Genetic Labeling: Legal Uncertainty for Pharma Product Liability

Customization of products and services is becoming increasingly popular. Today, we can individualize anything from a salad to a car. In fact, surveys from Bain & Co. and Deloitte have confirmed that over one-third of consumers are interested in personalized products.

Advances in health care are making it more customized as well. Former President Barack Obama brought the discussion to center stage when he announced the Precision Medicine Initiative in his State of the Union Address in January 2015. Precision medicine challenges the idea of “one-size-fits-all” health care and considers individual variations in environmental, lifestyle, and genetic factors when developing and administering
treatment.

In the last 10 years, advances in technology have made precision medicine both scientifically and economically feasible. In 2003, when the concept of precision medicine was first addressed in mainstream health care, it cost $2.7 billion to sequence a human genome. Today, it costs only $2,900. Additionally, tests that measure gene expression, such as Northern and Western blots, have increased in accuracy and cost-effectiveness. These developments are key to finding more targeted treatments for cancer and rare diseases. Moreover, the explosion in affordable direct-to-consumer genetic testing (through companies like 23andMe) means that more personal information is in the hands of patients and their physicians.

Direct-to-Consumer Genetic Tests

The FDA's recent approval of 23andMe's direct-to-consumer genetic test to identify genes associated with 10 common diseases and disorders could result in a widespread expansion of patients armed with individualized health information. Consumers can purchase the test for only $199, submit a sample of their DNA, and receive the result — all without visiting a physician. This expansion of genetic information in the hands of consumers potentially impacts regulatory and litigation issues for pharmaceutical companies.

A byproduct of the availability of genetic information raises questions for the health care industry about the role of this information in treatment and prescription drug design. This article explores the potential legal issues specific to pharmaceutical products liability arising from increased access to genetic information. Heightened consumer awareness of genetic makeup could modify failure to warn claims, change expert testimony, and blur the lines between pharmaceutical manufacturer and medical practice.

Failure-to-Warn Claims

Typically, plaintiffs include failure-to-warn claims in prescription drug product liability suits. A drug manufacturer can be liable for inadequately warning about adverse events if the manufacturer knew of a risk but failed to warn prescribing physicians, and that failure to warn, and the plaintiff's use of the drug, proximately caused a plaintiff's injuries.

The increased accessibility to genetic information could encourage plaintiffs' counsel to modify traditional failure-to-warn claims by including additional allegations that the manufacturer failed to warn about adverse events associated with specific genetic mutations. Plaintiffs have already started testing this theory of liability. In a 2011 case, Mills v. Bristol-Myers Squibb, 2011 U.S. Dist. LEXIS 116701 D. Ariz. 2011), the plaintiff argued the manufacturer should have warned that Plavix was not as effective for people with a certain gene called “CYP.” The plaintiff had no evidence, however, that she actually carried the CYP gene, due to the expense of genetic testing. The court dismissed her failure-to-warn claim because she had no evidence that suggested a warning would have prevented her injury.

However, had the plaintiff proven that he had the CYP allele (something that is becoming progressively easier due to the expansion of consumer-driven genetic testing), this could have been compelling evidence for causation, and could provide a convincing argument that the warning's inadequacy proximately caused injury. Thus, technology that allows individuals to more easily obtain their genetic information, such as 23andMe, could provide game-changing evidence for plaintiffs to assert innovative failure-to-warn claims.

Currently, the Food and Drug Administration (FDA), the oversight body for labels accompanying prescription drugs, does not require a section in the label warning about genetic interactions with the medication. However, in January 2013, the FDA issued guidance instructing manufacturers to include genetic information in the label “only if it is useful to inform prescribers about the impact (or lack of impact) on a genotype.” FDA, U.S. Dep't of Health & Human Servs., Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling 19 (2013). While this FDA guidance is non-binding, the language could provide a hook for plaintiffs' counsel to argue in failure-to-warm cases that manufacturers are in the best position to warn prescribers and patients about adverse events associated with particular genetic mutations.

Expert Testimony

In order to establish that a prescription drug caused their injuries, plaintiffs often use expert testimony. The ability to confirm that a plaintiff has a particular genetic mutation could open the door for expert discovery into the genetic mutation's interaction with the medication.

So far, there are no known cases where such testimony has been allowed, but it likely is coming. Some experts have unsuccessfully attempted to testify that the plaintiff had a genetic mutation known to interact with or decrease the efficacy of a medication. In Agee v. Purdue Pharmaceuticals, No. CIV-03-0787-HE (W.D. Okla. 2004), aff'd, 242 F. App'x 512 (10th Cir. 2007), when the expert tried to testify the plaintiff was a “slow metabolizer” of the medication, and this slow metabolism led to an overdose, the court refused to allow the testimony because the expert “did not have any basis for concluding that [plaintiff] was a 'slow metabolizer.'” However, if the plaintiff in that case had been able to demonstrate the existence of a genetic mutation linked to slow metabolism, the court might have been more willing to allow that plaintiff's experts to testify about the implications of the genetic mutation, provided there was adequate evidence to establish the interaction between the medication and the genetic mutation.

Additionally, it is not clear whether courts would consider results from 23andMe or other over-the-counter genetic tests, alone, to constitute sufficient evidence that an individual has a gene, for expert testimony and causation purposes, without also having the gene confirmed under the supervision of a medical provider or genetic counselor. In the end, the availability of genetic testing could increase the costs of defending lawsuits, because even where such expert testimony is not ultimately permitted, the parties to the case have to brief the issue.

Communicating Genetic Consequences to Physicians

If more pharmaceutical manufacturers volunteer or are required to include genetic information in the label, it is unclear how much and what type of information is necessary to be considered helpful to prescribers.

When warning about genetic interactions with medication, or even the potential for a genetic effect on dosage, pharmaceutical manufacturers must be cautious not to overstep their bounds and intrude on the practice of medicine. However, many prescribers are not well-versed in genetics, and warnings about the presence of a particular gene increasing adverse-event risk may complicate the practice of medicine. Gene expression is a complicated process dependent on a variety of factors, including interactions with other genes. Individuals can have a gene, but not express it at all, or only partially express the gene. The same gene can have a different result in two different people. Thus, just because an individual has a particular gene does not mean she will actually express that gene in a way that produces the adverse event.

Finally, it is unclear how physicians will handle patient discussions regarding 23andMe results and how pharmaceutical labels will inform those discussions, if at all, without interfering in the practice of medicine. Ultimately, then, availability of patients' genetic information will likely make physician decisions more complicated.

While the physician will have access to a patient's information, it still may be confusing for the physician to weigh the costs and benefits of performing tests to determine if the individual has the gene or if the gene is expressed. If pharmaceutical manufacturers include too much information about genetic mutations in the label, it could overwhelm busy physicians and cause them to discount the genetic mutation section altogether. Conversely, merely mentioning that a genetic mutation could result in an interaction does not provide a physician with adequate information to determine whether a test for the mutation is warranted.

Conclusion

The legal implications created by easier access to genetic information as a byproduct of precision medicine are vast, but uncertain. Now that consumers can identify whether they have certain genetic mutations through 23andMe, or one of its inevitable competitors, should pharmaceutical manufacturers examine the effects of these genes on the medication in clinical trials so they can warn about any potential adverse events? Should manufacturers change the inclusion criteria for clinical trials to include individuals with these genetic mutations?

As technology advances, additional regulations on genetic labeling are needed from the FDA as the law struggles to catch up with new advancements.

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Shannon E. McClure is a partner in Reed Smith's complex litigation group in the Philadelphia office. Whitney Mayer is an associate at the firm. This article also appeared in the Pennsylvania Law Weekly, an ALM sibling publication of this newsletter.