Food And Drug Administration Initiatives Research Articles

Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary.

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA-approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke-Margolis Center for Health Policy collaborated with the FDA to host a two-day virtual public workshop entitled "Pharmacodynamic Biomarkers for Biosimilar Development and Approval" on September 20-21, 2021. The public workshop was a forum for global regulators, biopharmaceutical developers, and academic researchers to discuss the current and future role of PD biomarkers in improving the efficiency of biosimilar development and approval. The workshop objectives included: (i) discuss the current and potential future state of leveraging PD biomarkers for biosimilar development and approval; (ii)summarize the FDA's initiatives to advance biosimilar development; (iii) describe stakeholders' experience with PD biomarkers in biosimilar development; and (iv) explain research efforts to promote broader application of PD biomarkers in biosimilar development. This document summarizes presentations and panel discussions from each session of the two-day September 2021 public workshop covering the application of PD biomarkers for biosimilar development.

FDA Initiative for Drug Facts Label for Over-the-Counter Naloxone

BackgroundThe opioid crisis highlights the need to increase access to naloxone, possibly through regulatory approval for over-the-counter sales. To address industry-perceived barriers to such access, the Food and Drug Administration (FDA) developed a model drug facts label for such sales to assess whether consumers understood the key statements for safe and effective use.MethodsIn this label-comprehension study, we conducted individual structured interviews with 710 adults and adolescents, including 430 adults who use opioids and their family and friends. Eight primary end points were developed to assess user comprehension of each of the key steps in the label. Each of these end points included a prespecified target threshold ranging from 80 to 90% that was evaluated through a comparison of the lower boundary of the 95% exact confidence interval.ResultsThe results for performance on six primary end points met or exceeded thresholds, including the steps “Check for a suspected overdose” (threshold, 85%; point estimate [PE], 95.8%; 95% confidence interval [CI], 94.0 to 97.1) and “Give the first dose” (threshold, 85%; PE, 98.2%; 95% CI, 96.9 to 99.0). The lower boundaries for four other primary end points ranged from 88.8 to 94.0%. One exception was comprehension of “Call 911 immediately,” but this instruction closely approximated the target of 90% (PE, 90.3%; 95% CI, 87.9 to 92.4). Another exception was comprehension of the composite step of “Check, give, and call 911 immediately” (threshold, 85%; PE, 81.1%; 95% CI, 78.0 to 83.9).ConclusionsConsumers met thresholds for sufficient understanding of six of eight components of the instructions in the drug facts label for naloxone use and came close on two others. Overall, the FDA found that the model label was adequate for use in the development of a naloxone product intended for over-the-counter sales.

The Role of the Food and Drug Administration in Drug Development: On the Subject of Proarrhythmia Risk.

The Food and Drug Administration (FDA) is responsible for the regulation of the pharmaceutical industry in the interest of protecting public health. The aim of this review was to outline the evolution and current role of the FDA in the development and approval of new drugs. Additionally, we describe current assessments of proarrhythmia risk to illustrate recent FDA initiatives intended to harness information technology to modernize the regulatory process. In order to identify the literature required to produce this review, search tools such as PubMed and Google Scholar were used to locate relevant web pages and articles. The job of the FDA is not only to ensure that high standards for drug efficacy and safety are applied to products available to American consumers and patients but also to balance the lengthy, costly process of maintaining these standards against the pressure to provide access to effective treatments earlier and without surplus expenditures. In order to provide expedited access to the newest effective therapies for critically ill patients in the safest way possible, the FDA has developed several accelerated pathways to fast-track drug approval. Through partnerships with industry and academic institutions, research is being conducted into how information technology can be integrated into the drug development process to improve its cost-effectiveness.

Working Together to Address Women's Health in Research and Drug Development: Summary of the 2017 Women's Health Congress Preconference Symposium.

Historically, women have been underrepresented in clinical research, requiring physicians to extrapolate medical recommendations for women from clinical research done in cohorts consisting predominantly of male participants. While government-funded clinical research has achieved gender parity in phase-3 clinical trials across many biomedical disciplines, improvements are still needed in several facets of women's health research, such as the inclusion of women in early-phase clinical trials, the inclusion of pregnant women and women with physical and intellectual disabilities, the consideration of sex as a biological variable in preclinical research, and the analysis and reporting of sex and gender differences across the full biomedical research continuum. The National Institutes of Health (NIH) Office of Research on Women's Health and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the 25th Annual Women's Health Congress, held in Arlington, VA in April, 2017, to highlight gains made and remaining needs regarding the representation of women in clinical research, to introduce innovative procedures and technologies, and to outline revised policy for future studies. Six speakers presented information on a range of subjects related to the representation of women in clinical research and federal initiatives to advance precision medicine. Topics included the following: the return on investment from the NIH-funded Women's Health Initiative; progress in including women in clinical trials for FDA-approved drugs and products; the importance of clinical trials in pregnant women; FDA initiatives to report drug safety during pregnancy; the NIH-funded All of Us Research Program; and efforts to enhance FDA transparency and communications, including the introduction of Drug Trials Snapshots. This article summarizes the major points of the presentations and the discussions that followed.

FDA Benchmark Medical Device Flow Models for CFD Validation.

Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal's Web site (www.asaiojournal.com) to listen.

The Essentials of Medical Device Inventory Tracking

As the cost and complexity of medical equipment increase, healthcare technology management (HTM) professionals find themselves more and more in need of tools to track inventory maintenance and location, particularly for commonly used portable devices. However, the computerized maintenance management systems widely used in hospitals are not designed to help locate moveable devices, and many healthcare facilities do not make use of tracking technology that has been available for many years. This article reviews some of the central issues in medical inventory management and the more common challenges HTM professionals face. Several examples of successful tracking system implementation also are discussed.

Public‐private partnerships as driving forces in the quest for innovative medicines

BackgroundDespite progress in translational research, we are still falling short in developing the innovative medicines required to address major public health needs. Furthermore, the failure rate, time, and cost required for registration of a new drug are pushing the economics of the industry to the breaking point. New models of drug development based on collaborative endeavours are badly needed to improve this dire situation.FindingsIn 2004, the US Food and Drug Administration (FDA) introduced the Critical Path Initiative with the intent of modernizing drug development by implementing public-private partnerships (PPP) to share data, expertise, and resources. In response to FDA’s initiative, in the following year the non-profit Critical Path Institute (C-Path) was formed. At the same time, the National Institutes of Health (NIH) Public-Private Partnership program was established. In Europe, the Innovative Medicines Initiative (IMI) supported jointly by the European Union and the European Federation of Pharmaceutical Industries and Associations was launched in 2008. These independent efforts have a common long-term objective, namely to facilitate the emergence of innovative medicines by developing new tools for drug discovery, new indicators for drug efficacy or safety, and new approaches for patient stratification. Herein, we present evidence that PPP already exert a positive impact on the drug development process.ConclusionsPublic-private partnerships represent attractive means to leverage resources dispersed across industry, academia, and voluntary health organizations in order to address multiple challenges of drug development in an era of constrained resources and increased regulatory pressure.

FUNCTIONAL CLAIMS: ANTIOXIDANTS AND CLAIMS

Health claims that characterize the relationship between a substance (e.g., a food or food component) and a disease (e.g., cancer or cardiovascular disease) or health-related condition (e.g., hypertension) require premarket approval by organizations as the Turkey Agriculture and Rural Affairs Ministry, Europena Food Safety Authority (EFSA), the US Food and Drug Administration (FDA) and Codex Alimentarius Commision (CAC) to be included on the labels of conventional foods and dietary supplements. Before 1990, health claims about disease were not allowed on food labels. However, in the late 1980s, emerging evidence about relationships between diet and health generated interest among consumers and the food industry about conveying this information on the food label. Qualified health claims are based on less scientific evidence than authorized health claims and must be accompanied by a disclaimer or otherwise qualified in their wording. Qualified health claims were first issued for the labeling of dietary supplements after several court decisions regarding First Amendment issues and were later expanded to conventional foods as the result of a major FDA initiative in 2003. In this study, health claims used for fruit and vegetable juices depend on national and international regulations, importance of health claims for the fruit juice industry and consumer responses to health claims in fruit juice products were surveyed.

What’s Next After 50 Years of Psychiatric Drug Development

This article discusses changes in psychiatric drug development from a US Food and Drug Administration (FDA) standpoint. It first looks back at changes that have been influenced by regulatory process and then looks forward at FDA initiatives that are likely to affect psychiatric drug development in the future. FDA protects the public health by ensuring the safety and efficacy of drug products introduced into the US market. FDA works with drug sponsors during development, and, when applications are submitted, reviews the safety and efficacy data and the proposed labeling. Drug advertising and promotion and postmarketing surveillance also fall within FDA's responsibility. Among the many changes in psychiatric drug development over the past 50 years, several have been particularly influenced by FDA. Populations studied have expanded diagnostically and demographically, and approved psychiatric indications have become more focused on the clinical entities actually studied, including in some cases specific symptom domains of recognized syndromes. Trial designs have become increasingly complex and informative, and approaches to data analysis have evolved to better model the reality of clinical trials. This article addresses 2 general areas of innovation at FDA that will affect psychiatric drug development in years to come. Several programs falling under the general heading of the Critical Path Initiative, ie, biomarkers, adaptive design, end-of-phase 2A meetings, and data standards, are described. In addition, a number of important safety initiatives, including Safety First, the Sentinel Initiative, the Safe Use Initiative, and meta-analysis for safety, are discussed.

Systematic Survey of Therapeutic Trials for Metastatic Colorectal Cancer: Room for Improvement in the Critical Pathway

The current strategy of drug development has been criticized as being highly inefficient. In 2004, the US Food and Drug Administration (FDA) released recommendations to improve this process, including a push for increased use of enrichment trials. It is unclear to what extent aspects of this "Critical Path Initiative" have been adopted in trial designs in metastatic colorectal cancer. A systematic review was conducted of actively enrolling treatment trials in metastatic colorectal cancer. Trials were identified from the National Cancer Institute's clinicaltrials.gov and Investigative Drug Branch databases. Trials were categorized based on the number of prior treatments allowed, phase of the trial, agent mechanism of action, and FDA approval status of agents under investigation. One hundred two trials are enrolling, with a combined enrollment goal of more than 20,000 patients. Thirteen percent of trials investigated an agent not yet FDA-approved for any oncology indication. The most common study design was a phase II study limited to previously untreated patients; compared with the remaining trials, these phase II trials were more than 10 times more likely to only use agents FDA-approved for colorectal cancer. Three percent of patients were enrolled onto trials enriched for tumor characteristics that were hypothesized to improve clinical benefit. Current clinical trials for metastatic colorectal cancer are deficient in the investigation of agents directed at a novel therapeutic target, overuse phase II studies of FDA-approved agents, and fail to incorporate enrichment trial designs as encouraged by the FDA initiative.

Introduction to the new prescription drug labeling by the Food and Drug Administration

The revised prescription drug labeling developed by the Food and Drug Administration (FDA) is described. A new FDA final rule, "Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products," became effective in June 2006. The rule is part of FDA's initiative to manage the risks of medical product use and minimize adverse events. The new labeling reorders and reorganizes sections found in the previous labeling format. A label is now divided into highlights of prescribing information, contents of the full prescribing information (FPI), and the FPI. The highlights section is a half-page summary of the information that health care practitioners most commonly refer to and view as most important. This section contains cross-references to details in the FPI section. The contents section serves as a navigational tool that references all the sections in the FPI. The FPI section has been revised as to content, format, and order to make information clearer and more usable. FDA has instituted a flexible implementation schedule that phases in the new labeling requirements; more time to achieve compliance is provided for older products. The revision of labeling for products approved or submitted for approval under an abbreviated new drug application (ANDA) depends on the labeling of the listed drug referenced in the ANDA. The new requirements do not apply to nonprescription drug products. FDA has designed new labeling to help health care practitioners easily find, read, and convey information important for the safe and effective use of prescription drugs.

An Academic ECG Core Lab Perspective of the FDA Initiative for Digital ECG Capture and Data Management in Large-Scale Clinical Trials

Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a new drug or procedure. The Food and Drug Administration (FDA) has presented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information on new medical therapies. This FDA initiative has led to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiography manufacturers, and the academic as well as the nonacademic ECG core labs. In this article, we present a broad-based viewpoint from two groups of academic ECG core labs, the Alliance of Academic ECG Core Labs and the Virtual Electronic ECG Corelab International Consortium. We have chosen to widen the perspective from using digitized ECG data in safety trials only, as addressed by the FDA guideline draft, to a discussion on the possibilities and the potential problems when using digitized ECG data also in large clinical trials focusing on efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense.

Quality assessment programs for dietary supplements.

In the US, consumers and healthcare professionals have been forced to depend on self-regulation by the dietary supplement industry for product quality, consistency, potency, and purity, a system that has yielded mixed results at best. To characterize the current state of product quality verification in the dietary supplement industry and review recent developments and future plans to improve supplement safety and regulation. Studies describing the quality of dietary supplements are reviewed, along with recent Food and Drug Administration (FDA) plans to improve supplement regulation. Several independent dietary supplement quality certification programs are described and evaluated. Quality control standards for dietary supplements run the gamut from good to nonexistent. Contamination, false labeling, and incomplete labeling are not uncommon problems--as are significant discrepancies in disintegration, dissolution, and in vitro release characteristics of various dietary supplements. The need for improved regulation has led to plans for increased FDA involvement through enforcement of good manufacturing practices and truths in labeling. Meanwhile, independent product certification companies have emerged and provide some reassurances; however, they possess several limitations as well. Until proposed FDA initiatives are finalized and implemented, certification programs can help provide assurances of safety and assist in product selection. Although they do not testify to effectiveness (and may even inadvertently mislead some consumers), certification programs may help curb what has been called "the Wild West nature of the dietary supplement industry."