The unsteady state and inertia of chemical regulation under the US Toxic Substances Control Act.

After 40 years, the 1976 US Toxic Substances Control Act (TSCA) was revised under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. Its original goals of protecting the public from hazardous chemicals were hindered by complex and cumbersome administrative burdens, data limitations, vulnerabilities in risk assessments, and recurring corporate lawsuits. As a result, countless chemicals were entered into commercial use without toxicological information. Few chemicals of the many identified as potential public health threats were regulated or banned. This paper explores the factors that have worked against a comprehensive and rational policy for regulating toxic chemicals and discusses whether the TSCA revisions offer greater public protection against existing and new chemicals.

FDA Approval and Regulation of Pharmaceuticals, 1983-2018.

Importance: US law requires testing of new drugs before approval to ensure that they provide a well-defined benefit that is commensurate with their risks. A major challenge for the US Food and Drug Administration (FDA) is to achieve an appropriate balance between rigorous testing and the need for timely approval of drugs that have benefits that outweigh their risks. Objective: To describe the evolution of laws and standards affecting drug testing, the use of new approval programs and standards, expansions of the role and authority of the FDA, and changes in the number of drugs approved from the 1980s to 2018. Evidence: Sources of evidence included principal federal laws and FDA regulations (1962-2018) and FDA databases of approved new drugs (1984-2018), generic drugs (1970-2018), biologics (1984-2018), and vaccines (1998-2018); special development and approval programs (Orphan drug [1984-2018], Fast-Track [1988-2018], Priority Review and its predecessors [1984-2018], Accelerated Approval [1992-2018], and Breakthrough Therapy [2012-2018]); expanded access (2010-2017) and Risk Evaluation and Mitigation Strategies (2008-2018); and user fees paid to the FDA by industry (1993-2018). Findings: From 1983 to 2018, legislation and regulatory initiatives have substantially changed drug approval at the FDA. The mean annual number of new drug approvals, including biologics, was 34 from 1990-1999, 25 from 2000-2009, and 41 from 2010-2018. New biologic product approvals increased from a median of 2.5 from 1990-1999, to 5 from 2000-2013, to 12 from 2014-2018. The median annual number of generic drugs approved was 136 from 1970 to the enactment of the Hatch-Waxman Act in 1984; 284 from 1985 to the enactment of the Generic Drug User Fee Act in 2012; and 588 from 2013-2018. Prescription drug user fee funding expanded from new drugs and biologics in 1992 to generic and biosimilar drugs in 2012. The amount of Prescription Drug User Fee Act fees collected from industry increased from an annual mean of $66 million in 1993-1997 to $820 million in 2013-2017, and in 2018, user fees accounted for approximately 80% of the salaries of review personnel responsible for the approval of new drugs. The proportion of drugs approved with an Orphan Drug Act designation increased from 18% (55/304) in 1984-1995, to 22% (82/379) in 1996-2007, to 41% (154/380) in 2008-2018. Use of Accelerated Approval, Fast-Track, and Priority Review for new drugs has increased over time, with 81% (48/59) of new drugs benefiting from at least 1 such expedited program in 2018. The proportion of new approvals supported by at least 2 pivotal trials decreased from 80.6% in 1995-1997 to 52.8% in 2015-2017, based on 124 and 106 approvals, respectively, while the median number of patients studied did not change significantly (774 vs 816). FDA drug review times declined from more than 3 years in 1983 to less than 1 year in 2017, but total time from the authorization of clinical testing to approval has remained at approximately 8 years over that period. Conclusions and Relevance: Over the last 4 decades, the approval and regulation processes for pharmaceutical agents have evolved and increased in complexity as special programs have been added and as the use of surrogate measures has been encouraged. The FDA funding needed to implement and manage these programs has been addressed by expanding industry-paid user fees. The FDA has increasingly accepted less data and more surrogate measures, and has shortened its review times.

Regulating Homeopathic Products - A Century of Dilute Interest.

In 2015, U.S. government agencies began considering greater regulation of both homeopathic drugs and the advertising of such products. These actions came after more than a century of missed opportunities to regulate homeopathic medicines.

Peter Bourne's drug policy and the perils of a public health ethic, 1976-1978.

As President Jimmy Carter's advisor for health issues, Peter Bourne promoted a rational and comprehensive drug strategy that combined new supply-side efforts to prevent drug use with previously established demand-side addiction treatment programs. Using a public health ethic that allowed the impact of substances on overall population health to guide drug control, Bourne advocated for marijuana decriminalization as well as increased regulations for barbiturates. A hostile political climate, a series of rumors, and pressure from both drug legalizers and prohibitionists caused Bourne to resign in disgrace in 1978. We argue that Bourne's critics used his own public health framework to challenge him, describe the health critiques that contributed to Bourne's resignation, and present the story of his departure as a cautionary tale for today's drug policy reformers.

Hatch-Waxman Turns 30: Do We Need a Re-Designed Approach for the Modern Era?

In 1984, Congress passed the Hatch-Waxman Act, which catalyzed the creation of the modem generic drug industry. Generic drugs today account for eighty-four percent of all prescriptions dispensed, but less than twenty percent of drug costs. Despite this success, numerous problems in the generic drug market have emerged. Some involve the deliberate manipulation of the Hatch-Waxman system, while others have arisen more unexpectedly, such as the Supreme Court's 2011 decision in Pliva v. Mensing that could undermine consumer confidence in generic drugs. We discuss these emerging challenges and propose updates to the Hatch-Waxman Act to continue support for the timely emergence of safe generic drugs.

MEDICINAL CANNABIS LAW REFORM: LESSONS FROM CANADIAN LITIGATION.

This editorial reviews medicinal cannabis litigation in Canada's superior courts between 1998 and 2015. It reflects upon the outcomes of the decisions and the reasoning within them. It identifies the issues that have driven Canada's jurisprudence in relation to access to medicinal cannabis, particularly insofar as it has engaged patients' rights to liberty and security of the person. It argues that the sequence of medicinal schemes adopted and refined in Canada provides constructive guidance for countries such as Australia which are contemplating introduction of medicinal cannabis as a therapeutic option in compassionate circumstances for patients. In particular, it contends that Canada's experience suggests that strategies calculated to introduce such schemes in a gradualist way, enabling informed involvement by medical practitioners and pharmacists, and that provide for safe and inexpensive accessibility to forms of medicinal cannabis that are clearly distinguished from recreational use and unlikely to be diverted criminally maximise the chances of such schemes being accepted by key stakeholders.

Waiting for the opportune moment: the tobacco industry and marijuana legalization.

CONTEXT: In 2012, Washington State and Colorado legalized the recreational use of marijuana, and Uruguay, beginning in 2014, will become the first country to legalize the sale and distribution of marijuana. The challenge facing policymakers and public health advocates is reducing the harms of an ineffective, costly, and discriminatory "war on drugs" while preventing another public health catastrophe similar to tobacco use, which kills 6 million people worldwide each year. METHODS: Between May and December 2013, using the standard snowball research technique, we searched the Legacy Tobacco Documents Library of previously secret tobacco industry documents (http://legacy.library.ucsf.edu). FINDINGS: Since at least the 1970s, tobacco companies have been interested in marijuana and marijuana legalization as both a potential and a rival product. As public opinion shifted and governments began relaxing laws pertaining to marijuana criminalization, the tobacco companies modified their corporate planning strategies to prepare for future consumer demand. CONCLUSIONS: Policymakers and public health advocates must be aware that the tobacco industry or comparable multinational organizations (eg, food and beverage industries) are prepared to enter the marijuana market with the intention of increasing its already widespread use. In order to prevent domination of the market by companies seeking to maximize market size and profits, policymakers should learn from their successes and failures in regulating tobacco.

Tragedy, transformation, and triumph: comparing the factors and forces that led to the adoption of the 1860 Adulteration Act in England and the 1906 Pure Food and Drug Act in the United States.

The 1860 Adulteration Act in England and the 1906 Pure Food and Drug Act in the United States were two of the earliest pieces of legislation to provide generalized regulation of food and drugs on a national scale. While significant scholarly attention has been given to explaining the factors and forces that led to the passage of each Act independent of the other, few books or articles have directly compared the similar individuals and events that led to the adoption of both Acts. This paper attempts to fill that gap. Through a comparative examination, this paper reveals that four main components were key to the national pure food and drug movements in both countries: individuals who crusaded for national adulteration legislation; tragedies that shocked the public into calling for reform; press and publicity that was willing and able to bring the evils of adulteration to the forefront of the public mind; and a transformation of the social, political, and economic systems, which created atmospheres conducive to reform. This paper aims to shed new light on the 1860 Adulteration Act and the 1906 Pure Food and Drug Act--two acts that derive their importance not just from the effect that they directly had on the regulation of food and drugs but also as some of the earliest examples of western governments coming to recognize the need for national regulation to protect the public from harm and coming to embrace their changing role as spearheads of modern regulatory states.

[Major milestones for European pharmaceutical policy]. / Les grandes étapes de l'Europe du medicament.

Under the 1985 White Paper on the completion of the single market, several pharmaceutical harmonisation measures were unanimously adopted, in favor of biotech products and on pricing transparency, legal status of prescription, wholesale distribution and advertising. The European pharmaceutical harmonisation was extended to Norway and Iceland, to new accession member states and through major international conferences with the US and Japan (ICH). Starting in 1995, the European medicines agency has produced an efficient marketing authorisation system for new human and veterinary medicines. The system was extended to pediatric medicines and advanced therapies. The monitoring of drug adverse effects (pharmacovigilance) has been gradually strengthened.