The US FDA's New Rule for Regulating Laboratory-Developed Tests.

This Viewpoint discusses potential benefits and obstacles regarding US Food and Drug Administration (FDA) oversight of laboratory-developed tests.

The RACE Act and Pediatric Trials of Adult Cancer Drugs.

BACKGROUND AND OBJECTIVES: Adult cancer drugs have historically been exempted from pediatric testing requirements. In 2017, Congress passed the Research to Accelerate Cures and Equity (RACE) for Children Act to expand mandatory pediatric testing to cancer drugs; the law took effect in 2020. With this study, we sought to evaluate how the pediatric testing of molecularly targeted adult cancer drugs changed after the RACE Act. METHODS: In this retrospective cohort study, we used publicly available Food and Drug Administration data to compare pediatric post-approval requirements, trials, and trial characteristics, including timing, in adult cancer drugs before and after the RACE Act. RESULTS: Between 2017 and 2024, the Food and Drug Administration approved 61 adult cancer drugs with molecular targets relevant to pediatric cancer; 40 were submitted before 2020, and 21 were submitted after 2020. The 40 pre-RACE Act drugs were associated with no pediatric post-approval requirements, whereas the 21 post-RACE Act drugs were associated with 15 pediatric post-approval testing requirements. Approximately two-thirds (26/40, 65%) of pre-RACE Act drugs and 57% (12/21) of post-RACE Act drugs were evaluated in pediatric trials. Among pre-RACE Act cancer drugs, pediatric trials were initiated a median of 0.04 years after approval (interquartile range: -3.3 to 1.9 years), whereas post-RACE Act trials were initiated a median of 2.8 years before approval (interquartile range: -4.3 to 0.3 years). CONCLUSIONS: The RACE Act has been associated with greater numbers of pediatric post- approval testing requirements and the earlier initiation of pediatric trials, although early pediatric trial rates appear unchanged. Formalizing pediatric testing requirements may lead to the timely completion of pediatric studies to the benefit of pediatric patients with cancer.

Public Perceptions of the Food and Drug Administration's Regulatory Authority Over Synthetic Nicotine on Twitter: Observational Study.

BACKGROUND: The Omnibus Budget Bill, known as H. R. 2471, passed through Congress on March 10, 2022, and was eventually signed by President Biden on March 15, 2022. This bill amended the Federal Food, Drug, and Cosmetic Act granting the Food and Drug Administration (FDA) regulatory authority over synthetic nicotine. OBJECTIVE: This study aims to examine the public perceptions of the Omnibus Bill that regulates synthetic nicotine products as tobacco products on Twitter (rebranded as X). METHODS: Through the X streaming application programming interface, we collected and identified 964 tweets related to the Omnibus Bill on synthetic nicotine between March 8, 2022, and April 13, 2022. The longitudinal trend was used to examine the discussions related to the bill over time. An inductive method was used for the content analysis of related tweets. By hand-coding 200 randomly selected tweets by 2 human coders respectively with high interrater reliability, the codebook was developed for relevance, major topics, and attitude to the bill, which was used to single-code the rest of the tweets. RESULTS: Between March 8, 2022, and April 13, 2022, we identified 964 tweets related to the Omnibus Bill regulating synthetic nicotine. Our longitudinal trend analysis showed a spike in the number of tweets related to the bill during the immediate period following the bill's introduction, with roughly half of the tweets identified being posted between March 8 and 11, 2022. A majority of the tweets (497/964, 51.56%) had a negative sentiment toward the bill, while a much smaller percentage of tweets (164/964, 17.01%) had a positive sentiment toward the bill. Around 31.43% (303/964) of all tweets were categorized as objective news or questions about the bill. The most popular topic for opposing the bill was users believing that this bill would lead users back to smoking (145/497, 29.18%), followed by negative implications for small vape businesses (122/497, 24.55%) and government or FDA mistrust (94/497, 18.91%). The most popular topic for supporting the bill was that this bill would take a dangerous tobacco product targeted at teens off the market (94/164, 57.32%). CONCLUSIONS: We observed a more negative sentiment toward the bill on X, largely due to users believing it would lead users back to smoking and negatively impact small vape businesses. This study provides insight into public perceptions and discussions of this bill on X and adds valuable information for future regulations on alternative nicotine products.

Real-world evidence to support regulatory submissions: A landscape review and assessment of use cases.

Real-world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non-oncology therapeutic areas. Most were for indications in adults only (N = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single-arm trials. External data to support single-arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site-based charts. Endpoints in oncology use cases commonly included overall survival, progression-free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision-making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross-sector efforts are needed to further improve the quality and utility of RWE in regulatory decision-making.

Controversial FDA Decision Authorizes Menthol-Flavored E-Cigarettes Despite Risks to Youth.

This Medical News story examines the controversy surrounding the FDA's first authorization of flavored e-cigarettes, in this case menthol.

Approval of the First Nonprescription Oral Contraceptive Pill.

In July 2023, the U.S. Food and Drug Administration approved Opill (norgestrel 0.075 mg), a progestin-only tablet to prevent pregnancy to be used without a prescription. Although progestin-only birth control pills were approved in 1973, it has taken 50 years for the first oral contraceptive pills to be sold over the counter. In this column, I review the evidence on the barriers to access oral contraceptive pills, the efficacy, preferences and support of a nonprescription progestin-only pill, the cost, and policy implications for health insurance coverage. I conclude with recommendations from professional organizations on over-the-counter access to hormonal contraception.

Variability in Constituents of E-Cigarette Products Containing Nicotine Analogues.

This study characterizes and quantifies constituents in 2 e-cigarette products to assess product consistency and inform future risk assessments.

Congress Must Update FDA Regulations for Medical AI.

This JAMA Forum discusses pending legislation in the US House and Senate and the history of the "firm-based approach" the US Food and Drug Administration (FDA) could use when regulating artificial intelligence (AI) medical devices to augment patient care.

A roadmap for affordable genetic medicines.

Twenty genetic therapies have been approved by the US Food and Drug Administration to date, a number that now includes the first CRISPR genome-editing therapy for sickle cell disease-CASGEVY (exagamglogene autotemcel, Vertex Pharmaceuticals). This extraordinary milestone is widely celebrated owing to the promise for future genome-editing treatments of previously intractable genetic disorders and cancers. At the same time, such genetic therapies are the most expensive drugs on the market, with list prices exceeding US$4 million per patient. Although all approved cell and gene therapies trace their origins to academic or government research institutions, reliance on for-profit pharmaceutical companies for subsequent development and commercialization results in prices that prioritize recouping investments, paying for candidate product failures and meeting investor and shareholder expectations. To increase affordability and access, sustainable discovery-to-market alternatives are needed that address system-wide deficiencies. Here we present recommendations of a multidisciplinary task force assembled to chart such a path. We describe a pricing structure that, once implemented, could reduce per-patient cost tenfold and propose a business model that distributes responsibilities while leveraging diverse funding sources. We also outline how academic licensing provisions, manufacturing innovation and supportive regulations can reduce cost and enable broader patient treatment.

Evaluation of the Generic Drug User Fee Act (GDUFA) Program for Fiscal Years 2013-2022.

The effectiveness of the regulatory initiatives, strategies, and incentives put forth in the first two authorizations of the Generic Drug User Fees Act (GDUFA) were evaluated using factors including the number of Abbreviated New Drug Application (ANDA) withdrawals and first-cycle approvals. GDUFA was originally authorized in 2012 for FY 2013-2017 (GDUFA I) and reauthorized for FY 2018-2022 (GDUFA II). ANDA approvals were analyzed from the Drugs @ FDA database covering 2013-2022. From the applications, the approval time, dosage form and route of administration (ROA), product indication, market status of the product, first generic status, company and company size filing the ANDA were noted. Despite the COVID pandemic, there was more than a 40% increase in ANDA approvals during GDUFA II relative to GDUFA I. Oral and parenteral drugs were the two leading categories of approved generics during both iterations of GDUFA. There was more than a 120% increase in withdrawn applications during GDUFA II, which reflects the partial refund that is now offered to incentivize companies to withdraw inadequate applications prior to review. This also appears to have contributed to an increase in the number of first-cycle approvals, which increased by 100% between GDUFA I and II. Due to the COVID-19 public health emergency, there was a decrease in activity within the generic drug program and market. Therefore, it is important to consider this impact when observing actual trends from this study.

The Origins of "Confidential Commercial Information" at the FDA.

This Viewpoint reviews regulations regarding FDA's handing of confidential commercial information, explains how these regulations serve as a barrier to disclosure of information in the interest of public health, and suggests how information could be carefully shared to improve health outcomes and advance research.