FDA-regulated Products Research Articles

Food and Drug Administration Issues Strategic Plan for Risk Communication

The US Food and Drug Administration (FDA) in September issued a strategic plan that outlines a framework for the agency to provide information about FDA-regulated products to health care professionals, patients and consumers in a usable and timely fashion, and which also describes how the agency oversees industry communications.

Use of Field-Portable XRF Analyzers for Rapid Screening of Toxic Elements in FDA-Regulated Products

Analytical instrumentation continues its amazing evolution, especially in regard to generating ever more sensitive, faster, and reliable measurements. Perhaps the most difficult challenges are making these instruments small enough to use in the field, equipping them with well-designed software that facilitates and simplifies their use by nonexperts while preserving enough of their analytical capabilities to render them useful for a wide variety of applications. Perhaps the most impressive and underappreciated example of instruments that meet these criteria are field-portable X-ray fluorescence (XRF) analyzers. In the past, these analyzers have been routinely used for environmental applications (lead in paint and soil, metal particulates in air samples collected onto filters), geology studies (ore and soil analysis, precious metal identification), and recycling industries (alloy identification). However, their use in the analysis of toxic elements in food, food ingredients, dietary supplements, and medicinal and herbal products, especially within the FDA and regulatory environments, has been surprisingly limited to date. Although XRF will not replace atomic spectrometry techniques such as ICP-MS for sub-parts per million level analyses, it offers a number of significant advantages including minimal sample preparation, high sample throughputs, rapid and definitive identification of many toxic elements, and accurate quantitative results. As should be obvious from many recent news reports on elevated levels of toxic elements in children's lunchboxes, toys, and supplements, field-portable XRF analyzers can fill a very important niche and are becoming increasingly popular for a wide variety of elemental analysis applications. This perspective begins with a brief review of the theory of XRF to highlight the underlying principle, instrumentation, and spectra. It includes a discussion of various analytical figures of merit of XRF to illustrate its strengths and limitations compared to existing methods such as ICP-MS. It concludes with a discussion of a number of different FDA applications and case studies in which XRF has been used to screen, identify, and in some cases quantify toxic elements in various products. This work clearly demonstrates that XRF analyzers are an exceedingly valuable tool for routine and nonroutine elemental analysis investigations, both in the laboratory and in the field. In the future, it is hoped that both field-portable and laboratory-grade XRF analyzers will see more widespread use for investigational and forensic-type applications of food and other regulated consumer products.

GET READY FOR NANOTECH FOOD

NANOSCALE MATERIALS have the potential to improve the taste, color, flavor, texture, and consistency of food. Innovators in the food industry are using them to encapsulate dietary supplements to increase the absorption and bioavailability of nutrients. And they’re adding these new materials to food packaging to create a stronger mechanical barrier, kill microbes, detect chemical and microbial contamination, and facilitate the traceability of foods. Despite the promises of nanotechnology for food applications, a growing number of people are beginning to question whether government oversight and consumer awareness are sufficient to prevent the kind of public backlash that occurred with genetically modified foods and food irradiation. At a daylong public meeting in September, the Food & Drug Administration called upon stakeholders to help the agency better understand concerns related to the safety and effectiveness of nanoscale materials in FDA-regulated products, including food, food packaging, and dietary ...

Leave Regulation to the FDA

Former FDA Commissioner Donald Kennedy recently opined (“Misbegotten preemptions,” Editorial, 2 May, p. [585][1]) that makers of FDA-regulated products should be subject to lawsuits in state courts when things go wrong, even if they have followed FDA's rules to the letter. I disagree. The

Personalized Medicine? An Update on Warfarin (Coumadin) Labeling

specifically CYP2C9*2 and CYP2C9*3, have demonstrated a need for a reduced dose of warfarin. 5 Patients with polymorphisms of the VKORC1 gene have demonstrated a spectrum of responses to warfarin, ranging from resistance to reduced dosage need. 2,5 Warfarin is a specific inhibitor of the vitamin K epoxide reductase (VKOR), which is encoded by VKORC1 gene. 5 Some patients may possess both poly morphisms, leading to severe over anticoagulation if not treated properly. The approved new labeling marks the start of a new era of pharmacy, pharmacogenomics or personalized medicine. The FDA started a new program 3 years ago called Critical Path Initiative that “is [the] FDA’s effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured.” 6

Talking about…

Talking about…

Hipaa’s Latest Privacy Rule

The Health Insurance Portability and Accountability Act of 1996 final medical information privacy rule was published on August 14, 2002, in the Federal Register. This version modifies the rule issued under the Clinton administration in 2000. Some key changes were made to the provisions for marketing, consent and notice, uses and disclosures regarding FDA-regulated products and activities, incidental use and disclosure of health information, authorization requirements, minimum necessary standards exemption, business associates contracts, research authorization to use protected health information, and a limited data set for use in research, public health, and health care operations. Privacy protection groups criticize the changes as a significant weakening of privacy standards, whereas health care business groups see the changes as making the rule more “workable.”

Gender-based differences in the toxicity of pharmaceuticals--the Food and Drug Administration's perspective.

Women experience more adverse reactions to treatment with therapeutic drugs than men. Theories proposed to explain this include overdosing, different pharmacokinetics and pharmacodynamics, women are more likely to report adverse events than men, or women take more medications than men. Food and Drug Administration (FDA) Office of Women's Health (OWH) funds research to promote including women in clinical trials and understanding the biology of sex-related differences in the safety of FDA-regulated products. Including women in clinical trials advances the understanding of drug efficacy and safety in women by providing information on drug dosing, pharmacokinetics, and pharmacodynamics. A Baysian statistical analysis of sex differences in adverse events showed that although about the same number of adverse events were reported for men and women, those reported for women were more serious. One example of a sex difference in the toxicity of pharmaceuticals is the drug-induced cardiac arrhythmia, torsades de point. OWH funded studies in animals and humans to investigate the mechanism behind this sex difference. These studies demonstrated that shortening the QT interval increases the risk of developing torsades and that androgens protect against torsades by slowing cardiac repolarization and prolonging the QT interval. Understanding the mechanisms behind other reported sex-related differences in adverse drug effects requires additional research. The preliminary studies conducted to date suggest that this sex-related difference is likely to be a multifactorial problem requiring information from several fields of study. Ideally, individuals at risk for developing an adverse event should be identified prior to therapeutic intervention. The OWH plans to fund more studies to investigate the role of hormonal variations on drug metabolism and drug-drug interactions. Animal and in vitro model systems are needed to fully understand the mechanism of how gender influences drug toxicity.

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin lighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits, grains, coffee, tea, beer, and wine. While there are few reports of adverse health effects associated with the production and use of HQ, a great deal of research has been conducted with HQ because it is a metabolite of benzene. Physicochemical differences between HQ and benzene play a significant role in altering the pharmaco-kinetics of directly administered when compared with benzene-derived HQ. HQ is only weakly positive in in vivo chromosomal assays when expected human exposure routes are used. Chromosomal effects are increased significantly when parenteral or in vitro assays are used. In cancer bioassays, HQ has reproducibly produced renal adenomas in male F344 rats. The mechanism of tumorigenesis is unclear but probably involves a species-, strain-, and sex-specific interaction between renal tubule toxicity and an interaction with the chronic progressive nephr-opathy that is characteristic of aged male rats. Mouse liver tumors (adenomas) and mononuclear cell leukemia (female F344 rat) have also been reported following HQ exposure, but their significance is uncertain. Various tumor initiation/promotion assays with HQ have shown generally negative results. Epidemiological studies with HQ have demonstrated lower death rates and reduced cancer rates in production workers when compared with both general and employed referent populations. Parenteral administration of HQ is associated with changes in several hematopoietic and immunologic endpoints. This toxicity is more severe when combined with parenteral administration of phenol. It is likely that oxidation of HQ within the bone marrow compartment to the semiquinone or p-benzoquinone (BQ), followed by covalent macromolecular binding, is critical to these effects. Bone marrow and hematologic effects are generally not characteristic of HQ exposures in animal studies employing routes of exposure other than parenteral. Myelotoxicity is also not associated with human exposure to HQ. These differences are likely due to significant route-dependent toxicokinetic factors. Fetotoxicity (growth retardation) accompanies repeated administration of HQ at maternally toxic dose levels in animal studies. HQ exposure has not been associated with other reproductive and developmental effects using current USEPA test guidelines. The skin pigment lightening properties of HQ appear to be due to inhibition of melanocyte tyrosinase. Adverse effects associated with OTC use of HQ in FDA-regulated products have been limited to a small number of cases of exogenous ochronosis, although higher incidences of this syndrome have been reported with inappropriate use of unregulated OTC products containing higher HQ concentrations. The most serious human health effect related to HQ is pigmentation of the eye and, in a small number of cases, permanent corneal damage. This effect has been observed in HQ production workers, but the relative contributions of HQ and BQ to this process have not been delineated. Corneal pigmentation and damage has not been reported at current exposure levels of <2 mg/m3. Current work with HQ is being focused on tissue-specific HQ-glutathione metabolites. These metabolites appear to play a critical role in the renal effects observed in F344 rats following HQ exposure and may also be responsible for bone marrow toxicity seen after parenteral exposure to HQ or benzene-derived HQ.

Conference on FDA-Regulated Products and Pregnant Women

Conference on FDA-Regulated Products and Pregnant Women