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This brief report covers recent advances in cannabis and cannabinoid regulation and drug approval. The popularity of cannabis and cannabinoid products continues to rise, and these products are available for the majority of the population in the United States to purchase as easily as alcohol. Although many states have approved programs and research licenses, these activities and products all remain federally illegal. The solution may be for the United States to offer multiple pathways for product approval that adapt to the diversity of the products and the needs of the consumer. Multiple pathways for market approval would protect public health, whether the public is using cannabis and cannabinoids as a medicine, a wellness product, or as a recreational substance.
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Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general.

Introduction: The first biopharmaceuticals were developed 30 years ago. Biopharmaceuticals differ significantly from small molecule therapeutics (SMTs). Because of such differences, it was expected that classical preclinical safety evaluation procedures applied to SMTs would not predict the adverse effects of biopharmaceuticals. Therefore, until sufficient experience was gained, the preclinical safety evaluation of biopharmaceuticals was carried out on a case-by-case basis. 30 years of experience has since expanded the knowledge base in this area, in the hope to design a preclinical safety evaluation procedure suited to biopharmaceuticals., Areas Covered: This review describes how the preclinical safety evaluation of biopharmaceuticals has evolved. It shows that, as result of the risk-averse behavior of regulators and industry, classical procedures were taken as starting point although state-of-the-art knowledge on biopharmaceuticals was directed towards creating a new procedure, driven by the specific properties of biopharmaceuticals., Expert Opinion: Current preclinical safety evaluation guidance of biopharmaceuticals is criticized because it employs a checkbox approach. The adverse effects induced by biopharmaceuticals are on-target or immune system-induced, therefore, the preclinical safety evaluation should not be standardized, but rather driven by product specific safety concerns.

Biosimilars are a new class of medicine. The European Medicines Agency has pioneered the legal, regulatory, and scientific framework for approval of these products. One of the foundational principles of the European framework is that biosimilars are expected to be similar, not identical, to the innovator biologics they seek to copy. This contrasts with the legal, regulatory, and scientific framework for copies of chemical medicines, generics, which are based on the expectation that the innovator and generic drug substance are identical. This article reviews the European biosimilar regulatory pathway and reviews some of the clinical data being made public following the approval, rejection, and withdrawal of biosimilar marketing applications.

It is a continual challenge trying to improve the quality of prescribing while concurrently trying to address increasing pharmaceutical development, utilization and expenditure. National and regional reforms and initiatives in Sweden have moderated growth in ambulatory drug expenditure to 2.7% per annum in recent years despite increasing volumes. National reforms include mandatory generic substitution and value-based pricing alongside devolution of drug budgets to the regions. Regional initiatives include strengthening the role of the regional Drug and Therapeutic Committees, further budget devolution as well as strategies incorporating prescribing guidance and monitoring coupled with financial incentives. The extent and nature of the regional initiatives vary depending on their characteristics. In this article, we compare initiatives undertaken in two major counties, Stockholm and Ostergötland, and their outcomes. Outcomes include annual drug budget savings while achieving agreed quality as well as increased adherence to prescribing targets and guidance; the latter associated with savings. Appraising these multifaceted reforms can provide guidance to other countries and regions in view of their diversity. Future steps must incorporate measures to improve the utilization of new expensive drugs, which should include horizon scanning and forecasting activities as well as post-launch activities involving monitoring of prescribing and registries. This may well require cooperation with other European countries.

The banned use of antimicrobial growth promoters resulted in a considerably decreased use of antimicrobials in food animal production in Sweden (65%), Denmark (47%), Norway (40%) and Finland (27%). The current prevalence of antimicrobial resistance in animal bacterial populations is also considerably lower than in some other countries in the EU. In the swine production, no or limited effect was found in the finisher production (>25 to 30 kg). Temporary negative effects occurred during the post weaning period (7-30 kg). In Denmark, the cost of production from birth to slaughter per pig produced increased by approximately 1.0 euro with a high variability between pig producers. In the broiler production the termination had no significant negative effect on animal health and welfare or on production economy.

During the late 1990s, all use of antibiotic growth promotors for production animals was gradually banned in Denmark. At the same time, the legislation on prescription of medicine was tightened and registration of usage became mandatory. Following the ban, the prevalence of diarrhoea - often caused by Lawsonia intercellularis - increased, which led to an expected increased use of therapeutic antibiotics. However, the consumption never reached the same amount of antibiotics as distributed before the ban. As a consequence, production performance dropped with a reduction of 18 g to 50 g per day in daily gain and mortality increased by an extra 0.6% to 1.5%, especially in the weaner period. The cost of this is at least from 1 to 3 US dollars per animal. No reliably substitute to antibiotic has been found yet, but improvement of the diet and management on all levels are important factors for compensation. Further investigations in this area are called for in the future.

The physician who prescribes controlled substances is faced with an array of laws, regulatory policies, and professional attitudes about their use. Prescriptions for these scheduled drugs are furthermore monitored by the pharmacists who dispense them. Certain drugs, such as the opioids and the benzodiazepines, are considered so potentially abusive that special programs have been recommended to track the behavior of physician prescribers. Multiple copy programs have been implemented in some states. More recent proposals recommend electronic data transfer (EDT) of pharmacy information to centralized processing points so that misprescribing physicians and doctor-shopping patients can be identified. Regulators concerned about physician behavior and confronted by demands of nonphysicians to prescribe controlled substances may find EDT a good solution. Physicians should be concerned about being censured for misprescribing, because such actions may lead to inclusion in the National Practitioner Data Bank. With all of the regulatory concerns about controlled substances, those physicians who would employ long-term opioid therapy for their chronic pain patients must follow certain basic guidelines to be able to defend themselves against allegations of deviant professional behavior. Such procedures as conducting a history and physical examination, maintaining a written treatment plan, consulting with knowledgeable colleagues, and assessing for addictive behavior can provide the practitioner with safeguards.