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\"Formaldehyde, borax, salicylic acid. Today, these chemicals are used in embalming fluids, cleaning supplies, and acne medications. But in 1900, they were routinely added to food that Americans ate from cans and jars. Often products weren't safe because unregulated, unethical companies added these and other chemicals to trick consumers into buying spoiled food or harmful medicines. Chemist Harvey Washington Wiley recognized these dangers and began a relentless thirty-year campaign to ensure that consumers could purchase safe food and drugs, eventually leading to the creation of the U.S. Food and Drug Administration, or FDA. Acclaimed nonfiction and Sibert Honor winning author Gail Jarrow uncovers this intriguing history in her trademark style that makes the past enthrallingly relevant for today's young readers.\"--Amazon.

After US Food and Drug Administration (FDA) approval of a new drug, sponsors can submit additional clinical data to obtain supplemental approval for use for new indications. To characterize pivotal trials supporting recent supplemental new indication approvals of drugs and biologics by the FDA and to compare them with pivotal trials that supported these therapeutics' original indication approvals. This is a cross-sectional study characterizing pivotal trials supporting supplemental indication approvals by the FDA between 2017 and 2019 and pivotal trials that supported these therapeutics' original indication approvals. Data analysis was performed from August to October 2020. Number and design of pivotal trials supporting both supplemental and original indication approvals. From 2017 to 2019, the FDA approved 146 supplemental indications for 107 therapeutics on the basis of 181 pivotal efficacy trials. The median (interquartile range) number of trials per supplemental indication was 1 (1-1). Most trials used either placebo (77 trials [42.5%; 95% CI, 35.6%-49.8%]) or active comparators (65 trials [35.9%; 95% CI, 29.3%-43.1%]), and most of these multigroup trials were randomized (141 trials [99.3%; 95% CI, 96.0%-100.0%]) and double-blinded (106 trials [74.5%; 95% CI, 66.6%-81.0%]); 80 trials (44.2%; 95 CI, 37.2%-51.5%) used clinical outcomes as the primary efficacy end point. There was no difference between oncology therapies and those approved for other therapeutic areas to have supplemental indication approvals be based on at least 2 pivotal trials (11.5% vs 20.6%; difference, 9.1%; 95% CI, 2.9%-21.0%; P = .10). Similarly, there was no difference in use of randomization (98.3% vs 100.0%; difference, 1.7%; 95% CI, 1.6%-5.0%; P = .43) among multigroup trials, although these trials were less likely to be double-blinded (50.8% vs 92.3%; difference, 41.5%; 95% CI, 27.4%-55.5%; P < .001); overall, these trials were less likely to use either placebo or active comparators (64.9% vs 86.7%; difference, 21.8% 95% CI, 9.8%-33.9%; P < .001) or to use clinical outcomes as their primary efficacy end point (27.5% vs 61.1%; difference, 33.6%; 95% CI, 14.1%-40.9%; P < .001) and were longer (median [interquartile range], 17 [6-48] weeks vs 95 [39-146] weeks). Original approvals were more likely than supplemental indication approvals to be based on at least 2 pivotal trials (44.0% [95% CI, 33.7%-42.6%] vs 15.8% [95% CI, 10.7%-22.5%]; difference, 28.2%; 95% CI, 17.6%-39.6%; P < .001) and less likely to be supported by at least 1 trial of 12 months' duration (27.6% [95% CI, 17.9%-35.0%] vs 54.8% [95% CI, 46.7%-62.6%]; difference, 27.2%; 95% CI, 14.5%-37.8%; P < .001). Pivotal trial designs were otherwise not significantly different. These findings suggest that the number and design of the pivotal trials supporting supplemental indication approvals by the FDA varied across therapeutic areas, with the strength of evidence for cancer indications weaker than that for other indications. There was little difference in the design characteristics of the pivotal trials supporting supplemental indication and original approvals.

In the wake of publicity and congressional attention to drug safety issues, the Food and Drug Administration (FDA) requested the Institute of Medicine assess the drug safety system. The committee reported that a lack of clear regulatory authority, chronic underfunding, organizational problems, and a scarcity of post-approval data about drugs' risks and benefits have hampered the FDA's ability to evaluate and address the safety of prescription drugs after they have reached the market. Noting that resources and therefore efforts to monitor medications' risk-benefit profiles taper off after approval, The Future of Drug Safety offers a broad set of recommendations to ensure that consideration of safety extends from before product approval through the entire time the product is marketed and used.

The FDA and the Case of Ketek Since the FDA approved the drug Ketek (telithromycin), concerns have arisen about both safety and fraud. Dr. David Ross writes that there are lessons to be learned from an examination of the events surrounding the approval of this product. Dr. David Ross discusses the FDA review process for the antibiotic Ketek, problems with data integrity, and the “culture of approval” at the FDA. Dr. Ross is a clinical assistant professor at George Washington University School of Medicine and Health Sciences, Washington, D.C., and a former medical reviewer for the FDA. Three years ago, the Food and Drug Administration (FDA) approved the drug Ketek (telithromycin), lauding it as the first of a new class of antimicrobial agents that circumvent antibiotic resistance. Since then, Ketek has been linked to dozens of cases of severe liver injury, been the subject of a series of increasingly urgent safety warnings, and sparked two Congressional investigations of the FDA's acceptance of fraudulent safety data and inappropriate trial methods when it reviewed the drug for approval. As a former FDA physician who was involved in the Ketek review, I believe there are lessons to be learned from . . .

The Food and Drug Administration (FDA) lacks certain authorities and is persistently underresourced to fulfill its mission of protecting the public by ensuring that foods are safe, wholesome, sanitary, and properly labeled. Particularly concerning gaps exist in pre- and postmarket oversight of food ingredients that are often found in ultraprocessed foods. Numerous substances either have evidence of harm or are unknown to the FDA and the public. Additional authorities and resources are necessary. User fees have been successfully implemented to provide resources to the FDA for other programs under its purview. This legal and policy analysis evaluates the FDA's food-related authorities that would be amenable to a new user fee program. It reviews policy domains where new or enhanced user fees may be warranted. We find that a new comprehensive FDA user fee program for food may benefit industry and generate targeted new resources to strengthen the agency's oversight.

This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future. A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates. While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines. The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy. The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200–800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, “high” vs “low”), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80–125%) in the analysis population. This study is registered with ClinicalTrials.gov\\, number NCT01713777. Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98–103, Cmax 90% CI 99–105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study. Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate. American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration.

The FDA Reauthorization Act of 2017 includes the sixth version of the Prescription Drug User Fee Act. User fees have accelerated drug approvals in the context of inadequate funding of the FDA, and industry now pays 75% of the costs of the scientific review of drugs.

Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted. To describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel cancer drugs approved for the first time between 2000 and 2016. This comparative effectiveness study analyzed randomized clinical trials and single-arm clinical trials of novel drugs approved for the first time to treat any type of cancer. Approval packages were obtained from drugs@FDA, a publicly available database containing information on drug and biologic products approved for human use in the US. Data from January 2000 to December 2016 were included in this study. Regulatory and clinical trial characteristics were described. For randomized clinical trials, summary treatment outcomes for overall survival, progression-free survival, and tumor response across all therapies were calculated, and median absolute survival increases were estimated. Tumor types and regulatory characteristics were assessed separately. Between 2000 and 2016, 92 novel cancer drugs were approved by the FDA for 100 indications based on data from 127 clinical trials. The 127 clinical trials included a median of 191 participants (interquartile range [IQR], 106-448 participants). Overall, 65 clinical trials (51.2%) were randomized, and 95 clinical trials (74.8%) were open label. Of 100 indications, 44 indications underwent accelerated approval, 42 indications were for hematological cancers, and 58 indications were for solid tumors. Novel drugs had mean hazard ratios of 0.77 (95% CI, 0.73-0.81; I2 = 46%) for overall survival and 0.52 (95% CI, 0.47-0.57; I2 = 88%) for progression-free survival. The median tumor response, expressed as relative risk, was 2.37 (95% CI, 2.00-2.80; I2 = 91%). The median absolute survival benefit was 2.40 months (IQR, 1.25-3.89 months). In this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry.

Under US President Donald Trump, defunct economic arguments about prescription drugs are coming to the fore. His advisers contend that today's system is a bad deal. They want to undo regulations that require companies to show that a medical product actually works before it is sold. The advisers argue that removing the burden of large, lengthy clinical trials will cut costs and reduce delays, and that the marketplace can be trusted to sort good drugs from bad ones.