974 statement from a committee of the National Academy of Sciences that considered then-emerging recombinant DNA experiments, the concerns expressed about that technology are similar to the current responses to PPP experiments, although today’s concerns apply to the possible enhancement of already known pathogens. That 1974 report stated:
Several groups of scientists are now planning to use this technology to create recombinant DNAs from a variety of other viral, animal, and bacterial sources. Although such experiments are likely to facilitate the solution of important theoretical and practical biological problems, they would also result in the creation of novel types of infectious DNA elements whose biological properties cannot be completely predicted in advance. 
The new CWG call for an Asilomar-type approach to evaluating and managing the risks of PPP experiments references the foundational 1975 Asilomar conference called by scientists to deliberate how recombinant DNA experiments could be safety performed. That conference established principles for conducting the new recombinant DNA experiments, leading to the issuance of the 1976 Guidelines by the newly formed Recombinant DNA Advisory Committee (RAC) (see recent post on RAC’s future). It is important to note that there is disagreement within the scientific community regarding the need for GOF influenza (PPP) experiments; see here for a brief on the value of such work and here for a critical take on such research. The call for further investigation of PPP research by the scientific community echoes the approach of Asilomar, but it also serves as a notice to regulatory authorities (e.g., funding agencies) that the scientific community is aware of public concerns and is responding with deliberation. Professional self-regulation could preempt government-initiated controls on PPP research, such as funding restrictions.

July 17, 2014

Biosafety Lapses With Anthrax, Smallpox and Influenza Pathogens in Government Laboratories: Federal Oversight Revisited

Recent developments regarding the biosafety practices in several government laboratories have raised concerns about the containment of potentially dangerous pathogens in scientific research. In the past month, a series of separate incidents exposed weaknesses in the oversight and management of dangerous pathogens. These included the accidental exposure of CDC scientists to anthrax in CDC labs, the discovery of forgotten vials of viable smallpox virus in an FDA lab housed at the NIH, and an unintentional cross-contamination of a benign influenza strain with a dangerous H5N1 influenza and its subsequent transfer. All of these events involve naturally occurring pathogens, but these events also occur at a time when public debate continues over the deliberate creation of potentially dangerous pathogens in the field of dual-use research of concern (DURC). With scientists reporting the creation of new pathogens in order to define what genetic changes correlate with pathogenicity or transmissibility, concerns emerged as to how such scientific detail should be publicly shared, and how such pathogens were to be safely contained in the laboratory environment. Most of the attention focused on the publication of genetic detail, evidencing concerns that the pathogens could be reconstructed for malicious intent. However, an equally serious concern related to the possibility that the newly designed pathogens could be released inadvertently, due to laboratory or personnel errors. This recent series of safety lapses now amplify the concerns over the general state of biosafety practices in laboratories handling the most dangerous pathogens, whether natural or engineered. Although the standards for the containment of dangerous pathogens in laboratories are well-known and generally followed, one untoward release of a high-risk infectious agent could be catastrophic. In general, there are established biosafety protocols which define the type of required facilities, procedures and personnel based on the level of risk that a particular pathogen poses to public health and/or the environment. The guidelines assign a biosafety level (BSL) based on that analysis; the high-containment BSL-3 and BSL-4 labs are required for work with the most dangerous pathogens. In addition, the transport of such pathogens is also managed with protocols that establish safe transfer. The CDC director, Dr. Thomas Frieden, conceded the pattern of biosafety lapses in a press conference and at a Congressional hearing yesterday. Dr. Frieden has shut down several labs and instituted a moratorium on some shipments of pathogens. The Government Accountability Office (GAO) has conducted several studies on laboratory safety in high-containment laboratories (private or public), specifically noting the absence of any overarching federal body to oversee these laboratories, particularly in view of their proliferation in the years since 9/11 (the anthrax incidents), as bioterror-related research has increased (note recent controversy over a BSL-4 lab established in Boston). The GAO was represented at yesterday’s hearing, and it reminded Congress of their previous investigations and recommendations on laboratory safety; the recent incidents may cause Congress to revisit this work and act accordingly.

June 30, 2014

PTO Reacts to Supreme Court Cases on Patentable Subject Matter in Biotechnology and Software

New developments in the question of what subject matter is eligible for patenting illustrate how this seemingly foundational question for the high-tech fields of biotechnology and software remains unsettled, even decades after these industries entered the commercial sector. Patenting for these technologies must not run afoul of the long-standing prohibition on patenting natural phenoma, laws of nature and abstract ideas. Recent years have seen the landmark cases of AMP v. Myriad (2013) and Mayo v. Prometheus (2012) issue from the Supreme Court and impact the life science sector. Myriad took on the eligibility of product claims that derived from natural substances or chemicals (e.g., genes/isolated DNA) and found them invalid. Mayo considered the eligibility of method claims where a natural correlation or relationship was embedded in the claim, therefore risking the possibility that the patent claim “preempts” the use of the natural correlation, and invalidated a method claim for optimizing drug dosage because it violated the prohibition on patenting laws of nature. Following these cases, the U.S. Patent and Trademark Office (PTO) issued new subject matter guidance for patent examiners in applying these holdings to the examination of new patent applications. This guidance document was discussed in an open forum in May of this year, and the PTO has extended the deadline for public comments to July 31, 2014.  Last week, at the annual BIO convention in San Diego, the PTO presented a set of model patent claims derived from the discovery of a protein antibiotic and written post-Myriad, and invited further comments. So the question of how life science patenting steers clear of capturing natural, uninvented subject matter continues. In the field of software patenting, a different question continues to be debated. The patenting of computer-based  technologies, which allow all manner of operations and processes to be carried out through digitization/computer code, must not cross over into the patenting of abstract ideas. Until this month, the most recent precedent on this point, Bilski v Kappos (2010), disallowed the patenting of a computer-implemented scheme for hedging against the risk of price changes because the Court declared that it was no more than an abstract idea. Just two weeks ago, the Supreme Court issued Alice Corporation Pty. Ltd. v. CLS Bank International, in which patent claims to a computer-implemented scheme for mitigating settlement risk in transactions. The Court declared the patent claims also invalid as they improperly claimed an abstract idea, which is not patentable. The PTO has issued new preliminary examination instructions that apply Alice Corp. to patent examination practice. Both lines of cases (life science and computer-related) reiterate existing precepts of patentable subject matter, but the interpretation of these cases remains unsettled. With the comment process now underway at the PTO on the post-Myriad/Mayo guidelines that extend the logic of the ruling on isolated genes to many other natural substances and products will be revisited, but it's possible that full development of the scope of this exception will again require judicial review.

June 29, 2014

FDA and 23andMe Restart the Regulatory Process for Oversight of Genetic Testing Services

The need for regulation of genetic testing offered by genomics companies has been debated for years, accompanied by mixed signals from the FDA over its role in such efforts. The bulk of genetic testing services offered by private companies are offered as laboratory-derived tests (LDTs) that are purchased from the test developer. Laboratories providing LDTs are regulated under the Clinical Laboratory Improvement Amendments (CLIA), administered by the Centers for Medicare and Medicaid Services (CMS), which requires that laboratories meet specified standards, and that individual tests are scientifically accurate, but which does not evaluate the clinical validity or clinical utility of LDTs. In addition, direct to consumer (DTC) genetic tests are offered directly to the public and do not require a medical intermediary; results are provided to the client. The industry has long argued that its services were simply LDTs that did not require formal review as medical devices, but simply had to meet the general CLIA standards for clinical laboratories. However, the FDA has recognized that genetic testing may pose special concerns that warrant specific attention and reacted accordingly. In 2010, the FDA sent warning letters to a number of genetic testing companies, including 23andMe, advising them that their genetic services, although direct to consumer, met the classification of a device that required FDA approval as medical devices. A Government Accountability Office (GAO) investigation in 2010 found that several companies provided inconsistent results to undercover consumers, and that the information provided also did not line up with the consumer’s actual clinical status. The Federal Trade Commission, publishes consumer alerts stating that DTC genetic tests may not be reliable and warning that consumers may be deceived by marketing claims. 

23andMe has offered several kinds of genetic testing, ranging from tests assessing risk for an individual disease or condition to aggregate testing for hundreds of DNA variants across an individual’s genome. A consumer receives information regarding possibly significant DNA variants identified in her genome, as well as a health report from the company assessing medical risk based on the genetic data. The FDA was most concerned about the company health report because it could form the basis for consumer medical decision-making using possibly weak or non-credible information. In 2012, 23andMe announced that it had filed a premarket notification submission to the FDA for its $99.00 Saliva Collection Kit and Personal Genome Service (PGS), a service offered since 2008. However, the company did not properly respond to the FDA’s inquiries and comments in the period that followed. As a result, in November 2013, the FDA ordered 23andMe to cease offering the (PGS) test product; the company complied and announced that its health reports would be discontinued (only providing "uninterpreted raw genetic data"). Now, the company has announced the filing of a premarket submission for a genetic test for Bloom’s syndrome – indicating a restart to its regulatory path with the FDA and even optimism: 
Once cleared, it will help 23andMe, and the FDA, establish the parameters for future submissions. More importantly, for our customers, it marks a baseline on the accuracy and validity of the information we report back to them. The submission includes robust validation data covering major components of our product such as the genotyping chip, software and saliva kit. 
As the contours of the regulatory process traveled by 23andMe for its services becomes clear, other personal genetic testing companies are likely to follow suit and the FDA could begin to offer an orderly oversight structure for the products and services offered by this industry. Given the status of 23andMe as a flagship genomics company, and the hesitant moves by the FDA over these several years, the outcome of this submission and review will sketch out a regulatory path for the industry. However, reaction to FDA involvement is mixed; critics contest the level of consumer harm created by these products and argue that consumers should have the right to obtain their genetic data without government interference, noting the First Amendment right to receive information. Future consumers might contest excessive regulation on that basis.