Government regulation of off-label promotion by pharmaceutical companies is now an important First Amendment issue. The Food and Drug Administration (FDA) has historically restricted truthful and non-misleading speech by pharmaceutical companies under the Food, Drug and Cosmetic Act (FDCA). The FDCA prohibits introducing “misbranded” products into interstate commerce. The FDA has interpreted this to prohibit pharmaceutical companies recommending uses not already approved by the agency (these uses appear in a drug’s labeling). Drugs promoted for unapproved uses may also be considered “new” drugs which require FDA approval. Pharmaceutical companies can also face liability under the False Claims Act for off-label promotion.
United States v. Caronia was the first time the FDCA’s misbranding provisions were successfully challenged under the First Amendment. In 2012, the Second Circuit held that the FDA’s regulations failed the test for commercial speech announced in Central Hudson. Namely, the Court held that restricting truthful speech did not directly advance a government interest (rather, the regulations paternalistically prevented dissemination of truthful information), and the Court held that the FDA’s regulations were more extensive than necessary. The Court did not even analyze the regulations under the test announced in Sorrell v. IMS Health, decided by the Supreme Court in 2011, which held that heightened scrutiny was warranted where restrictions are content- and speaker-based. The FDA did not seek en banc review or writ of certiorari.
Almost immediately, the case was heralded as a landmark decision that would have a profound impact on drug regulation. However, that has yet to occur. Since the case was decided the FDA has already generated large settlements with companies like Amgen for violating agency regulations on off-label promotion. That may be because of uncertainty regarding Caronia’s reach, and because for large companies a relatively cheap settlement makes more sense than risking felony indictments and exclusion from government programs. For the agency’s part, it has tried to avoid fully vetting constitutional issues surrounding its regulations. The FDA stated after Caronia that the ruling would not alter its enforcement policy. Although, the agency has stated it is developing new guidances concerning off-label promotion.
The newest development in this story came last month in Amarin vs. United States. Continue reading →
Here is HHS’s own summary of what has changed and what it thinks is most important:
The U.S. Department of Health and Human Services and fifteen other Federal Departments and Agencies have announced proposed revisions to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects that was promulgated as a Common Rule in 1991. A Notice of Proposed Rulemaking (NPRM) was put on public display on September 2, 2015 by the Office of the Federal Register. The NPRM seeks comment on proposals to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. It is expected that the NPRM will be published in the Federal Register on September 8, 2015. There are plans to release several webinars that will explain the changes proposed in the NPRM, and a town hall meeting is planned to be held in Washington, D.C. in October.Continue reading →
As one of only two countries that permit direct-to-consumer advertising (DTCA) of pharmaceuticals, the United States tasks the Food and Drug Administration (FDA) with regulating that advertising to ensure that it doesn’t mislead consumers. When a drug maker publishes or broadcasts a claim that its drug has benefits in a particular disease, the FDA requires it to include information on the product’s risks as well. Since it’s not feasible for companies to include all the important information about their products in a television ad, the FDA requires them to refer viewers to more complete information, such as that in a printed magazine ad. Companies have tended to comply with this requirement by supplementing colorful, persuasive ads with one or two pages of dry text providing the required disclosures, often simply using language that the FDA has approved for other purposes, such as package inserts for prescribers. But research shows that most patients who attempt to read these disclosures find them difficult to understand, and many don’t even try to make sense of them.1 Now, the FDA is in the process of adjusting its DTCA rules, aiming to provide greater assurance that patients receive due warning of the most significant risks — but its tweaks probably don’t go far enough to really empower consumers to make smart decisions about the drugs they put into their bodies. […]
Are right-to-try laws a good idea? In 2014, they began appearing throughout the United States, first in Colorado and now in 23 states, with several more considering passing versions of this popular legislation.
At first glance these bills may seem worth enacting. Right-to-try (RTT) laws promise terminally ill patients that they can obtain experimental drugs or medical devices in their quests to save or extend their lives. These investigational medical products are still in development and have not yet met the requirements set by the Food and Drug Administration (FDA) in order to be approved for sale or use in the United States. In some cases, the products are still being tested and patient access would primarily be by enrolling in a clinical trial – something terminally ill people may be too unwell to do. Less commonly, the products have completed clinical testing and are waiting for an approval verdict from the FDA. In either case, RTT laws are about providing terminally ill patients access to unapproved drugs or devices. […]
The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School collaborates with Stanford and Duke Universities to publish the Journal of Law and Biosciences (Oxford University Press), an online, open-access, peer-reviewed journal. JLB includes a Notes & Developments section, comprised of brief summaries and commentary on recent legislation, regulation, and case law written by graduate students at the collaborating schools. The PetrieFlom Center is responsible for providing the Notes & Developments for one issue per annual volume.
We are currently seeking Harvard graduate students to contribute papers to be published in JLB’s Notes & Developments section in early 2016. In previous years, Notes & Developments have been generated from scratch specifically for JLB, based on selection from submitted proposals. This year, we are taking a different approach by publishing already complete (or to-be-completed by the deadline) original student papers (such as student notes, course papers, etc.) written by graduate students from any Harvard school. Notes & Developments are limited to 5000 words, including footnotes and references, and should be on a topic of relevance to law and the biosciences, in particular a topic of relatively recent concern, controversy, or change. They should focus on describing the issue at hand, explaining why it is relevant to scholars and practitioners, and providing analysis and questions for further consideration.
Interested students should submit their papers and CVs for consideration no later than September 7, 2015 (earlier is welcome). Up to four papers will be selected for publication in the New Developments section of JLB. Applicants will be notified by the end of September. Selected students will receive comments on their papers by the end of October, and will also be responsible for providing comments to the other selected students. Revisions will be due by the end of November, and final submissions to JLB will be due by the end of December 2015.
Please send all application materials, and direct all questions, to Holly Fernandez Lynch, email@example.com.
What adjective would most people associate with the word “bureaucrat”? For many, it would be “inefficient,” “inept,” or “incompetent.” But another that is just as descriptive is “lifesaving.”
Dr. Frances Kelsey, who died this month at the age of 101, was celebrated as an American hero for her work as a medical officer at the Food and Drug Administration (FDA). She saved thousands of lives and prevented untold suffering by using techniques that earn bureaucrats a bad name, delay and obstruction, to keep the drug thalidomide from reaching the market in the United States in 1961.
Thalidomide is a sedative that had been approved for sale in Europe four years earlier and was prescribed for morning sickness during pregnancy. The American manufacturer, Richardson-Merrell, saw a large potential market in the United States. However, Dr. Kelsey, who was assigned to review its application for marketing approval, was troubled by questionable safety data. The law in effect in 1961 required that she issue a decision within 60 days, but she was able to buy more time by asking for additional information.
Co-blogged with University of Arizona Fellow, Jonathan Loe
Breathlessly, many news outlets reported yesterday that Kim Kardashian West was in trouble with the FDA for misleading social media advertising of the drug Diclegis. For example, the reliably hyperbolic Daily Mail led with “Kim Kardashian slammed by FDA.”
As followers of this blog may not know, Mrs. Kardashian West is pregnant with her second child. Following on the disappointing news that the soon-to-be sibling of baby “North West” will not be named South, the celebrity-for-celebrity’s-sake shared a post on Instagram (and Facebook, and linked to from Twitter, naturally). The post announced for the world that “OMG” her “#morningsickness” had benefited from a prescription of Diclegis—with “no increased risk to the baby.” The FDA issued a warning letter, because the social media post failed to communicate any risk information.
But is the FDA really concerned with people, however famous, commenting on their personal experiences with drugs?
It’s been our great pleasure to collaborate with the Health Affairs Blog on this series stemming from theThird Annual Health Law Year in P/Review symposium at Harvard Law School. This annual event takes a look back over the prior year and previews the year to come with regard to hot topics in health law.
After the symposium, we asked our speakers to keep the conversation going online by expanding on their topics from different angles or by honing in on particularly intriguing features. These pieces were published on the Health Affairs Blog through the spring and into summer.
We heard more from Kevin Outterson on how to promote innovation in the development of new antibiotics, from Rachel Sachs on whether the Food and Drug Administration’s proposal to regulate laboratory-developed tests will really stifle innovation, and from Claire Laporte on the impact of recent Supreme Court decisions on bio-IP.
George Annas weighed in on the Ebola outbreak, which has already almost faded from public consciousness but offers important public health lessons, while Wendy Parmet and Andrew Sussman tackled important developments in tobacco control. […]
[cross-posted at Health Affairs Blog]
On June 16, 2015, the Food and Drug Administration (FDA) released its final determination withdrawing the generally recognized as safe (GRAS) designation for partially hydrogenated oils (PHOs), which are the main source of artificial trans fat in processed foods. The agency gave the food industry three years, until June 18, 2018, to phase out the use of PHOs. The FDA’s order was expected based on the agency’s tentative determination that PHOs were no longer GRAS, published in November 2013.
This action is a milestone in — although perhaps not the culmination of — the FDA’s decades-long attempt to grapple with increasing scientific recognition that trans fat poses a serious health risk to consumers. The action is also unusual, in that it is quite rare for the FDA to withdraw GRAS status from a food product, a move that most likely will mean the ingredient is no longer used in foods.
On May 21, along with my frequent co-author Eli Adashi, I published an op-ed in the New York Timesraising some questions about FDA’s proposed guidance recommending a ban on taking the blood on any man who has had sex with another man in the past year, or in other words imposing a one year celibacy requirement on gay men if they want to donate blood. This built on our critique last July in JAMA, wherein we argued that FDA’s then-lifetime ban on gay men and MSM donating blood was out of step with science and the practice of our peer countries, as well as potentially unconstitutional.
Thanks to our work, and a concerted effort by public health, medical, and gay rights groups, FDA has finally moved off of that prior policy and recognized that it was unjustified, and discriminatory.
Just to put this in context It took more than 30 years to convince FDA that it was problematic to ban blood donation for a lifetime any man who ever had sex with another man, even if both have repeatedly tested negative for HIV, while it imposed only a one year ban on people who had sex with individuals known to be HIV positive or a sex worker. FDA is appropriately a conservative agency, but on this issue of the lifetime ban its willingness to listen and reconsider has gone beyond conservatism to the point of lunacy. [By the way to be clear, I *love* FDA. I represented them while at the DOJ and have a new book coming out about FDA in the fall. You can think highly of an agency but think they have a bad track record on an issue. This is critique not hater-aide].
Well with that background, one should be not so quick to assume that a move to a one year ban — a de facto lifetime ban for any gay man who is sexually active, even one who is monogamously married with children — is the best policy. To put it bluntly, refusing to change a lifetime ban for such a long period makes me skeptical we should accept a “just trust us” line on their new restrictive policy.
The question we raised in our op-ed was whether FDA had adequately justified retaining a one year ban in light of the evidence from places like South Africa (with a much shorter time period ban), Italy (which does individualized risk assessment instead of stigmatizing all gay men as high risk for disease), etc.
A new piece by David Farber, Preeya Noronha Pinto, Bill of Health contributor Arthur Caplan, and Alison Bateman-House the Health Affairs blog:
Over the past year, state Right-to-Try (RTT) laws that claim to enable terminally ill patients to access unapproved, experimental drugs, biologics, and devices have swept the nation. As of early May, seventeen states have enacted RTT laws (most recently, Florida and Minnesota), and bills creating such laws are currently pending in over twenty state legislatures.
Although these laws have created an expectation that terminally ill patients will be able to quickly access potentially life-saving treatments by being exempted from the rules of the U.S. Food and Drug Administration (FDA), this expectation is, quite simply, false.
Last week, the Food and Drug Administration released highly anticipated draft recommendations that would allow gay men to donate blood after one year of celibacy. While an improvement from the current, highly criticized lifetime ban, the new policy, which was announced in December, still caters to fear and stigma rather than science. It should be reconsidered. […]
Earlier today, the House Energy and Commerce Committee released the most recent draft of the 21st Century Cures Act, in time for it to be marked up by the Health Subcommittee tomorrow. At 300 pages, the new draft adds back in a number of provisions that were excised from the previous, 200-page iteration of the draft. I haven’t had time to uncover all of the new additions just yet, but given that this is my third blog post on the subject, I wanted to highlight some of the ways in which this version differs (and doesn’t differ) from the last draft.
Yesterday, a new discussion draft of the 21st Century Cures Act was released, just in time for today’s hearing on the draft before the House Energy and Commerce Committee. At just 200 pages (although with some sections still “to be supplied”), this version is just half the size of the previous draft. As such, it is perhaps more notable for what it took out of the original draft than for what it added in. I haven’t had time to digest fully all of the cuts just yet, but in advance of the hearing this morning I wanted to highlight two significant deletions from the first draft and one potentially significant addition.
First, when I blogged in February about the first draft of the Act, I expressed excitement over the idea of a Medical Product Innovation Advisory Commission. The Commission would have had the ability to oversee the way in which agencies like the NIH, FDA, and CMS all interact with each other to affect the development and dissemination of medical products. A significant portion of my scholarship focuses on precisely these ideas, and I was hopeful that the Commission would make it into the second draft. Alas, it did not.
Second, the first draft of the Act contained a series of very controversial exclusivity provisions. Chief among them may have been the draft provision giving “dormant therapies” (essentially, new drugs for unmet medical needs) the option of 15 years of exclusivity. Alexander Gaffney’s Regulatory Explainer on the first draft provides a helpful overview, for those who are interested in learning more about this provision. But interestingly, this and other provisions relating to increased exclusivity are gone from the new draft. Now, it is possible that some of this language will reappear later, especially as the section of the draft relating to “Repurposing Drugs for Serious and Life-Threatening Diseases and Conditions” has yet to be supplied. But in the first draft of the document, the sections for “Repurposing Drugs” and “Dormant Therapies” were separate, so it is not clear that this is likely to happen.
The Food and Drug Law Journal is pleased to announce a forthcoming symposium—Constitutional Challenges to the Regulation of Food, Drugs, Medical Devices, Cosmetics, and Tobacco Products—to be held at the Georgetown University Law Center (GULC) on Friday, October 30, 2015, and co-sponsored by the Food and Drug Law Institute and GULC’s O’Neill Institute for National and Global Health Law.
Last week, Dr. Salomon Melgen, an ophthalmologist who practices in North Palm Beach, Florida, was indicted on Medicare fraud charges. Melgen was charged with a variety of crimes, with prosecutors alleging he falsely diagnosed patients and falsified their files. Melgen’s name may be familiar. Last year, he was reported to be the provider with the highest total of Medicare Part B reimbursements in 2012, reportedly reimbursed by Medicare for more than $20 million, a substantial percentage of which was directly based upon his prescriptions for, and administration of, the drug Lucentis.
But the allegations against Melgen highlight a deeper challenge facing Medicare.
Harvard Law School
Griswold Hall, Room 110
1525 Massachusetts Ave.
Cambridge, MA [Map]
Please join us for a lecture by Neil Flanzraich, Chairman and CEO of Cantex Pharmaceuticals, Inc., discussing the balance between speed and safety in FDA’s regulation of pharmaceutical products. Topics will include how FDA’s approach has ebbed and flowed over time, the various tools FDA has introduced to reach this balance, and the potential impact of FDA’s various approaches on products and companies, especially start-ups.
Neil Flanzraich graduated from Harvard Law School in 1968 and was appointed by Dean Martha Minow as an Expert in Residence at the Harvard Innovation Lab (i-lab) in fall 2012.
This event is free and open to the public. Lunch will be provided. Full event details are here.
Last fall, the Food and Drug Administration (FDA) finally took steps toward an action that it had been publicly considering for over four years: the regulation of laboratory-developed tests (LDTs). The FDA defines LDTs as tests which are “designed, manufactured, and used within a single laboratory.”
This definition encompasses a wide range of diagnostics, including complex multigene panels that are performed in just a single laboratory in the United States, and basic diagnostic tests like a complete blood count, which are performed in thousands of laboratories nationwide.
As long as a manufacturer does not make and sell a kit for use in other laboratories, its test can be provided as an LDT. Estimates suggest that tens of thousands of diagnostic tests, including the majority of genetic tests, are currently available as LDTs.
Yet at present, the FDA exercises essentially no regulatory authority over LDTs. As such, they can be performed without any of the safeguards that typically apply to other medical technologies, including pre-market review and adverse event reporting. This is not to say that these tests are entirely unregulated. […]
Cambridge, Mass., April 9, 2015 – A paper forthcoming on Friday in Science discusses the regulation of a new technology that gives hope to women who carry genetic disease. Mutant mitochondrial DNA gives rise to a broad range of heritable clinical syndromes. Cure of those affected remains out of reach. However, recently developed Mitrochondrial Replacement Therapy (MRT) – sometimes known as “three-parent IVF” — has raised the prospect of disease-free progeny for women carriers.
In the UK, legislation regulating the clinical application of MRT has recently been approved by the House of Commons and the House of Lords, after a 10-year process.
In the United States, the vetting of MRT, underway for a year, remains a work in progress. A new paper in Science released Friday, April 10, compares and contrasts the regulatory history of MRT in the UK and the United States, discusses the relevant ethical overlay, examines potential lessons learned, and charts the likely path forward in the United States. It is written by I. Glenn Cohen, Harvard Law Professor and Faculty Director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School; Eli Adashi, Professor of Medical Science at Brown University; and Julian Savulescu, Uehiro Chair in Practical Ethics at Oxford University and Director of The Oxford Centre for Neuroethics.
“There is much FDA and the U.S. can learn from the way in which the U.K. has evaluated and regulated MRT,” said Professor Cohen. “These lessons are particularly important because MRT is just one of a series of new reproductive and genetic technologies, including gene editing and In Vitro Gametogenesis, that FDA and regulators across the world will soon be confronting.”