Analyses of consumers' preferences and of the correspondence between direct and indirect label claims and the fatty acid profile of milk in large retail chains in northern Italy.

Combined results from 2 survey studies were used to obtain information useful for the industries and retailers involved in the milk production and selling chain in North Italy. The first survey identified different clusters of fluid milk purchasers by examining their preferences and attitudes toward 12 intrinsic-extrinsic and credence milk attributes, by applying best-worst scaling methodology, whereas the second survey characterized the fatty acid (FA) profiles of commercial milk sold by large-scale retailers to verify the correspondence between the actual FA profile and the direct and indirect claims on the labels. To summarize information about the FA profile of milk, which may be considered an advanced attribute of milk quality, the milk FA index (MFAI) was calculated for each milk sample. A total of 130 milk samples (around 85% of the labels in northern Italy) and a total of 502 participants who answered a face-to-face questionnaire were considered in the 2 surveys. The milk samples were 13.1% organic, 9.2% certified as being of mountain origin, and over 50% noncertified but linked to cow grazing or to a mountain environment on their labels. The FA profiles showed a wide range of variation, with saturated FA ranging from 63.4 to 71.8, and polyunsaturated FA from 2.76 to 5.85. The FA profile and MFAI index of certified milk (organic or mountain-derived) were significantly different from the profiles of noncertified milk, whereas no correspondence was observed between the retail price and milk quality. When ranked on the basis of MFAI, which proved to be a good discriminating tool, the certified milks presented a bimodal distribution, indicating that certification does not always guarantee a real difference. The consumers chose milk considering the origin of the product, brand, expiration date, and process certification as the most important attributes, whereas they rated price and organic certification as the least important attributes. The study showed that about 20% of the consumers had a high propensity to buy milk on the basis of its quality. However, this attribute is often incorrectly indicated or not indicated at all on the milk label, with misleading images or claims that do not correspond to the actual FA quality of the milk. Having a clear index that offers information about the FA profile could thus be an interesting tool to improve the awareness of buyers and to valorize and differentiate milk products.

Dietary Supplement Ingredient Database (DSID) and the Application of Analytically Based Estimates of Ingredient Amount to Intake Calculations.

OBJECTIVE: We describe the purpose of the Dietary Supplement Ingredient Database (DSID), the statistical methodology underlying online calculators of analytically verified supplement content estimates, and the application and significance of DSID label adjustments in nutritional epidemiology. BACKGROUND AND HISTORY: During dietary supplement (DS) manufacturing, many ingredients are added at higher than declared label amounts, but overages are not standardized among manufacturers. As a result, researchers may underestimate nutrient intakes from DSs. The DSID provides statistical tools on the basis of the results of chemical analysis to convert label claims into analytically predicted ingredient amounts. These adjustments to labels are linked to DS products reported in NHANES. RATIONALE: Tables summarizing the numbers of NHANES DS products with ingredient overages and below label content show the importance of DSID adjustments to labels for accurate intake calculations. RECENT DEVELOPMENTS: We show the differences between analytically based estimates and labeled content for vitamin D, calcium, iodine, caffeine, and omega-3 (n-3) fatty acids and their potential impact on the accuracy of intake assessments in large surveys. Analytical overages >20% of label levels are predicted for several nutrients in 50-99% of multivitamin-mineral products (MVMs) reported in NHANES: for iodine and selenium in adult MVMs, for iodine and vitamins D and E in children's MVMs, and for iodine, chromium, and potassium in nonprescription prenatal MVMs. Predicted overages of 10-20% for calcium can be applied to most MVMs and overages >10% for folic acid in the vast majority of adult and children's MVMs. FUTURE DIRECTIONS: DSID studies are currently evaluating ingredient levels in prescription prenatal MVMs and levels of constituents in botanical DSs. CONCLUSIONS: We estimate that the majority of MVM products reported in NHANES have significant overages for several ingredients. It is important to account for nonlabeled additional nutrient exposure from DSs to better evaluate nutritional status in the United States.

The Acceptability Limit in Food Shelf Life Studies.

Despite its apparently intuitive nature, the acceptability limit is probably the most difficult parameter to be defined when developing a shelf life test. Although it dramatically affects the final shelf life value, it is surprising that discussion on its nature has been largely neglected in the literature and only rare indications about the possible methodologies for its determination are available in the literature. This is due to the fact that the definition of this parameter is a consumer- and market-oriented issue, requiring a rational evaluation of the potential negative consequences of food unacceptability in the actual market scenario. This paper critically analyzes the features of the acceptability limit and the role of the decision maker. The methodologies supporting the choice of the acceptability limit as well as acceptability limit values proposed in the literature to calculate shelf life of different foods are reviewed.

Evaluation of dispensaries' cannabis flowers for accuracy of labeling of cannabinoids content.

BACKGROUND: Cannabis policies have changed drastically over the last few years with many states enacting medical cannabis laws, and some authorizing recreational use; all against federal laws. As a result, cannabis products are marketed in dispensaries in different forms, most abundantly as flowers intended for smoking and sometimes vaping. All samples used in this study were obtained directly from law enforcement. The sample collection process was facilitated and funded by the National Marijuana Initiative (NMI), part of the High-Intensity Drug Trafficking Area (HIDTA) program. This initial report focuses on cannabis flowers. Similar studies with other cannabis products will be the subject of a future report. METHODS: A total of 107 Δ9-THC cannabis flower samples were collected by law enforcement from adult commercial use cannabis dispensaries, located in three different states (Colorado, Oregon, and California) and analyzed in this study for cannabinoid concentration. Samples were analyzed by GC-FID following our previously published procedure. DISCUSSION: The label claims for total Δ9-THC content ranged from 12.04 to 58.20% w/w, while GC-FID results showed a concentration ranging from 12.95 to 36.55% w/w. Of the evaluated 107 products, only 32 samples have Δ9-THC content within ± 20% of the labeled content. However, the remaining 75 samples were found to be out of the ± 20% acceptance criteria. The degree of agreement for the tested samples using ± 20% tolerance with label claims was only 30%. The results of this study indicate that there is a need for more stringent regulations to ensure that product labeling is accurate, as 70% of the evaluated products did not meet the ± 20% acceptance criteria. This highlights the importance of healthcare professionals and patients being vigilant about the Δ9-THC content, as inaccurate labeling of cannabis products could potentially result in adverse health effects. Furthermore, there is a pressing need for more rigorous regulation of commercial cannabis products in the United States.

Label accuracy of unregulated cannabidiol (CBD) products: measured concentration vs. label claim.

BACKGROUND: The legalization of hemp in the USA has led to tremendous growth in the availability of hemp-derived products, particularly cannabidiol (CBD) products. The lack of regulatory oversight in this industry has resulted in the marketing and sale of CBD products with questionable ingredients and quality. The aim of the current study was to examine the CBD content in 80 commercially available hemp-derived CBD products purchased from online and local retailers. Epidiolex® was also included in the study as a positive control. METHODS: Hemp-derived CBD products were selected to represent products readily available to residents of Central Kentucky. The samples were comprised of local and national brands produced in a variety of locations inside and outside of Kentucky. The products were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the analytical findings were compared to the label claims for CBD content. Descriptive statistics and normal-based confidence intervals were calculated using Microsoft Excel. RESULTS: The label claims for CBD content ranged from 7.5 to 60 mg/mL, while LC-MS/MS analysis detected a range of 2.9 to 61.3 mg/mL. Of the 80 products evaluated, 37 contained CBD concentrations that were at least ± 10% different than the concentration listed on the label (range of 0.9 to 30.6 mg/mL from label claim) - 12 products contained < 90%, while 25 products contained > 110%. The degree of concordance for the samples tested using ± 10% tolerance from label claim was 54%. CONCLUSIONS: These data suggest that additional regulation is required to ensure label accuracy as nearly half of the products in this study were not properly labelled (i.e., not within a ± 10% margin of error). Consumers and practitioners should remain cautious of unregulated and often-mislabeled CBD products due to the risks of taking too much CBD (e.g., drug-drug interactions, liver enzyme elevations, increased side effects) and the consequences of taking too little (e.g., no clinical benefits due to underdosing). The results of this study support the continued need for good manufacturing practices and testing standards for CBD products.

Continuous direct compression: Development of an empirical predictive model and challenges regarding PAT implementation.

In this study, an empirical predictive model was developed based on the quantitative relationships between blend properties, critical quality attributes (CQA) and critical process parameters (CPP) related to blending and tableting. The blend uniformity and API concentration in the tablets were used to elucidate challenges related to the processability as well as the implementation of PAT tools. Thirty divergent ternary blends were evaluated on a continuous direct compression line (ConsiGma™ CDC-50). The trials showed a significant impact of the impeller configuration and impeller speed on the blending performance, whereas a limited impact of blend properties was observed. In contrast, blend properties played a significant role during compression, where changes in blend composition significantly altered the tablet quality. The observed correlations allowed to develop an empirical predictive model for the selection of process configurations based on the blend properties, reducing the number of trial runs needed to optimize a process and thus reducing development time and costs of new drug products. Furthermore, the trials elucidated several challenges related to blend properties that had a significant impact on PAT implementation and performance of the CDC-platform, highlighting the importance of further process development and optimization in order to solve the remaining challenges.

New Drug and Biologics Approvals in 2019: A Systematic Analysis of Patient Experience Data in FDA Drug Approval Packages and Product Labels.

BACKGROUND: The FDA Patient-Focused Drug Development Initiative was launched to ensure the incorporation of the patient voice into drug development and evaluation. Since 2017, the FDA must publish a statement outlining patient experience data (PED) considered in the approval of new drugs. This study investigated the presence and role of PED in drug approval and translation into product label claims. METHODS: PED reported in approval packages of the 48 drugs approved by FDA's Center for Drug Evaluation and Research in 2019 was identified and categorized. PED in the form of clinical outcome assessments (COAs) was characterized by endpoint positioning and outcome. The product labels were analyzed for PED-related claims. RESULTS: PED was reported as relevant for 39 of 48 (81.3%) drugs approved in 2019. COAs were the predominant PED type; other PED was identified for only 9 (18.8%) drugs, and none included qualitative or patient preference studies. COAs were the only type of PED for which associated claims were identified in the product labels. 27 out of 48 (56.3%) labels contained one or more efficacy claims based on COAs; of these, patient-reported outcomes were the most prevalent with claims identified in 19 labels (39.6%). CONCLUSION: There are ample opportunities for incorporating PED beyond COAs to inform drug development and facilitate availability of medicines tailored to patient needs. A higher level of transparency on the role of PED in regulatory decision-making and a clear path to PED-based label claims could incentivize sponsors and enable patient empowerment in treatment decisions.

Use of a Predictive Regression Model for Estimating Hold-Up Volume for Biologic Drug Product Presentations.

A drug delivery system is designed to administer a therapeutic dose according to its label claim. Upon delivery of a parenteral drug product, the volume remaining inside the container that cannot be extracted at the end of drug administration is called the hold-up volume (HUV) and is primarily considered product wastage. To meet the label claim, every drug product container is filled with a slight excess volume. For early-stage products in clinical phase, for which material availability is often a limitation, excess volume in drug product containers has to be determined experimentally using several grams of product. In such scenarios, established models that can predict HUV in primary drug product containers would be valuable for product development. The objective of this study was to determine HUV with 95% confidence intervals across various container closures and drug delivery systems by using aqueous PEG 400 solution mimicking the viscosity of biologic drug products. ISO 2R, 6R, and 10R vials and single-use hypodermic syringes attached to a Luer lock needle (25 gauge, 1½ in.) were used to mimic parenteral drug product container and delivery systems for determination of HUV. Glass prefilled syringes in 1 mL and 2.25 mL configurations were also used to determine HUV with 95% confidence intervals. A linear regression model was developed for determination of HUV as a function of viscosity and as a function of container closure and a needle-based delivery system. This model predicting HUV was confirmed by using monoclonal antibodies of varying formulations and viscosities for container closure and delivery systems tested in this study. The model provided here can be used to determine HUV for a particular container closure for a drug solution with known viscosity that can subsequently be used to evaluate fill volume specifications and label claim for a dosage form.

Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content.

STUDY OBJECTIVES: Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin. METHODS: A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin. Presence of serotonin was confirmed through analysis by ultraperformance liquid chromatography with mass spectrometry detection. RESULTS: Melatonin content was found to range from -83% to +478% of the labelled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin (5-hydroxytryptamine), a related indoleamine and controlled substance used in the treatment of several neurological disorders, was identified in eight of the supplements at levels of 1 to 75 µg. CONCLUSIONS: Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin. COMMENTARY: A commentary on this article appears in this issue on page 163.