July 31, 2011
Genetic tests fall into the category of medical devices for the purpose of identifying regulatory requirements administered by the Food and Drug Admistration (FDA). As most commercially available genetic tests are offered as laboratory developes tests (LDT), not retail products, they are largely unregulated by the FDA (save for the separate general oversight of U.S. laboratories under the Clinical Laboratory Improvements Amendments, known as CLIA). However, the FDA has stepped into some regulation of genetic tests; for example, recommending that developers of pharmacogenomic tests consult with the agency before deciding whether to submit a premarket notification submission -510(k) - or the more demanding premarket approval application. This sporadic regulation of genetic tests has occurred against a backdrop of perceived deficiencies in the overall regulation of medical devices - most notably, criticism that too many moderate-risk medical device suppliers are allowed to simply notify the FDA of a new device entering the market, rather than request approval of such action. Further elaboration is available in this summary document from the Government Accountability Office. This week's report of a lengthy study on the 510(k) device clearance process by the Institute of Medicine (IOM) calls for largely scrapping the premarket notification program as it exists in favor of stricter pre- and post- approval mechanisms. The upshot for genetic testing regulation is that more sophisticated classification of genetic tests will likely result in risk sorting that will adjust regulatory demands, and if the FDA begins to tighten the medical device entry process across risk categories, genetic tests are likely to be swept along. The College of American Pathologists, which has called for risk classification and increased regulation of LDTs, notes that the new IOM proposals overlap with their own calls for LDT regulation.
July 30, 2011
The long-awaited Federal Ciruit decision on the patent eligibility challenge from assorted plaintiffs (patients, physicians, medical organizations) to the BRCA1 and BRCA2 patents has issued. In 2010, the lower federal court in New York had declared that genes are not patentalbe subject matter, relying on product and law of nature doctrines for its ruling. Now, the appellate court has rejected that conclusion, reasoning that the isolated DNA claimed in the patents has a "distinctive chemical identity" that is different from the native DNA, thus reflecting an inventive intervention which allows the compositions to be patentable subject matter. My own view of the eligibility question relies on an examination of the gene as a molecule with a bifurcated legal identity that complicates its patent eligibility; I conclude that the patent of genes results in effective preemption of the genetic code, thus violating the prohibition on patenting laws of nature. For more exposition of this argument, my amicus brief is available: Kane Amicus Brief AMP v USPTO 2010. The Court did further decide that the method claims in the case were ineligible; more analysis will be forthcoming of the method claims.
July 27, 2011
The ongoing debate over the limits of government collection of DNA samples for inclusion in national DNA databases, most notably the CODIS database, has recently focused on whether those arrested for a crime can be ordered to submit a DNA sample for inclusion. In a decision from the 3rd Circuit Court of Appeals in Philadelphia, the court upheld the constitutionality of the Kyl amendment to the Violence Against Women Act in 2006, which authorized the federal government to collect a DNA sample from those arrested of a federal crime. The inclusion of arrestees as subject for inclusion in state DNA databases has increased with more states expanding their authorizing legislation; for a comparison of state laws, see here.
Labels: DNA Evidence
July 24, 2011
The field of pharmacogenomics, in which pharmaceutical treatments are informed by genetic analysis, allows for more individualized therapeutic regimens. This field is also described as personalized medicine. The Public Library of Science hosts an online repository, Evidence on Genomic Tests, that publishes peer-reviewed reports of genomic tests used in clinical practice. These are short, summary reports, which, interestingly, attend to the key attributes that need to be studied in genetic testing: analytic validity, clinical validity, and clinical utility. For more information on these parameters, see the 2008 Report by the HHS Advisory Committee on Genetics, Health and Society on the U.S. oversight of genetic tests. One such report recently studied the Oncotype DX, which is a genetic test that aims to predict the possibility of recurrence for breast cancer patients by analyzing the variations in a discrete 21-gene set which correlate to either lower or higher recurrence risk. The clinical import is that women with lower risks of recurrence, as identified by Oncoptype DX, could receive less aggressive followup treatment, such as adjuvant chemotherapy. The report concluded that, as yet, there is some analytic validity, some clinical validity, but concluded: "There is currently no data clearly demonstrating clinical utility of Oncotype DX in women with lymph node-positive breast cancer." While these phamacogenomic tests have received critical attention, leading to some FDA oversight, it is important to simultaneously monitor how these tests are actually faring in practice. This is key for patients who could be spared unnecessary treatment, but also for patients who might unduly be denied treatment, either conclusions might be drawn from these tests. In addition to frank medical concerns, insurance coverage for these tests varies and presents additional complications. This report reminds us that, as the debates over a proper regulatory framework for genetic testing continue, the scientific evaluation of proposed pharmagenomic modalities is relatively recent, currently ongoing, and far from completed.
July 20, 2011
The use of genetically engineered plants or animals as factories for the production of desired proteins is a strategy with a relatilvely long shelf life in modern biotechnology. It's fair to say that the prospect of taking genes that encode therapeutically desirable proteins and putting them into bacteria, animals or plants for low-cost, high-output production was one of the first commercial applications of biotechnology that attracted investment. Clinical testing of these products continues to expand. "Pharming" is the term that has been applied to the use of plants or animals to generate new proteins from introdouced DNA. In 2009, the FDA issued the first approval for a drug produced from genetically engineered animals – the anticoagulaten Atryn produced in the milk of goats. The FDA has also approved the study of a tumor vaccine derived from genetically-manipulated (not engineered) tobacco plants, and clinical trials began in 2010. Now the UK has approved a clinical trial testing the use of an anti-HIV microbicide (a monoclonal antibody) for women that is produced from tobacco plants. This will be the first clinical trial in Europe for a therapeutic derived from genetically engineered plants.
July 16, 2011
We are seeing the era of full clinical evaluation of stem cell therapies unfold. This week brings an announcement by Advanced Cell Technology in California that the FDA has approved two more clinical trials using human embryonic stem cells (hESC) for retinal transplantation in patients with severe opthamalogic disease. In the laboratory, the stem cells were differentiated into retinal cells. The cells are transplanted, and these initial infusions will asses safety and tolerability of the cells in these individuals. The first FDA-approved clinical trial of hESC was announced last fall by Geron in which the stem cells were differentiated into neuronal cells and transplanted into patients with spinal cord injury, in an attempt to restore motor activity and induce nerve repair. The clinical trials began with the FDA approval of the Geron trial in January, 2009, just after the start of the Obama administration, which had vowed to lift the Bush-era restrictions on research into hESC. An Executive Order was issued in March, 2009, which did exactly that, unambiguously:
For the past 8 years, the authority of the Department of Health and Human Services, including the National Institutes of Health (NIH), to fund and conduct human embryonic stem cell research has been limited by Presidential actions. The purpose of this order is to remove these limitations on scientific inquiry, to expand NIH support for the exploration of human stem cell research, and in so doing to enhance the contribution of America’s scientists to important new discoveries and new therapies for the benefit of humankind.The full determination of the clinical promise of hESC therapies (or those derived from adult stem cells) will take years. But the field certainly cannot contend with an erratic regulatory climate and unsettled expectations, which is what has happened for nearly a decade.
July 14, 2011
The international organization UNITAID lanched an initiative, the Medicines Patent Pool, as an effort to bringing lower cost drugs ro those in developing countries who cannot afford such treatments – and where patent rights held by global pharmaceutical companies frustrated the development of lower cost alternatives in these countries. The pool invites patent holders to submit their patent rights for inclusion, thus agreeing to an affordable licensing model for genetic companies around the world. From the mission statement:
The Pool is a win-win-win model, whereby patent holders are compensated for sharing their patents, generic manufacturers gain access to markets, and patients benefit more swiftly from appropriate and adapted medicines at more affordable prices.To date, the pool’s largest obstacle is to induce the holders of patents to successful drugs to submit their patent rights, knowing that the licensing of the same is unlikely to generate any significant revenues. NIH licensed its patent to darunavir, an anti-GIV drug, last year. Now comes word that Gilead Sciences, Inc. has submitted 4 patents on AIDS drugs to the pool, vastly incnreaing its anti-HIV portfolio. A great step forward for the concept of an equitable patent pool, but more importantly, for the patients currently underserved by the pharmaceutical marketplace. What a radical shift from the days when a phalanx of pharmaceutical companies took South Africa to court when it attempted to legislate the use of parallel imports of patented drugs and allow compulsory licensing in 1998 in order to ease the effect of high prices on AIDS drugs. The lawsuit was later dropped, but the legislation was also eased, and the government ultimately negotiated with the drug companies for lower prices in order to increase access. The entry by Gilead into the patent pool bodes well for the use of this mechanism as a tool to fight AIDS, but other diseases as well. UNITAID is also targeting malaria and tuberculosis.
July 9, 2011
One of the most common assisted reproductive technologies (ART) involves in vitro fertilization, followed by implantation and birth. The use of IVF is often sought by couples at risk for transmitting genetic disease, and a technique known as preimplantation genetic diagnosis (PGD) allows fertilized embryos to be tested prior to implantation with the goal of only implanting those free of the genetic condition. This technique is routinely used in the U.S. and most of Europe; here is the standard PGD recommendations issued by the American Society for Reproductive Medicine (ASRM). Against the backdrop of the German Embryo Protection Act, which has been interpreted to prohibit PGD use, the German parliament has voted to remove the prohibition against the use of PGD, thus bringing Germany in line with the rest of Europe. What was notable about the holdout over PGD in Germany was that methods for prenatal diagnosis (PND) during pregnancy are widely used, with the possibility that abortion remains an option to avoid the birth of a child with genetic disease. With that option already available, the absence of the preventive measures offered by PGD were increasingly viewed as contradictory, not to mention out of step with the ART options available in most Western countries.
Labels: Reproductive Technologies