Biotechnology

Your Property Nightmare Just Got Worse: Assisted Reproductive Technology and the Rule Against Perpetuities

August 7, 2025
Biotechnology, Property Law, Public Health, Reproductive Health

Peyton Soethout, MJLST Web Content Editor

The Rule Against Perpetuities (“Rule”) has been drilled into law students’ brains for decades; “no interest is good unless it must vest, if at all, not later than twenty-one years after some life in being at the creation of the interest.”[1] The Rule can be tough to grasp, so think of this common example: “T leaves Blackacre ‘to my grandchildren who shall reach the age of [twenty-one].’”[2] Under the common law Rule and in general circumstances, this gift is valid.[3] That is, assume T and T’s children all die. But, on T’s child’s last day on Earth, they gave birth to T’s grandchild. That grandchild would turn twenty-one and gain the interest within the Rule’s permissible timeframe. This used to be a simple example of the Rule. However, as assisted reproductive technologies (“ARTs”) continue to develop, the example presents a slew of unanswered questions.

Multiple technologies fall under the umbrella of ARTs, but cryopreservation of reproductive genetic material and in vitro fertilization (“IVF”) are some of the most common. Many ARTs were first successful during the late 1970s and early 1980s.[4] From then on, it became possible for T’s grandchildren to be born multiple years after T’s and T’s children’s deaths. That is, sperm, ovum, and embryo could be cryopreserved—or frozen—after the deaths of the individuals that genetic material was taken from.[5]

Shortly after the initial success of ARTs, legal scholarship attempted to address ARTs’ effect on the Rule.[6] Some scholarship suggests the Rule should follow Barton Leach’s proposal that the Rule should focus on the concept of paternal rights and “that the duration of a male life in being under the Rule should ‘be defined as the period of his reproductive capacity, including any post-mortem period during which his sperm remains fertile.’”[7] Others suggest an outright exclusion of cryopreserved matter when making Rule determinations.[8] Finally, some suggest “a rebuttable presumption that the will contains an implicit provision stating that ‘nothing in this will shall be construed to provide an inheritance for any posthumously born individuals.’”[9] Despite a variety of proposed solutions, it is unclear if any proposal was successful in any jurisdiction.

The lack of clear guidance on the relationship between ARTs and the Rule is especially concerning as the most recent article on the topic was published in 2008.[10] At that point, “[c]ryopreservation of mature, unfertilized eggs [was] not standard clinical practice.”[11] Additionally, the length of time a frozen sperm could remain viable after collection was unknown.[12] In the last two decades, however, the likelihood of fertility technology success and the length of time the cryopreserved matter is viable has grown drastically. Recently, cryopreservation of eggs “went from an experimental procedure to a promising insurance policy.”[13] Cryopreservation of ovarian tissue has only been available for about twenty years and has only been likely successful in the last ten years.[14] With the general rise in ART success, over a hundred countries practice ART.[15]

The likelihood of success of ARTs is especially important when considering the Rule as it relies on the rule of logical possibility or logical proof: “if individuals who affect vesting are alive, then they are assumed to be able to do any act possible for a living person.”[16] Before the late 1970s, having a child after one’s death was illogical and thus not included in the Rule considerations. Now, a post-mortem child is not only logical, it is probable.[17] Moreover, it is now widely accepted that frozen embryos and sperm could remain viable for over twenty-one years after initial cryopreservation.[18] ART success will likely continue its upward trajectory in upcoming years, making it necessary for consistent guidelines—either through judicial precedent or legislation—for applying the Rule to ARTs.[19]

 

Notes

[1] John Chapman Gray, the Rule Against Perpetuities § 201 (4th ed. 1942). There are other approaches to the Rule Against Perpetuities that some jurisdictions use, but this blog only addresses the common law Rule. See Joshua Greenfield, Note, Dad Was Born A Thousand Years Ago? An Examination of Post-Mortem Conception and Inheritance, with a Focus on the Rule Against Perpetuities, 8 Minn. J.L. Sci. & Tech. 277, 577 (2006).

[2] Sharona Hoffman & Andrew P. Morris, Birth After Death: Perpetuities and the New Reproductive Technologies, 38 Ga. L. Rev. 575, 601 (2004).

[3] Id. at 602.

[4] Alan Trounson & Linda Mohr, Human Pregnancy Following Cryopreservation, Thawing and Transfer of an Eight-Cell Embryo, 305 Nature 707, 707 (1983) (“The first pregnancy resulting from a frozen embryo was reported in Australia in 1983.”); Ashley M. Eskew of Developments to Improve in vitro Fertilization, 114 Mo. Med. 156, 156 (May/June 2017) (“[K]nowledge [about IVF] led to the widely acclaimed first live birth of a ‘test tube baby,’ Louise Brown, in England in 1978.”).

[5] Hoffman & Morris, supra note ii, at 593 (“Cryopreservation is the preservation of biological material, such as semen, at very low temperatures.”).

[6] See generally e.g., Laura D. Heard, A Time to Be Born, A Time to Die: Alternative Reproduction and Texas Probate Law, 17 St. Mary’s L.J. 927 (1986); James E. Bailey, An Analytical Framework for Resolving the Issues Raised by the Interaction Between Reproductive Technology and the Law of Inheritance, 47 DePaul L. Rev. 743, 790 (1998); Les A. McCrimmon, Gametes, Embryos and the Life in Being: The Impact of Reproductive Technology on the Rule Against Perpetuities, 34 Real Prop. Prob. & Tr. J. 697 (2000).

[7] Les A. McCrimmon, Gametes, Embryos and the Life in Being: The Impact of Reproductive Technology on the Rule Against Perpetuities, 34 Real Prop. Prob. & Tr. J. 697, 709 (2000); Greenfield, supra note i, at 578.

[8] Hoffman & Morris, supra note ii, at 621 (explaining the Bloom Rule: “By ignoring all cases of posthumously conceived children, the modified Bloom rule protects some interests that should be struck-for example, those where the testator has made a gift with the knowledge that he or she leaves behind stored genetic material and has written a will that violates the Rule”).

[9] Id. at 624–27.

[10] See generally Kathryn Venturatos Lorio, Conceiving the Inconceivable: Legal Recognition of the Posthumously Conceived Child, 34 ACTEC J. 154 (2008).

[11] Hoffman & Morris, supra note ii, at 597.

[12] Id. at 581 (“The maximum length of time that sperm can remain viable is not currently known, but estimates range from twelve years to centuries.”);

[13] Julia Calderone, 10 Years of Fertility Advances, New York Times, https://www.nytimes.com/2020/04/19/parenting/fertility/fertility-advances.html (Apr. 19, 2020).

[14] Id.

[15] G. David Adamson et al., Global Fertility Care with Assisted Reproductive Technology, 120 Fertility & Sterility 473, 473 (2023) (“Since the birth of Louise Brown in 1978, assisted reproductive technology (ART) has brought incredible benefits to millions of people experiencing infertility and wanting to build a family. […] Assisted reproductive technology is now practiced in over a hundred countries globally with an increasing number, from 25 in 1991 to 79 in 2018.”).

[16] Greenfield, supra note i, at 578, 592 (“All forms of the Rule Against Perpetuities depend on the Rule’s traditional common law logical possibility test for at least part of their analysis. Under this approach, any living individual is assumed to be capable of producing children, even at an advanced age. Thus, many of the circumstances that provoke the most criticism of the common law Rule turn on improbable pregnancies among octogenarians and infants.”).

[17] Eskew & Jungheim, supra note iv, at 157–59 (showing ART success rates steadily increasing); Adamson et al., supra note xv, at 474 (discussing current success rates for ART).

[18] Sharona Hoffman & Andrew P. Morris, Currents in Contemporary Ethics, 31 J.L. Med. & Ethics 721, 721 (2003) (“Children have now been conceived with sperm that was frozen for twenty-one years, and with the capability of freezing stem cells of sperm, the possibilities extend perpetually.”); Katheleen R. Guzman, Property, Progeny, Body Part: Assisted Reproduction and the Transfer of Wealth, 31 U. Cal. Davis L. Rev. 193 (1997) (“Continuous technological advances suggest much longer storage periods are possible, thus violating the Rule whenever frozen embryos could be part of a class gift.”).

[19] This is especially true in the aftermath of Dobbs v. Jackson Women’s Health Org., 597 U.S. 215 (2022). Since then, the Alabama Supreme Court recently held that frozen embryos are children, causing some experts to speculate that an embryo itself may be a “life in being.” See Joe Patrice, Alabama Declares Frozen Embryos are Children, Creating Nightmare Rule Against Perpetuities Hypo, Above the Law, https://abovethelaw.com/2024/02/alabama-declares-frozen-embryos-are-children-creating-nightmare-rule-against-perpetuities-hypo/ (Feb. 20, 2024).

A Requiem for Fear, Death, and Dying: Law and Medicine’s Perpetually Unfinished Composition

March 31, 2024
Biotechnology, Ethics, Health Law, Healthcare

Audrey Hutchinson, MJLST Staffer

In the 18th and 19th century, the coffins of newly deceased lay six feet below, but were often outfitted with a novel accessory emerging from the freshly turned earth: a bell hung from an inconspicuous stake, its clapper adorned with a rope that disappeared beneath the dirt.[1] Rather than this display serving as a bygone tradition of the mourning process—some symbolic way to emulate connection with the departed—the bell served a more practical purpose: it was an emergency safeguard against premature burial.[2] The design, and all its variously patented 18th and 19th century designs, draws upon a foundational—and by some biopsychological theories, a biologically imperative—quality: fear of death.[3]

In the mid-1700’s, the French author Jacques Benigne Winslow published a book ominously titled The Uncertainty of the Signs of Death and the Danger of Precipitate Interments and Dissections, marking a decisive and public moment in medical history where death was introduced as something nebulous rather than definite to a highly unsettled public.[4] For centuries, medical tests and parameters had existed by which doctors could “affirmatively” conclude a patient had, indeed, passed.[5] While the Victorian newspapers were riddled with adverts for “safety coffins” in a macabre, but unsurprising expression of capitalism in the wake of mounting cholera deaths and the accompanying rate of premature burial reports, efforts to evade the liminal space of “dying” and the finality of “death” can be seen as far back as ancient Hebrew scriptures, wherein resuscitation attempts via chest compressions are described.[6] Perhaps this is unsurprising: psychologist and experimental theorist Robert C. Bolles conceptualized that fear is “a hypothetical cause [motivation] of behavior” and that its main purpose is to keep organisms alive.[7] Perhaps there has always been a subconscious doubt or suspicion about the finality of death, or perhaps it was human desperation and delusion arising from loss that has left behind an ancient record of fear and subsequent acts of defiance in the face of death still germane today.

Contemporarily we see the fruits of this fear of dying, death, or being somewhere in between in the form of advances in medical technology and legal guidelines. Though death is still commonly understood to be a discrete status—a state one enters but cannot exit—medical and legal definitions have, over time, evolved approaching death more gingerly—the former understanding death as a nuanced scale, the latter drawing hard lines on that scale.[8] Today, 43 states have enacted the Uniform Law Commission’s Uniform Determination of Death Act (“UDDA”).[9] The UDDA requires two distinct standards be met for someone to effectively, and legally, be deemed dead:  1) the irreversible cessation of circulatory and respiratory functions, and 2) the irreversible cessation of all functions of the entire brain, including the brainstem.[10] The UDDA’s legal determination of death, in its bright line language, relies in large part on  “generally accepted medical standards” of the medical practice and practitioner discretion. While the loss of respiratory, circulatory, and total brain death of the entire brain are the common parameters of determining death medically, the UDDA is distinctly “silent on acceptable diagnostic tests [and] procedures.” It is argued that the language is purposeful in creating statutory flexibility in an era of constant scientific and medical research, understanding, and innovation.

As it relates to brain death, the medical approach to determining is a scale that contemplates brain injury/activity and somatic survival, a “continuous biological spectrum”[11] that naturally contemplates not only a patient’s current status, but the possibility and likelihood of both degenerative and improved changes in status. But, as a matter of policy and regulation, the UDDA drew a bright line between the two and called it brain-death. Someone in a permanent vegetative state is not considered braindead, but someone with a necrotic “liquified” brain is. As a result, the medical determination of death is arguably subservient to the legal determination, designating a point of no return–not because the medical professionals see no alternate path, but the law has provided a blindfold required from that point forward.

While this may be an efficient way to ensure people are not denied advanced and improved medical practices, it also means that there is ambiguity and variance from state to state as to the nature of governing factual guidelines and standards. There are practical and policy reasons for this, including maximizing efficacy and reach of organ donation systems and generally preventing strain on healthcare resources and systems; nonetheless, the brightline fails to be so bright. While the Commission could have situated the UDDA such that the determination of legal brain death and medical brain death worked in tandem, being triggered at some distinct moment by certain explicit conditions or after certain standardized medical tests, it did not.

Is that because it will not, or because it simply cannot do so? Today, the standards become increasingly muddied by advancements in technology to prolong life that have, in turn, paradoxically, also prolonged the process of dying—expanding the scope of that liminal space. Artificial means of keeping someone alive where they otherwise could not stay so imperatively creates a discrete state of the act of dying. New legal and medical methods of describing these states have become imperative with lively debate ongoing concerning bridging the medical-legal gap concerning death determination[12]—specifically, the distinction between the “permanent” (will not reverse) and “irreversible” (cannot reverse) cessation of cardiac, respiratory, and neurological function relative to the meaning of a determination of death.[13] James Bernat, a neurologist and academic who examines the convergence of ethics, philosophy, and neurology, is a contemporary advocate calling for reconciliation between medical practice with the law.[14] Dr. Bernat suggests the UDDA’s irreversibility standard—a function that has stopped and cannot be restarted—be replaced with a permanence standard—a function that has stopped, will not restart on its own, and no intervention will be undertaken to restart it.[15] This distinction, in large part, is attempting to address the incongruence of the UDDA’s language that, by the ULC’s own concession, “sets the general legal standard for determining death, but not the medical criteria for doing so.”[16] In effect, in trying to define and characterize death and dying, we have created a dynamic wherein one could be medically dead, but not legally.[17]

Upon his death bed, composer Frédéric Chopin uttered his last words: “The earth is suffocating …. Swear to make them cut me open, so that I won’t be buried alive.”[18] A century and a half later, yet only time will tell if law and medicine can find a way to reconcile the increasingly ambiguous nature of dying and define death explicitly and discretely—no bells required.

Notes

[1] Steven B. Harris, M.D. The Society for the Recovery of Persons Apparently Dead. Cryonics (Sept. 1990) https://www.cryonicsarchive.org/library/persons-apparently-dead/.

[2] Id.

[3] Id.; Shannon E. Grogans et. al., The nature and neurobiology of fear and anxiety: State of the science and opportunities for accelerating discovery, Neuroscience & Biobehavioral Reviews, Volume 151, 2023, 105237, ISSN 0149-7634, https://doi.org/10.1016/j.neubiorev.2023.105237.

[4] Harris, supra note 1.

[5] Id.

[6] Id.

[7] Grogans et. al., supra note 3.

[8] Robert D. Truog, Lessons from the Case of Jahi McMath. The Hastings Center report vol. 48, Suppl. 4 (2018): S70-S73. doi:10.1002/hast.961.

[9] Unif. Determination of death act § 1 (Nat’l Conf. of Comm’n on Unif. L Comm’n. 1981).

[10] Id.

[11] Truog supra at S72.

[12] James L. Bernat, “Conceptual Issues in DCDD Donor Death Determination.” The Hastings Center report vol. 48 Suppl 4 (2018): S26-S28. doi:10.1002/hast.948.

[13] James Bernat, (2010). How the Distinction between ‘Irreversible’ and ‘Permanent’ Illuminates Circulatory-Respiratory Death Determination. The Journal of Medicine and Philosophy. 35. 242-55. 10.1093/jmp/jhq018.

[14] Faculty Database: James L. Bernat, M.D. Dartmouth Geisel School of Medicine https://geiselmed.dartmouth.edu/faculty/facultydb/view.php/?uid=353 (last accessed Oct. 23, 2023).

[15] JD and Angela Turi, Death’s Troubled Relationship With the Law Brendan Parent, AMA J Ethics. 2020;22(12):E1055-1061. doi: 10.1001/amajethics.2020.1055; See also, Bernat JL. Point: are donors after circulatory death really dead, and does it matter? Yes and yes. Chest. 2010;138(1):13-16.

[16] Thaddeus Pope, Brain Death and the Law: Hard Cases and Legal Challenges. The Hastings Center report vol. 48 Suppl. 4 (2018): S46-S48. doi:10.1002/hast.954.

[17] Id.

[18] Death: The Last Taboo – Safety Coffins, Australian Museum (Oct. 20, 2020) https://australian.museum/about/history/exhibitions/death-the-last-taboo/safety-coffins/ (last accessed Oct. 23, 2023).

The Double-Helix Dilemma: Navigating Privacy Pitfalls in Direct-to-Consumer Genetic Testing

November 7, 2023
Administrative Law, Biotechnology, Data, Ethics, Food and Drug Law, Health Law, Healthcare, Privacy

Ethan Wold, MJLST Staffer

Introduction

On October 22, direct-to-consumer genetic testing (DTC-GT) company 23andME sent emails to a number of its customers informing them of a data breach into the company’s “DNA Relatives” feature that allows customers to compare ancestry information with other users worldwide.[1] While 23andMe and other similar DTC-GT companies offer a number of positive benefits to consumers, such as testing for health predispositions and carrier statuses of certain genes, this latest data breach is a reminder that before choosing to opt into these sorts of services one should be aware of the potential risks that they present.

Background

DTC-GT companies such as 23andMe and Ancestry.com have proliferated and blossomed in recent years. It is estimated over 100 million people have utilized some form of direct-to-consumer genetic testing.[2] Using biospecimens submitted by consumers, these companies sequence and analyze an individual’s genetic information to provide a range of services pertaining to one’s health and ancestry.[3] The October 22 data breach specifically pertained to 23andMe’s “DNA Relatives” feature.[4] The DNA Relatives feature can identify relatives on any branch of one’s family tree by taking advantage of the autosomal chromosomes, the 22 chromosomes that are passed down from your ancestors on both sides of your family, and one’s X chromosome(s).[5] Relatives are identified by comparing the customer’s submitted DNA with the DNA of other 23andMe members who are participating in the DNA Relatives feature.[6] When two people are found to have an identical DNA segment, it is likely they share a recent common ancestor.[7] The DNA Relatives feature even uses the length and number of these identical segments to attempt to predict the relationship between genetic relatives.[8] Given the sensitive nature of sharing genetic information, there are often privacy concerns regarding practices such as the DNA Relatives feature. Yet despite this, the legislation and regulations surrounding DTC-GT is somewhat limited.

Legislation

The Health Insurance Portability and Accountability Act (HIPAA) provides the baseline privacy and data security rules for the healthcare industry.[9] HIPAA’s Privacy Rule regulates the use and disclosure of a person’s “protected health information” by a “covered entity.[10] Under the Act, the type of genetic information collected by 23andMe and other DTC-GT companies does constitute “protected health information.”[11] However, because HIPAA defines a “covered entity” as a health plan, healthcare clearinghouse, or health-care provider, DTC-GT companies do not constitute covered entities and therefore are not under the umbrella of HIPAA’s Privacy Rule.[12]

Thus, the primary source of regulation for DTC-GT companies appears to be the Genetic Information Nondiscrimination Act (GINA). GINA was enacted in 2008 for the purpose of protecting the public from genetic discrimination and alleviating concerns about such discrimination and thereby encouraging individuals to take advantage of genetic testing, technologies, research, and new therapies.[13] GINA defines genetic information as information from genetic tests of an individual or family members and includes information from genetic services or genetic research.[14] Therefore, DTC-GT companies fall under GINA’s jurisdiction. However, GINA only applies to the employment and health insurance industries and thus neglects many other potential arenas where privacy concerns may present.[15] This is especially relevant for 23andMe customers, as signing up for the service serves as consent for the company to use and share your genetic information with their associated third-party providers.[16] As a case in point, in 2018 the pharmaceutical giant GlaxoSmithKline purchased a $300 million stake in 23andMe for the purpose of gaining access to the company’s trove of genetic information for use in their drug development trials.[17]

Executive Regulation

In addition to the legislation above, three different federal administrative agencies primarily regulate the DTC-GT industry: the Food and Drug Administration (FDA), the Centers of Medicare and Medicaid services (CMS), and the Federal Trade Commission (FTC). The FDA has jurisdiction over DTC-GT companies due to the genetic tests they use being labeled as “medical devices”[18] and in 2013 exercised this authority over 23andMe by sending a letter to the company resulting in the suspending of one of its health-related genetic tests.[19] However, the FDA only has jurisdiction over diagnostic tests and therefore does not regulate any of the DTC-GT services related to genealogy such as 23andMe’s DNA Relatives feature.[20] Moreover, the FDA does not have jurisdiction to regulate the other aspects of DTC-GT companies’ activities or data practices.[21] CMS has the ability to regulate DTC-GT companies through enforcement of the Clinical Laboratory Improvements Act (CLIA), which requires that genetic testing laboratories ensure the accuracy, precision, and analytical validity of their tests.[22] But, like the FDA, CMS only has jurisdiction over tests that diagnose a disease or assess health.[23]

Lastly, the FTC has broad authority to regulate unfair or deceptive business practices under the Federal Trade Commission Act (FTCA) and has levied this authority against DTC-GT companies in the past. For example, in 2014 the agency brought an action against two DTC-GT companies who were using genetic tests to match consumers to their nutritional supplements and skincare products.[24] The FTC alleged that the companies’ practices related to data security were unfair and deceptive because they failed to implement reasonable policies and procedures to protect consumers’ personal information and created unnecessary risks to the personal information of nearly 30,000 consumers.[25] This resulted in the companies entering into an agreement with the FTC whereby they agreed to establish and maintain comprehensive data security programs and submit to yearly security audits by independent auditors.[26]

Potential Harms

As the above passages illustrate, the federal government appears to recognize and has at least attempted to mitigate privacy concerns associated with DTC-GT. Additionally, a number of states have passed their own laws that limit DTC-GT in certain aspects.[27] Nevertheless, given the potential magnitude and severity of harm associated with DTC-GT it makes one question if it is enough. Data breaches involving health-related data are growing in frequency and now account for 40% of all reported data breaches.[28] These data breaches result in unauthorized access to DTC-GT consumer-submitted data and can result in a violation of an individual’s genetic privacy. Though GINA aims to prevent it, genetic discrimination in the form of increasing health insurance premiums or denial of coverage by insurance companies due to genetic predispositions remains one of the leading concerns associated with these violations. What’s more, by obtaining genetic information from DTC-GT databases, it is possible for someone to recover a consumer’s surname and combine that with other metadata such as age and state to identify the specific consumer.[29] This may in turn lead to identity theft in the form of opening accounts, taking out loans, or making purchases in your name, potentially damaging your financial well-being and credit score. Dealing with the aftermath of a genetic data breach can also be expensive. You may incur legal fees, credit monitoring costs, or other financial burdens in an attempt to mitigate the damage.

Conclusion

As it sits now, genetic information submitted to DTC-GT companies already contains a significant volume of consequential information. As technology continues to develop and research presses forward, the volume and utility of this information will only grow over time. Thus, it is crucially important to be aware of risks associated with DTC-GT services.

This discussion is not intended to discourage individuals from participating in DTC-GT. These companies and the services they offer provide a host of benefits, such as allowing consumers to access genetic testing without the healthcare system acting as a gatekeeper, thus providing more autonomy and often at a lower price.[30] Furthermore, the information provided can empower consumers to mitigate the risks of certain diseases, allow for more informed family planning, or gain a better understanding of their heritage.[31] DTC-GT has revolutionized the way individuals access and understand their genetic information. However, this accessibility and convenience comes with a host of advantages and disadvantages that must be carefully considered.

Notes

[1] https://www.reuters.com/world/us/23andme-notifies-customers-data-breach-into-its-dna-relatives-feature-2023-10-24/#:~:text=%22There%20was%20unauthorized%20access%20to,exposed%20to%20the%20threat%20actor.%22

[2] https://www.ama-assn.org/delivering-care/patient-support-advocacy/protect-sensitive-individual-data-risk-dtc-genetic-tests#:~:text=Use%20of%20direct%2Dto%2Dconsumer,November%202021%20AMA%20Special%20Meeting

[3] https://go-gale-com.ezp3.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[4] https://www.reuters.com/world/us/23andme-notifies-customers-data-breach-into-its-dna-relatives-feature-2023-10-24/#:~:text=%22There%20was%20unauthorized%20access%20to,exposed%20to%20the%20threat%20actor.%22

[5] https://customercare.23andme.com/hc/en-us/articles/115004659068-DNA-Relatives-The-Genetic-Relative-Basics

[6] Id.

[7] Id.

[8] Id.

[9] https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[10] https://www.hhs.gov/sites/default/files/ocr/privacy/hipaa/administrative/combined/hipaa-simplification-201303.pdf

[11] Id.

[12] Id; https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[13] https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008

[14] Id.

[15] https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3035561&blobtype=pdf

[16] https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[17] https://news.yahoo.com/news/major-drug-company-now-access-194758309.html

[18] https://uscode.house.gov/view.xhtml?req=(title:21%20section:321%20edition:prelim)

[19] https://core.ac.uk/download/pdf/33135586.pdf

[20] https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[21] Id.

[22] https://www.law.cornell.edu/cfr/text/42/493.1253

[23] https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[24] https://www.ftc.gov/system/files/documents/cases/140512genelinkcmpt.pdf

[25] Id.

[26] Id.

[27] https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[28] Id.

[29] https://go-gale-com.ezp2.lib.umn.edu/ps/i.do?p=OVIC&u=umn_wilson&id=GALE%7CA609260695&v=2.1&it=r&sid=primo&aty=ip

[30] Id.

[31] Id.

Xenotransplantation: Ethics and Public Policy Need to Catch Up to the Science

March 5, 2022
Administrative Law, Biotechnology, Discrimination, Ethics, Food and Drug Law, Health Law, Medical Devices, New Technology

Claire Colby, MJLST Staffer

In early January, surgeons at the University of Maryland Medical Center made history by successfully transplanting a genetically altered pig heart to a human recipient, David Bennett.  The achievement represents a major milestone in transplantation. The demand for transplantable organs far outpaces the supply, and xenotransplantation–the implantation of non-human tissue into human recipients–could help bridge this gap. In the U.S. alone, more than 106,000 people are on the waiting list for transplants. Legal and ethical questions remain open about the appropriateness of implementing xenotransplants on a large scale. 

The FDA approved the January transplant through an emergency authorization compassionate use pathway because Bennett likely would have died without this intervention. Larger clinical trials will be needed to generate enough data to show that xenotransplants are safe and effective. The FDA will require these trials to show xenotransplantations are non-inferior to human organ transplants. IRB requirements bar interventions where risk outweighs benefits for patients, but accurately predicting and measuring risk is difficult. 

If xenotransplantation becomes standard clinical practice, animal rights proponents may balk at the idea of raising pigs for organs. Far before that point, pre-clinical trials will make heavy use of animal models. Institutional Animal Care and Use Committees (IACUCs) which oversee animal research in universities and medical entities apply a “much lower ethical standard” for animals than human research subjects. Bioethicists apply a “3R” framework for animal subjects research that stresses replacing animal models, reducing animal testing, and refining their use. Because of the inherent nature of xenotransplantation, applying this framework may be near impossible. Ongoing discussions are needed with relevant stakeholders.  

If both human and animal organs are approved for widespread transplant, but human organs prove superior, new allocation policies are needed to determine who gets what. Organ allocation policy is currently dictated by the Organ Procurement and Transplantation Network (OPTN). As it stands, organ transplantation shows inequality across racial groups and financial status. New allocation policies for organs must not reinforce or worsen these disparities. 

Like all medical interventions, patients must be able to provide informed consent for xenotransplantation. The recipient of the altered pig heart had previously been deemed ineligible for a human heart transplant because his heart failure was poorly managed. Reserving experimental interventions, like xenotransplantations, for the sickest patients raises serious ethical concerns. Are these desperate patients truly able to give meaningful consent? If xenotransplantation becomes a common practice, the traditional model of institutional review boards may need updating. Currently, individual institutions maintain their own IRBs. Xenotransplantation of altered animal organs may involve several sites: procurement of the organ, genetic editing, and transplantation may all take place in different locations. A central IRB for xenotransplantation could standardize and streamline this process. 

In all, xenotransplantation represents an exciting new frontier in transplant medicine. Responsibly implementing this innovation will require foresight and parallel innovation in ethics and public policy. 

The Mysterious Disappearance of Deference: What Is the Supreme Court’s Current Relationship to Federal Agencies?

February 7, 2022
Administrative Law, Biotechnology, Copyrights, Ethics

Carly Michaud, MJLST Staffer

The Supreme Court has had no shortage of administrative law cases in the (possibly) final sessions of one of the Court’s administrative law scholars, Justice Stephen Breyer. Yet, Breyer has found himself and his ideological compatriots in the opposition on the topic in which he situates his expertise. In the recent case regarding OSHA’s ability to require COVID-19 vaccines, Breyer’s dissent repeated discusses the proper deference an agency’s determination should be given by the Supreme Court.

Notably absent from the case is any mention of the previous key to the relationship between the courts and federal agencies: Chevron deference. In fact, Chevron U.S.A., Inc. v. National Resources Defense Council, was, (as of a 2014 analysis in the Yale Journal on Regulation) the “Most Cited Supreme Court Administrative Law decision”. While previously considered a niche area, administrative law is now so ubiquitous in practice that as of July 2021, 55 law schools require students take a course in administrative law or one of its mainstays: legislation or statutory interpretation.

In spite of this, Chevron appears nowhere in the discussion of OSHA’s vaccine mandate, nor in the court’s earlier revocation of the CDC’s eviction moratorium. This absence suggests that perhaps this Court has become a body of health experts, relying on their own understanding of COVID-19 to determine whether these agency-created regulations are effective in their mission. Both cases center on whether an agency action to prevent the spread of COVID-19 is within the purview of their empowering statute, and, despite the broad statutory authorities of these agencies to protect the health of Americans, both actions were deemed beyond that authority.

But back to Chevron, has it been abandoned as a standard? Not yet, although there was some discussion of this proposition during the oral argument of American Hospital Association v. Becerra last November. The Court has not released an opinion yet on this case, however the Court of Appeals had previously upheld HHS’s ability to set reembursement rates, per its statutory authority.

In a final thrust of irony, the death knell for Chevron deference may come from a case challenging the very statute and the very agency whose decision-making was at issue in Chevron: the EPA and the Clean Air Act. This is particularly ironic as the EPA administrator whose decision-making was being challenged in Chevron was Anne Gorsuch, the mother of Supreme Court justice and noted antagonist of agency authority: Neil Gorsuch. Yes, in a tale mirroring Hamlet, Neil Gorsuch seems determined to destroy the administrative state that had entangled his mother in various administrative scandals. The latest edition of this showdown between the Gorsuchs and EPA is scheduled for Monday February 28, which will see the Supreme Court hearing arguments in West Virginia v. EPA and its consolidated cases.

This behavior by the Court belies a grave concern both about the continued disempowerment of federal agencies—which have been empowered directly by Congress—at the hands of the unelected judiciary. Further, the most cynical of us may see this as a direct assault on the authority of agencies that some justices may politically disagree with, further disregarding the knowledge of learned experts to push their own political agendas.

You Wouldn’t 3D Print Tylenol, Would You?

October 12, 2021
3-D Printing, Administrative Law, Biotechnology, Ethics, Food and Drug Law, Health Law, Healthcare, Medical Devices

By Mason Medeiros, MJLST Staffer

3D printing has the potential to change the medical field. As improvements are made to 3D printing systems and new uses are allocated, medical device manufacturers are using them to improve products and better provide for consumers. This is commonly seen through consumer use of 3D-printed prosthetic limbs and orthopedic implants. Many researchers are also using 3D printing technology to generate organs for transplant surgeries. By utilizing the technology, manufacturers can lower costs while making products tailored to the needs of the consumer. This concept can also be applied to the creation of drugs. By utilizing 3D printing, drug manufacturers and hospitals can generate medication that is tailored to the individual metabolic needs of the consumer, making the medicine safer and more effective. This potential, however, is limited by FDA regulations.

3D-printed drugs have the potential to make pill and tablet-based drugs safer and more effective for consumers. Currently, when a person picks up their prescription the drug comes in a set dose (for example, Tylenol tablets commonly come in doses of 325 or 500 mg per tablet). Because the pills come in these doses, it limits the amount that can be taken to multiples of these numbers. While this will create a safe and effective response in most people, what if your drug metabolism requires a different dose to create maximum effectiveness?

Drug metabolism is the process where drugs are chemically transformed into a substance that is easier to excrete from the body. This process primarily happens in the kidney and is influenced by various factors such as genetics, age, concurrent medications, and certain health conditions. The rate of drug metabolism can have a major impact on the safety and efficacy of drugs. If drugs are metabolized too slowly it can increase the risk of side effects, but if they are metabolized too quickly the drug will not be as effective. 3D printing the drugs can help minimize these problems by printing drugs with doses that match an individual’s metabolic needs, or by printing drugs in structures that affect the speed that the tablet dissolves. These individualized tablets could be printed at the pharmacy and provided straight to the consumer. However, doing so will force pharmacies and drug companies to deal with additional regulatory hurdles.

Pharmacies that 3D print drugs will be forced to comply with Current Good Manufacturing Procedures (CGMPs) as determined by the FDA. See 21 C.F.R. § 211 (2020). CGMPs are designed to ensure that drugs are manufactured safely to protect the health of consumers. Each pharmacy will need to ensure that the printers’ design conforms to the CGMPs, periodically test samples of the drugs for safety and efficacy, and conform to various other regulations. 21 C.F.R. § 211.65, 211.110 (2020). These additional safety precautions will place a larger strain on pharmacies and potentially harm the other services that they provide.

Additionally, the original drug developers will be financially burdened. When pharmacies 3D print the medication, they will become a new manufacturing location. Additionally, utilizing 3D printing technology will lead to a change in the manufacturing process. These changes will require the original drug developer to update their New Drug Application (NDA) that declared the product as safe and effective for use. Updating the NDA will be a costly process that will further be complicated by the vast number of new manufacturing locations that will be present. Because each pharmacy that decides to 3D print the medicine on-site will be a manufacturer, and because it is unlikely that all pharmacies will adopt 3D printing at the same time, drug developers will constantly need to update their NDA to ensure compliance with FDA regulations. Although these regulatory hurdles seem daunting, the FDA can take steps to mitigate the work needed by the pharmacies and manufacturers.

The FDA should implement a regulatory exception for pharmacies that 3D print drugs. The exemption should allow pharmacies to avoid some CGMPs for manufacturing and allow pharmacies to proceed without being registered as a manufacturer for each drug they are printing. One possibility is to categorize 3D-printed drugs as a type of compounded drug. This will allow pharmacies that 3D print drugs to act under section 503A of the Food Drug & Cosmetic Act. Under this section, the pharmacies would not need to comply with CGMPs or premarket approval requirements. The pharmacies, however, will need to comply with the section 503A requirements such as having the printing be performed by a licensed pharmacist in a state-licensed pharmacy or by a licensed physician, limiting the interstate distribution of the drugs to 5%, only printing from bulk drugs manufactured by FDA licensed establishments and only printing drugs “based on the receipt of a valid prescription for an individualized patient”. Although this solution limits the situations where 3D prints drugs can be made, it will allow the pharmacies to avoid the additional time and cost that would otherwise be required while helping ensure the safety of the drugs.

This solution would be beneficial for the pharmacies wishing to 3D print drugs, but it comes with some drawbacks. One of the main drawbacks is that there is no adverse event reporting requirement under section 503A. This will likely make it harder to hold pharmacies accountable for dangerous mistakes. Another issue is that pharmacies registered as an outsourcing facility under section 503B of the FD&C Act will not be able to avoid conforming to CGMPs unless they withdraw their registration. This issue, however, could be solved by an additional exemption from CGMPs for 3D-printed drugs. Even with these drawbacks, including 3D-printed drugs under the definition of compounded drugs proposes a relatively simple way to ease the burden on pharmacies that wish to utilize this new technology.

3D printing drugs has the opportunity to change the medical drug industry. The 3D-printed drugs can be specialized for the individual needs of the patient, making them safer and more effective for each person. For this to occur, however, the FDA needs to create an exemption for these pharmacies by including 3D-printed drugs under the definition of compounded drugs.

Intellectual Property in Crisis: Does SARS-CoV-2 Warrant Waiving TRIPS?

February 21, 2021
Administrative Law, Biotechnology, COVID-19, Ethics, Food and Drug Law, Health Law, Healthcare, Intellectual Property, Patents

Daniel Walsh, MJLST Staffer

The SARS-CoV-2 virus (which causes the disease COVID-19) has been a massive challenge to public health causing untold human suffering. Multiple vaccines and biotechnologies have been developed to combat the virus at a record pace, enabled by innovations in biotechnology. These technologies, vaccines in particular, represent the clearest path towards ending the pandemic. Governments have invested heavily in vaccine development. In May 2020 the United States made commitments to purchase, at the time, untested vaccines. These commitments were intended to indemnify the manufacture of vaccines allowing manufacturing to begin before regulatory approval was received from the Food and Drug Administration. The United States was not alone. China and Germany, just to name two, contributed heavily to funding the development of biotechnology in response to the pandemic. It is clear that both private and public institutions contributed heavily to the speed with which biotechnology has been developed in the context of the SARS-CoV-2 pandemic. However, there are criticisms that the public-private partnerships underlying vaccine manufacturing and distribution have been opaque. The contracts between governments and manufacturers are highly secretive, and contain clauses that disadvantage the developing world, for example forbidding the donation of extra vaccine doses.

Advanced biotechnology necessarily implicates intellectual property (IP) protections. Patents are the clearest example of this. Patents protect what is colloquially thought of as inventions or technological innovations. However, other forms of IP also have their place. Computer code, for example, can be subject to copyright protection. A therapy’s brand name might be subject to a trademark. Trade secrets can be used to protect things like clinical trial data needed for regulatory approval. IP involved in the pandemic is not limited to technologies developed directly in response to the emergence of SARS-CoV-2. Moderna, for example, has a variety of patents filed prior to the pandemic that protect its SARS-CoV-2 vaccine. IP necessarily restricts access, however, and in the context of the pandemic this has garnered significant criticism. Critics have argued that IP protections should be suspended or relaxed to expand access to lifesaving biotechnology. The current iteration of this debate is not unique; there is a perennial debate about whether it should be possible to obtain IP which could restrict access to medical therapies. Many nations have exceptions that limit IP rights for things like medical procedures. See, e.g., 35 U.S.C. 287(c).

In response to these concerns the waiver of a variety of IP protections has been proposed at the World Trade Organization (WTO). In October 2020 India and South Africa filed a communication proposing “a waiver from the implementation, application and enforcement of Sections 1, 4, 5, and 7 of Part II of the TRIPS Agreement in relation to prevention, containment or treatment of COVID-19.” The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) sets minimum standards for IP standards, acquisition, and enforcement and creates an intergovernmental dispute resolution process for member states. Charles R. McManis, Intellectual Property and International Mergers and Acquisitions, 66 U. Cin. L. Rev. 1283, 1288 (1998). It is necessary to accede to TRIPS in order to join the WTO, but membership in the WTO has significant benefits, especially for developing nations. “Sections 1, 4, 5, and 7 . . .” relate to the protection of copyrights, industrial designs, patents, and trade secrets respectively. Waiver would permit nation states to provide intellectual property protections “in relation to prevention, containment or treatment of COVID-19” that fall below the minimum standard set by the TRIPs Agreement. At time of writing, 10 nations have cosponsored this proposal.

This proposal has been criticized as unnecessary. There is an argument that patents will not enter effect until after the current crisis is resolved, implying they will have no preclusive effect. However, as previously mentioned, it is a matter of fact that preexisting patents apply to therapies that are being used to treat SARS-CoV-2. Repurposing is common in the field of biotechnology where existing therapies are often repurposed or used as platforms, as is the case with mRNA vaccines. However, it is true that therapies directly developed in response to the pandemic are unlikely to be under patent protection in the near future given lag between filing for and receiving a patent. Others argue that if investors perceive biotech as an area where IP rights are likely to be undermined in the event of an emergency, it will reduce marginal investment in vaccine and biotech therapies. Finally, critics argue that the proposal ignores the existing mechanisms in the TRIPS Agreement that would allow compulsory licensing of therapies that nations feel are unavailable. Supporters of the status quo argue that voluntary licensing agreements can serve the needs of developing nations while preserving the investments in innovation made by larger economies.

The waiver sponsors respond that a wholesale waiver would permit greater flexibility in the face of the crisis, and be a more proportionate response to the scale of the emergency. They also assert that the preexisting compulsory licensing provisions are undermined by lobbying against compulsory licensing by opponents of the waiver, though it is unlikely that this lobbying would cease even if a waiver were passed. The sponsors also argue that the public investment implies that any research products are a public good and should therefore be free to the public.

It is unclear how the current debate on TRIPS will be resolved. The voluntary licensing agreements might end up abrogating the need for a wholesale waiver of IP protections in practice rendering the debate moot. However, the WTO should consider taking up the issue of IP protections in a crisis after the current emergency is over. The current debate is a reflection of a larger underlying disagreement about the terms of the TRIPS Agreement. Further, uncertainty about the status of IP rights in emergencies can dissuade investment in the same way as erosion of IP rights, implying that society may pay the costs of decreased investment without reaping any of the benefits.

 

A Cold-Blooded Cure: How COVID-19 Could Decimate Already Fragile Shark Populations

October 10, 2020
Animal Law, Biotechnology, COVID-19, Environmental Law, Ethics, Food and Drug Law, Health Law, Healthcare, Maritime Law, Public Health

Emily Kennedy, MJLST Staffer

Movies like Jaws, Deep Blue Sea, and The Meg demonstrate that fear of sharks is commonplace. In reality, shark attacks are rare, and such incidents have even decreased during the COVID-19 pandemic with fewer people enjoying the surf and sand. Despite their bad, Hollywood-driven reputation sharks play a vital role in the ocean ecosystem. Sharks are apex predators and regulate the ocean ecosystem by balancing the numbers and species of fish lower in the food chain. There are over 500 species of sharks in the world’s oceans and 143 of those species are threatened, meaning that they are listed as critically endangered, endangered, or vulnerable. Sharks are particularly vulnerable because they grow slowly, mature later than other species, and have relatively few offspring. Shark populations are already threatened by ocean fishing practices, climate change, ocean pollution, and the harvesting of sharks for their fins. Sharks now face a new human-imposed threat: COVID-19.

While sharks cannot contract the COVID-19 virus, the oil in their livers, known as squalene, is used in the manufacture of vaccines, including COVID-19 vaccines currently being developed. Shark squalene is harvested via a process known as “livering,” in which sharks are killed for their livers and thrown back into the ocean to die after having their livers removed. The shark squalene is used in adjuvants, ingredients in vaccines that prompt a stronger immune response, and has been used in U.S. flu vaccines since 2016. Approximately 3 million sharks are killed every year to supply squalene for vaccines and cosmetic products, and this number will only increase if a COVID-19 vaccine that uses shark squalene gains widespread use. One non-profit estimates that the demand for COVID-19 vaccines could result in the harvest of over half a million sharks.

Sharks, like many other marine species, are uniquely unprotected by the law. It is easier to protect stationary land animals using the laws of the countries in which their habitats are located. However, ocean habitats largely ungoverned by the laws of any one country. Further, migratory marine species such as sharks may travel through the waters of multiple countries. This makes it difficult to enact and enforce laws that adequately protect sharks. In the United States, the Lacey Act, the Endangered Species Act, and the Magnuson-Stevens Fishery Conservation and Management Act govern shark importation and harvesting practices. One area of shark conservation that has gotten attention in recent years is the removal of shark fins for foods that are considered delicacies in some countries. The Shark Conservation Act was passed in the United States in response to the crisis caused by shark finning practices, in addition to the laws that several states had in place banning the practice. The harvest of shark squalene has not garnered as much attention as of yet, and there are no United States laws enacted to specifically address livering.

Internationally, the Convention on the Conservation of Migratory Species of Wild Animals (CMS) and the International Plan of Action for the Conservation and Management of Sharks (IPOA) are voluntary, nonbinding programs. Many of the primary shark harvesting nations have not signed onto CMS. The Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES) is binding, but there are loopholes and only 13 shark species are listed. In addition to these international programs, some countries have voluntarily created shark sanctuaries.

Nations that have refused to agree to voluntary conservation efforts, that circumvent existing international regulations, and lack sanctuaries leave fragile shark species unprotected and under threat. The squalene harvesting industry in particular lacks transparency and adequate regulations, and reports indicate that protected and endangered shark species end up as collateral damage in the harvesting process. A wide array of regional and international interventions may be necessary to provide sharks with the conservation protections they so desperately need.

Research and development of medical cures and treatments for humans often comes with animal casualties, but research to development of the COVID-19 vaccine can be conducted in a way that minimizes those casualties. There is already some financial support for non-animal research approaches and squalene can also be derived and synthesized from non-animal sources. Shark Allies, the conservation group that created a Change.org petition that now has over 70,000 signatures, suggests that non-shark sources of squalene be used in the vaccine instead, such as yeast, bacteria, sugarcane, and olive oil. These non-animal adjuvant sources are more expensive and take longer to produce, but the future of our oceans may depend on such alternative methods that do not rely on “the overexploitation of a key component of the marine environment.”

Orange Book, Purple Book, Complex Products, and Process Patents

December 23, 2019
Biotechnology, Intellectual Property, Patents

Philip E. Alford, Ph.D., MJLST Staffer

Complex Products and Process Claims

The most economically important pharmaceutical innovations of the past decade have centered around biologics and complex non-biologic products. Biologics are a diverse class of therapeutic products, typically produced via biotechnology or obtained from biological sources. Biologics often contain complex mixtures or large, elaborate molecules that are intricately folded into a specific desired conformation. In many respects, we do not yet have the technology to characterize all the functional elements of these products fully, and sometimes it is not possible to make the products synthetically or according to alternative processes. Even minor variations in biologic manufacturing can result in a product having different properties. Since the manufacturing process may be one of the most accurate ways to describe a biologic, patent strategies for biologics typically give extra emphasis around process patents. Indeed, biologic process claims have proven to be a powerful tool, and process patents have been at the core of the first waves of biosimilar litigation.

Non-biologic drugs can also be so complex as to defy characterization and reproduction. Such products are now referred to as complex products or non-biological complex drugs (NBCDs), as well as “nanomedicine” or “synthetic biologics.” Like biologics, many complex products have the challenge that different manufacturing processes can result in the product having divergent properties. Thus, manufacturing aspects are uniquely important to both complex products and biologics. Where the patent system is involved in the regulatory framework, process patents should play a central role in protecting complex products from generic entry. Yet for complex drug products, FDA does not integrate process patents into the generic entry process.

Despite being difficult to truly reproduce, complex products are nonetheless susceptible to market pressure under Hatch-Waxman-type generic entry 21 USC 355(b)(2) and 355(j), i.e., via Food Drug & Cosmetic Act 505(b)(2) and 505(j) applications. The Hatch-Waxman Act, discussed in more detail below, ingeniously incorporated the patent system as a secondary gatekeeper in FDA’s generic drug approval process. The so-called Orange Book is the nexus uniting two separate regulatory regimes. However, FDA has interpreted that the Orange Book and Hatch-Waxman provisions invoke only on the types of patents that were important for determining infringement of traditional, small molecule drugs, namely, drug and therapeutic use claims. The Orange Book expressly excludes process patents. 21 C.F.R. §314.53.

Although product-by-process claims can be permitted, the resulting product must be novel, and product-by-process claims are not interchangeable with process claims. (For example, see, MPEP 2113 and Judge Newman’s dissent in Abbott Labs. v. Sandoz, Inc, suggesting that process claims and product-by-process claims are held to different validity standards.)

Hatch-Waxman as a political bargain.

When Congress passed the Hatch-Waxman Act was passed in 1984, the Act represented a classic political bargain. The hope was to strike a balance between innovation and competition by strengthening the golden years of brand drugs while facilitating subsequent generic entry. Pioneers of approved new drugs were given up to 5 years of data exclusivity during which FDA would not approve a generic of the drug. Additionally, one of the pioneer’s patents could be extended up to 5 additional years to compensate for lost patent term consumed while seeking FDA approval. In turn, the Act provided a new, streamlined process for drug makers to obtain approval of generic drugs.

A key provision of the Act directs the drug pioneer to identify its patents in the Orange Book. The listed patents must (1) claim the new drug, or (2) claim a method of using the drug, in so far as a claim of infringement could reasonably be asserted if another engaged in the manufacture, use, or sale of the drug. 21 U.S.C. §355(b)(1)(G). The Orange Book thus represents an essential part of the Hatch-Waxman political bargain. Process (manufacturing) patents are expressly excluded from the Orange Book, as are patents relating to packaging, metabolites, or intermediates. 21 C.F.R. §314.53.

The Orange Book lists these patents alongside each FDA approved drug. Before obtaining approval of a generic, the generic drug maker must certify to FDA that the patents listed in the Orange Book are expired, invalid, or will not be infringed by its generic. 21 U.S.C. §355(b)(2)(A) and 21 U.S.C. 355(j)(2)(vii). Under 35 U.S.C. § 271(e)(2), such certifications of invalidity or non-infringement constitutes an act of infringement permitting the pioneer to sue the generic drug maker before the generic ever reaches the market. Prompt litigation can trigger a stay on the generic’s approval. In this manner, the Orange Book serves not only as a mechanism for transparency (informing the public of patent and regulatory exclusivities), but also as a mechanism for litigation. The Orange Book has served both causes well.

As blockbuster biologics began to approach the end of the foreseeable patent life, FDA created a compendium of BLA-approved biological products loosely mirroring the Orange Book, but for biologics instead of drugs. Reverently, FDA named this volume the Purple Book. Unlike the Orange Book, the Purple Book has had no reason to list patents because the generic drug provisions of the Hatch–Waxman Act apply only to drug approvals under 21 U.S.C. §355(b) and 21 U.S.C §355(j). The Biologics Price Competition and Innovation Act of 2009 (BPCIA) provides a framework for approving biosimilars and resolving patent disputes. Instead of referring to a book of approvals and patents, the BPCIA invokes a so-called patent dance exchange of patent information. 42 USC § 262 (l). This patent information includes not only composition and use claims, but also process of manufacture claims. Conceptually, the dance was expected to lead the parties to agree on an initial set of patents to litigate and thus control the tempo and scope of litigation. However, the parties soon recognized that dancing is optional. Sandoz Inc. v. Amgen Inc., 137 S. Ct. 1664. Dance or no dance, the parties ultimately litigate their patent disputes, which often center the methods of manufacturing the biologic product.

As new biologics and complex drug products come to market, process claims are likely to be increasingly important.

Possible Legislation to the Orange Book and Purple Book

This year, Congress considered legislation sponsored by members of the House Committee on Energy and Commerce proposing changes to the way the Purple Book and Orange Book function.

The Purple Book Continuity Act of 2019 proposes that the purple book be updated to list patents generated during the ‘patent dance’ of 42 USC § 262 (l), which would include process patents or any other patent likely to be important in an infringement claim. Any such patents listed in the Purple Book would not function as a regulatory gatekeeper for generics since no mechanism yet exists for the Purple Book to do so. Still, from a transparency point-of-view, it seems like a reasonable choice to have the Purple Book act at least as a compendium of relevant patents. The Orange Book Transparency Act of 2019 proposes a requirement to list the drug substance, drug product, and method of use patents, while also requiring removal of any patents that are improperly listed (presumably including process patents absent any change to 21 C.F.R. §314.53). Although the House Committee on Energy and Commerce sponsored both acts, each take differing approaches to process patents. It seems illogical to insert process patents into the Purple Book, while more tightly excluding process patents from the Orange Book at a time when process claims are increasingly more important to modern therapeutics.

Indeed, FDA has expressly focused on the manufacturing process when trying to understand how a generic relates to a reference complex product. For example, FDA explained that a central part of their inquiry was whether the generic is made according to the same process as the original®, a non-biologic complex product, FDA explained that a central part of their inquiry was whether the generic is made according to the same process as the original. See, also, Bell et al., which discusses FDA’s criteria for approving a generic even when there is no physicochemical or biological characterization technique to establish active ingredient sameness. If such an inquiry is part of FDA’s analysis for permitting the sale of a generic drug, then it should be more than enough to justify listing process patents in the orange book.

If Congress revisits either of these matters, it should adjust the code to include process patents in both the Orange Book and the Purple Book. Listing process patents in the Orange Book would serve a public good, namely, that of transparency, but also would notify competitors of the manufacturing space the pioneer drug company intends to protect. Delaying such litigation until after a possible generic approval is messy for all parties involved. As more medications become too complex to manufacture by alternative routes, the importance of process patents in complex biologic and nonbiologic drugs will only increase.

 

Pacemakers, ICDs, and ICMs – Oh My! Implantable Heart Detection Devices

November 16, 2019
Biotechnology, Data, Ethics, Healthcare, Privacy

Janae Aune, MJLST Staffer

Heart attacks and heart disease kill hundreds of thousands of people in the United States every year. Heart disease affects every person differently based on their genetic and ethnic background, lifestyle, and family history. While some people are aware of their risk of heart problems, over 45 percent of sudden heart cardiac deaths occur outside of the hospital. With a condition as spontaneous as heart attacks, accurate information tracking and reporting is vital to effective treatment and prevention. As in any market, the market for heart monitoring devices is diverse, with new equipment arriving every year. The newest device in a long line of technology is the LINQ monitoring device. LINQ builds on and works with already established devices that have been used by the medical community.

Pacemakers were first used effectively in 1969 when lithium batteries were invented. These devices are surgically implanted under the skin of a patient’s chest and are meant to help control the heartbeat. These devices can be implanted for temporary or permanent use and are usually targeted at patients who experience bradycardia, a slow heart rate. These devices require consistent check-ins by a doctor, usually every three to six months. Pacemakers must also be replaced every 5 to 15 years depending on how long the battery life lasts. These devices revolutionized heart monitoring but involve significant risks with the surgery and potential device malfunctioning.

Implantable cardioverter defibrillators (ICD) are also surgically implanted devices but differ from pacemakers in that they deliver one shock when needed rather than continuous electrode shocks. ICDs are similar to the heart paddles doctors use when trying to stimulate a heart in the hospital – think yelling “charge” and the paddles they use. These devices are used mostly in patients with tachycardia, a heartbeat that is too fast. Implantation of an ICD requires feeding wires through the blood vessels of the heart. A subcutaneous ICD (S-ICD) has been newly developed and gives patients who have structural defects in their heart blood vessels another option of ICDs. Similar to pacemakers, an ICD monitors activity constantly, but will be read only at follow-up appointments with the doctor. ICDs last an average of seven years before the battery will need to be replaced.

The Reveal LINQ system is a newly developed heart monitoring device that records and transmits continuous information to a patient’s doctor at all times. The system requires surgical implantation of a small device known as the insertable cardiac monitor (ICM). The ICM works with another component called the patient monitor, which is a bedside monitor that transmits the continuous information collected by the ICM to a doctor instantly. A patient assistant control is also available which allows the patient to manually mark and record particular heart activities and transmit those in more detail. The LINQ system allows a doctor to track a patient’s heart activity remotely rather than requiring the patient to come in for the history to be examined. Continuous tracking and transmitting allow a patient’s doctor to more accurately examine heart activity and therefore create a more effective treatment approach.

With the development of wearable technology meant to track health information and transmit it to the wearer, the development of devices such as the LINQ system provide new opportunities for technologies to work together to promote better health practices. The Apple Watch series 4 included electrocardiogram monitoring that records heart activity and checks the reading for atrial fibrillation (AFB). This is the same heart activity pacemakers, ICDs, and the LINQ system are meant to monitor. The future capability of heart attack and disease detection and treatment could be massively impacted by the ability to monitor heart behavior in multiple different ways. Between the ability to shock your heart, continuously monitor and transmit information about it, and report to you when your heart rate may be experiencing abnormalities from a watch it seems as if a future of decreased heart problems could be a reality.

With all of these newly developed methods of continuous tracking, it begs the question of how all of that information is protected? Health and heart behavior, which is internal and out of your control, is as personal as information gets. Electronic monitoring and transmission of this data opens it up to cybersecurity targeting. Cybersecurity and data privacy issues with these devices have started to be addressed more fully, however the concerns differ depends on which implantable device a patient has. Vulnerabilities have been identified with ICD devices which would allow an unauthorized individual to access and potentially manipulate the device. Scholars have argued that efforts to decrease vulnerabilities should be focused on protecting the confidentiality, integrity, and availability of information transmitted by implantable devices. The FDA has indicated that the use of a home monitor system could decrease the potential vulnerabilities. As the benefits from heart monitors and heart data continue to grow, we need to be sure that our privacy protections grow with it.

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