FDA regulation

United States v. Caronia After-The-Fact: What Was All That Fuss About, Again?

April 9, 2013
FDA, Pharmaceuticals

by Ashley Zborowsky, UMN Law Student, MJLST Notes & Comments Editor

In a split decision on December 3, 2012, the Second Circuit issued its long-awaited opinion in U.S. v. Caronia–a case concerning off-label promotion and commercial free speech. The 2011 U.S. Supreme Court holding in Sorrell v. IMS Health acknowledging off-label promotion to be “per se” protected under the First Amendment marked a significant shift in this area of law. Previously, the Food and Drug Administration (FDA) was able to recover billions of dollars in penalties from manufacturers engaged in off-label promotion, or the act of promoting regulated products for uses other than those approved by the agency. Despite other challenges on constitutional grounds, the FDA has been successful at defending its current practice–that is, until recently.

After Sorrell, it was unclear how the Second Circuit would apply this precedent in Caronia. For a robust discussion of the holding in Sorrell and alternate regulatory pathways to mitigate the effects of constitutional challenges to FDA authority, see Rethinking Off-Label Regulation in the Wake of Sorrell v. IMS Health: Can State Involvement Compensate for Waning FDA Authority to Curb Commercial Free Speech? Much to the agency’s chagrin, the Second Circuit found that truthful, non-misleading off-label speech is in fact protected by the First Amendment and therefore cannot be prosecuted under the Federal Food, Drug and Cosmetics Act (FDCA). Although the circuit court opinion is not binding outside of its jurisdiction and is only one early example of how Sorrell will be interpreted by lower courts, the Caronia decision signals potentially diminishing regulatory authority in this realm.

To be sure, the gradual constitutional erosion of its authority to police purported FDCA violations is a viable cause for concern–but is it imminent? Though analysts predicted a more panicked response on behalf of the agency, the FDA has apparently decided not to petition the U.S. Supreme Court for certiorari, stating that the agency “does not believe. . . the Caronia decision will significantly affect [ its] enforcement” of off-label promotion. Because of its limited precedential value and the fact that both Sorrell and Caronia only recognize speech that is truthful and non-misleading as protected, the Second Circuit decision may have very little practical effect. In fact just last month in a related case out of the Ninth Circuit, U.S. v. Harkonen, the court chose to ignore Caronia altogether–asserting that the First Amendment does not protect “fraudulent speech.”

While off-label promotion itself cannot form the basis of an FDCA violation under Caronia, it may still be introduced as evidence of criminal misbranding. As such, it seems that the Caronia uproar could have all been for naught. The FDA’s reaction (or lack thereof) to the Second Circuit’s holding indicates that this is likely true. If nothing else, however, Caronia will surely increase the number of constitutional challenges to FDA enforcement activity, forcing the agency to reexamine its priorities. Thus, while Caronia has the potential for wide-ranging implications down the line, industry stakeholders will just have to wait and see. Although Caronia has done little to alter the regulatory landscape presently, it may only be a matter of time before a circuit split begins to evolve.

United States v. Caronia After-The-Fact: What Was All That Fuss About, Again?

April 9, 2013
FDA, Pharmaceuticals

by Ashley Zborowsky, UMN Law Student, MJLST Notes & Comments Editor

In a split decision on December 3, 2012, the Second Circuit issued its long-awaited opinion in U.S. v. Caronia–a case concerning off-label promotion and commercial free speech. The 2011 U.S. Supreme Court holding in Sorrell v. IMS Health acknowledging off-label promotion to be “per se” protected under the First Amendment marked a significant shift in this area of law. Previously, the Food and Drug Administration (FDA) was able to recover billions of dollars in penalties from manufacturers engaged in off-label promotion, or the act of promoting regulated products for uses other than those approved by the agency. Despite other challenges on constitutional grounds, the FDA has been successful at defending its current practice–that is, until recently.

After Sorrell, it was unclear how the Second Circuit would apply this precedent in Caronia. For a robust discussion of the holding in Sorrell and alternate regulatory pathways to mitigate the effects of constitutional challenges to FDA authority, see Rethinking Off-Label Regulation in the Wake of Sorrell v. IMS Health: Can State Involvement Compensate for Waning FDA Authority to Curb Commercial Free Speech? Much to the agency’s chagrin, the Second Circuit found that truthful, non-misleading off-label speech is in fact protected by the First Amendment and therefore cannot be prosecuted under the Federal Food, Drug and Cosmetics Act (FDCA). Although the circuit court opinion is not binding outside of its jurisdiction and is only one early example of how Sorrell will be interpreted by lower courts, the Caronia decision signals potentially diminishing regulatory authority in this realm.

To be sure, the gradual constitutional erosion of its authority to police purported FDCA violations is a viable cause for concern–but is it imminent? Though analysts predicted a more panicked response on behalf of the agency, the FDA has apparently decided not to petition the U.S. Supreme Court for certiorari, stating that the agency “does not believe. . . the Caronia decision will significantly affect [ its] enforcement” of off-label promotion. Because of its limited precedential value and the fact that both Sorrell and Caronia only recognize speech that is truthful and non-misleading as protected, the Second Circuit decision may have very little practical effect. In fact just last month in a related case out of the Ninth Circuit, U.S. v. Harkonen, the court chose to ignore Caronia altogether–asserting that the First Amendment does not protect “fraudulent speech.”

While off-label promotion itself cannot form the basis of an FDCA violation under Caronia, it may still be introduced as evidence of criminal misbranding. As such, it seems that the Caronia uproar could have all been for naught. The FDA’s reaction (or lack thereof) to the Second Circuit’s holding indicates that this is likely true. If nothing else, however, Caronia will surely increase the number of constitutional challenges to FDA enforcement activity, forcing the agency to reexamine its priorities. Thus, while Caronia has the potential for wide-ranging implications down the line, industry stakeholders will just have to wait and see. Although Caronia has done little to alter the regulatory landscape presently, it may only be a matter of time before a circuit split begins to evolve.

Reviving GRAS(E): Bringing Reform to the Drug Approval Process

April 3, 2013
Food and Agriculture, Healthcare, Healthcare Reform, Pharmaceuticals, Public Health

by Maya Suresh, UMN Law Student, MJLST Staff

Bringing new drugs to the market has turned into a time consuming and costly process. Resulting in a process that takes roughly 12 years and 1.2 billion dollars to develop a single new drug and move it through the approval process, the current laws administered by the FDA have the potential to stifle potential economic growth. Current laws and FDA regulations require new drugs to go through three phases of clinical trials focusing on safety, optimal dosage, and effectiveness. It is in the prolonged third phase (where effectiveness is tested through extensive clinical trials) that many manufacturers decide to pull the drug from the program as the clinical trials threaten the firm’s financial viability. Ultimately, it is consumers that are hurt by the process, as they are unable to benefit from the drugs.

The negative effect on consumers is what Emily Puchalski hopes to eliminate with the recommendation detailed in her note published in Issue 14.1 of the Minnesota Journal of Law, Science & Technology. In “Bringing Dormant GRAS(E) to Bloom: Reviving The GRASE Concept for Drugs,” Puchalski suggests that a revival of the Food and Drug Administration’s (FDA) “generally recognized as safe and effective” laws and regulations, commonly reffered to as “GRASE”, could minimize the negative effects on consumers. Many drugs, once discovered, have formulations found in earlier drugs that have already been established as safe for consumer use. The GRASE law is grounded in this understanding, and provides a way for these “already established as safe” drugs to get to the market quicker without having to go through extensive clinical trials.

The problem with GRASE however, is that it is very difficult for a drug to achieve GRASE status. Due to this difficulty, GRASE has fallen out of use as manufacturers have stopped trying to achieve the status. Puchalski suggests that if the FDA were to revive GRASE, it could convince manufacturers to apply for GRASE status, allowing already established safe and effective drugs to come to market more quickly, thus benefiting consumers.

It would appear that Puchalski’s recommendation is being heard. In late February Micropharma Limited was able to obtain GRASE status for their new heart health probiotic. Ryan Jones, CEO of Micropharma Limited, echoed Puchalski when he spoke of the benefits the company has been able to reap with the highly coveted status. GRASE status will allow the company to accelerate development of the drug within both the United States and international markets. Further, it provides strong reputational benefits for the company, as it makes clear to the public that Micropharma is committed to investing a significant amount of time and energy into providing safe and effective drugs to the market.

The ability for Micropharma to obtain GRASE status could serve as evidence of a potentially reformed drug approval process. However, the full benefits realized by consumers and the market will only become clear with time.

510(k) Process Comes Under Renewed Scrutiny by Legislators, Awaiting FDA Response as Proposed Legislation Remains Stagnant

October 31, 2012
Medical Devices

by Ashley Zborowsky, UMN Law Student, MJLST Notes & Comments Editor

Several months ago, Representative Edward J. Markey (D-Mass.) and Senator Jeff Merkley (D-Ore.) wrote a letter to Jeffrey Shuren, Director of the Center for Devices and Radiological Health (CDRH) at the U.S. Food and Drug Administration, calling for an overhaul of the 510(k) pre-market notification database. The legislators cite reports of defective medical devices cleared via the 510(k) process in recent years, such as the DePuy® artificial hip, that have caused “grievous[] and irrevocabl[e]” harm to patients.

The issue? Most devices subject to premarket review are cleared through FDA’s 510(k) process which provides expedited approval for products that are deemed “substantially equivalent” to an existing predicate device. While the 510(k) process allows patients earlier access to devices, the system is inherently flawed. Referred to as “predicate creep,” the 510(k) process clears generations of devices–none of which have been subject to the exacting scrutiny of pre-market approval (the PMA process). As Markey and Merkley cite in their letter to Shuren, many predicate devices upon which new products rely for 510(k) clearance themselves have been recalled by manufacturers due to “fundamental design flaw[s].”

The legislators asked Shuren and the FDA to retrospectively update the 510(k) database to clearly indicate devices recalled for serious design flaws that could adversely affect safety or effectiveness. The letter also asked FDA, among other things, to develop a mechanism for identifying certain 510(k) entries to “reflect instances where a device’s clearance traces back to a predicate recalled for a serious design flaw adversely impacting its safety, even if the original problematic device is not the immediate predicate.” For additional in-depth discussion of issues surrounding the existing 510(k) process and substantial equivalence, including product liability considerations see “Rethinking Lohr: Does ‘SE’ Mean Safe and Effective, Substantially Equivalent, or Both?”

After the Institute of Medicine released its highly controversial report on the current 510(k) process last year (stating that the process is flawed and recommending a new pre- and post-market regulatory framework to provide a reasonable assurance of safety and efficacy), the issue of device safety has been omnipresent in policy debates surrounding related concerns of access and innovation. For a critique of the IOM report and a summary of its findings, see “A Failure to Comply: An Initial Assessment of Gaps in IM’s Medical Device Study Committee” and “Left to Their Own Devices: IOM’s Medical Device Committee’s Failure to Comply.” In January, Representative Markey and others introduced H.R. 3847, coined The SOUND Devices (Safety of Untested and New Devices) Act of 2012. The bill proposes to amend the Federal Food, Drug and Cosmetic Act to allow the FDA to reject a claim of substantial equivalence for a device whose predicate has been “recalled, corrected or removed from the market because of an intrinsic flaw in technology or design that adversely affects safety . . . .” in light of these concerns.

In testimony given to the House Committee on Energy and Commerce on device user fees back in February, Shuren discussed strategic priorities for the 510(k) process, including developing methods and procedures for the systematic analysis and use of medical device recall information by September 30, 2012. However, now that the Medical Device User Fee Amendments (MDUFA III) have been enacted, reauthorizing device user fees through fiscal year 2017, perhaps the FDA and CRDH will finally be able to make progress in revamping the 510(k) system. As Shuren noted in his testimony, “[w]hile it is true that providing more user fee resources alone won’t solve the problems with our premarket programs, insufficient funding is at the root of, or a contributing factor to, several of these problems. Adequate and stable funding is one key component to our and industry’s success in bringing safe and effective devices to market quickly and efficiently.”

Currently, the 510(k) process remains unchanged. Though legislators requested an official response no later than September 19, 2012, the FDA and Shuren have yet to release a statement (at least publicly) regarding these concerns. Additionally, it is unclear whether CDRH has made any headway in meeting its target goals. As we approach the end of 2012, 510(k) still leaves much to be desired–the highly anticipated changes to the pre-market clearance process are provisional at best. It seems as though Markey isn’t having much luck in Congress either. H.R. 3847 is awaiting approval from the House Committee on Energy and Commerce (and has been since shortly after its introduction). According to GovTrack.us, an online bill tracking website, the bill has only an estimated three percent change of being enacted.

Food Label Regulations Fall Short

October 2, 2012
Food and Agriculture

by Bobbi Leal, UMN Law Student, MJLST Articles Editor

A recent study, published in Agricultural Economics, found that the average body mass index for consumers that read nutrition labels is lower than those that do not read the labels. This finding implies that understanding and utilizing food and nutrition labels provides consumers with the information needed to make informed decisions about what they eat. However, a recent article by J.C. Horvath published in the Minnesota Journal of Law, Science & Technology, “How Can Better Food Labels Contribute to True Choice?” makes evident that food labeling has a long way to go before it truly gives consumers the information necessary to make informed decisions.

Food label regulations, outlined by the Food and Drug Administration, have a number of flaws. The FDA has declined to define strict standards for use of the food label “all-natural,” claiming that the term is too nebulous to be strictly defined and standardized across the entire food industry. Undoubtedly, consumers assume that a food labeled as “all-natural” has not been chemically processed or structurally altered from its natural state. Unfortunately, this is not the case. The FDA has a vague policy which defines the term “natural,” to mean “nothing artificial or synthetic…is included in, or has been added to, the product that would not normally be expected to be there.” According to the Wall Street Journal, some ingredients that have been labeled as “all-natural” include high fructose corn syrup, genetically modified plants, and sodium benzoate.

Similarly, the approved use of certain terms, such as “artificial flavor,” “natural flavor,” and “artificial coloring” often hide significant details about the nature of the food. These three phrases can stand in for over 3900 food additives that come from a wide range of sources, giving the consumer no real notice of the substance or origin of the “flavor” or “coloring.” For example, beef tallow, gelatin, and lard can all be covered by these three phrases. Even the requirements for listing allergens is incomplete, as the FDA only requires that eight of the known allergic-reaction-inducing ingredients be explicitly listed: milk, eggs, fish, Crustacean shellfish, tree nuts, peanuts, wheat, and soybeans.

This recent study concerning the use of nutrition labels makes clear that when consumers read and understand food labels, they can make better choices for their health. In order for this to occur, however, it is imperative that the food labels which consumers rely upon are transparent and accurate. Food label regulations have not yet accomplished this objective.

Contact Information