The safety assessment of tampons: illustration of a comprehensive approach for four different products.

Introduction: We illustrate a comprehensive tampon safety assessment approach that assures products can be used safely. Material biocompatibility, vaginal mucosa assessment, vaginal microbiome evaluation, and in vitro assessment of potential risk of staphylococcal toxic shock syndrome expressed through growth of Staphylococcus aureus (S. aureus) and production of TSST-1 are the four essential portions of the approach. Post-marketing surveillance informs of possible health effects that warrant follow up. The approach meets or exceeds US and international regulatory guidance and is described through the example of four tampon products. Methods/Results: Each product is comprised mostly of large molecular weight components (cotton, rayon, polymers) that cannot pass the vaginal mucosa, are widely used across the industry, and replete with a vast body of safety data and a long history of safe use in the category. Quantitative risk assessment of all small molecular weight components assured a sufficient margin of safety supporting their use. Vaginal mucosa assessment confirmed that pressure points, rough edges and/or sharp contact points were absent. A randomized cross-over clinical trial (ClinicalTrials.gov Identifier: NCT03478371) revealed favorable comfort ratings, and few complaints of irritation, burning, stinging, or discomfort upon insertion, wear, and removal. Adverse events were few, mild in severity, self-limited and resolved without treatment. Vaginal microbiota assessment in vitro presented no adverse effect on microbial growth. Culture-independent microbiome analyses from vaginal swab samples obtained during the clinical trial showed no differences attributable to tampon usage, but instead due to statistically significant subject-to-subject variability. Growth of S. aureus and TSST-1 toxin production in the presence of any of the four products in vitro were statistically significantly reduced when compared to medium control alone. Discussion: The data from the four elements of the comprehensive safety assessment approach illustrated herein confirm that tampons evaluated using this system can be used safely for menstrual protection. A post-marketing surveillance system that monitors and responds to in-market experiences indicated in-use tolerability of the product among consumers, thus confirming the conclusions of the pre-marketing safety assessment.

Assessing the dermal compatibility of a new female incontinence product line.

CONTEXT: We have developed a line of products designed to better meet the overall needs of women suffering from urinary incontinence. The products are more discrete and contain a unique odor neutralizing technology (ONT). OBJECTIVE: This paper describes the overall skin compatibility program for this product line in which the new products were compared to negative controls and/or commercially marketed reference products with an established history of safe use. MATERIALS AND METHODS: Test products consisted of several product forms (light pads/pantiliners, moderate pads, briefs and taped diapers) with ONT and having various degrees of protection. Studies were conducted using standard protocols for 4-day and 21-day cumulative irritation, the Human Repeat Insult Patch Test (HRIPT), and the Behind-the-Knee (BTK) test for mechanical and chemical irritation. In one 4-day irritation study and one HRIPT, test subjects consisted of individuals with self-assessed sensitive skin. In addition, one 4-day study was conducted using normal skin sites, and sites compromised by tape stripping. Nonirritant controls were physiologic saline and/or current, commercially marketed incontinence products. All responses were evaluated by visual scoring of erythema. In addition, in the BTK, transepidermal water loss (TEWL) and adverse sensory effects collected from panelists' daily diaries were also evaluated. RESULTS AND DISCUSSION: Two 4-day cumulative irritation studies and one 21-day study demonstrated that a wide range of product forms (liners, light and moderate pads, briefs and adult diapers) produced skin reactions similar to the nonirritant controls. The 4-day study conducted using sensitive skin subjects showed good skin compatibility, and the test products were comparable to the nonirritant controls. In the 4-day study with both normal and compromised skin sites, test products produced mean erythema scores similar to the nonirritant controls. Three HRIPT separate studies confirm that the products do not induce contact sensitization, including one study conducted on individuals with self-assessed sensitive skin. In the BTK, test and control products produced similar irritation, as assessed by erythema, TEWL and sensory effects. CONCLUSION: The results from the patch tests and mechanical irritation test demonstrate good skin compatibility of the new line of products with the unique ONT. In addition, the forms of the product (i.e. liner, pad or brief), were equally compatible with skin.

Safety assessment of sanitary pads with a polymeric foam absorbent core.

Sanitary pads for menstrual hygiene have a layered design consisting of a fluid permeable surface (topsheet), an absorbent core, and an impermeable backing with adhesive. Most sanitary pads employ cellulose-based cores. This describes the safety evaluation of a menstrual pad with an emollient-treated topsheet and a novel polymeric foam core. A quantitative risk assessment was performed, which included: (1) toxicological evaluation of the raw material components; (2) quantitative exposure assessments of pad constituents, accounting for the fluid handling properties of the product and pertinent conditions of use; and (3) risk characterization for exposure to raw materials (e.g., potential for skin irritation, contact sensitization, or systemic effects, if relevant) and to the physical article itself (potential effects on skin friction, etc.). No significant risk of adverse effects was found. Five years of post-market surveillance substantiates that the product is well-tolerated (1 health complaint reported per 2 million products shipped to market) and surpasses women's expectations for menstrual protection and overall comfort and dryness. This report illustrates how the classical risk assessment paradigm, informed by the impact of product design, functionality and pertinent use conditions, allowed the systematic safety evaluation of a personal hygiene product with a novel, non-cellulosic absorbent foam core technology.

Clinical safety assessment of an ultra absorbency menstrual tampon.

BACKGROUND: Menstrual tampons are available in a range of absorbencies to allow women to use the product most appropriate to their needs. This study assessed the safety of an ultra absorbency (15 g to 18 g) tampon compared with a currently marketed super-plus absorbency (12 g to 15 g) tampon as a control. METHODS: Healthy women age 18-45 years (n = 95) were enrolled in this single-blind, crossover study. Subjects used, in random order, the experimental tampon during one menstrual cycle and the control tampon during the other. Subjects were also randomly assigned to receive either vaginal microbial assessments for determination of the presence and density of Staphylococcus aureus (n = 35) or colposcopic examinations for assessment of changes in the vaginal mucosa (n = 60). Data on comfort and acceptability of the tampons were collected by using diaries and questionnaires completed by the subjects in both groups. RESULTS: Twenty-eight women in the microbial assessment group and 43 in the colposcopic examination group completed the study; these subjects made up the primary analysis population. No differences in isolation frequency or cell density of S. aureus or in vaginal mucosal changes were observed with the experimental tampon in comparison with the control tampon. No reported adverse events were attributed to the experimental tampon. Both tampons received positive comfort ratings. CONCLUSIONS: Based upon microbial assessments, colposcopic examinations, adverse events, and subject reporting of comfort, the ultra absorbency tampon is similar in safety profile to the currently marketed super plus absorbency tampon.

Clinical safety-in-use study of a new tampon design.

OBJECTIVE: To confirm the safety of a new experimental Tampax tampon and applicator compared with that of a currently marketed Tampax tampon and applicator using comprehensive gynecological and microbiological assessments. METHODS: A 2-month, single-blind, randomized, crossover study was conducted in which each subject served as her own control. Safety was evaluated by comparing potential product-related irritation (using colposcopic examination and subject diary data), assessment of vaginal discharge, vaginal pH, and effects on selected microorganisms (yeast, Escherichia coli, Staphylococcus aureus and group B streptococci) obtained by vaginal swab cultures after normal menstrual use in the experimental and control groups. RESULTS: In total, 110 women completed the study. There were no significant differences between the groups that used either the experimental or control tampon with regard to prevalence or mean cell density for the selected microorganisms. No differences were observed in the incidence or severity of erythema, in abrasion or ulceration of the cervix, vagina, introitus, vulva or perineum, or in mean vaginal pH and discharge assessments. There were equivalent low incidences of reported symptoms such as discomfort during insertion, wear or removal, and a similar low incidence of burning, stinging or itching during use of either the control or experimental tampon. There was a more favorable overall product rating for the experimental tampon (p = 0.003). CONCLUSIONS: This approach provides a combination of gynecological, microbiological and self-reported (diary recall) methodologies in order to assess tampon safety during use more thoroughly than has previously been reported, and it supports a comparable safety profile for the experimental tampon and a currently marketed tampon.

Site-specific prevalence and cell densities of selected microbes in the lower reproductive tract of menstruating tampon users.

OBJECTIVE: To assess differences in prevalence and cell densities of enterococci, Gram negative enterics (GNEs), yeast and Staphylococcus aureus among four genital sites and to examine whether the presence of organisms at one site affected the presence of organisms at other sites. METHODS: Swab samples from the perineum, below and above the hymen, and the posterior fornix obtained from 52 tampon users on menstrual cycle day 3 were analyzed for site-specific prevalence and cell densities of microorganisms. RESULTS: Enterococci and GNEs were the most prevalent study organisms at all sites and decreased in prevalence from the perineum to the posterior fornix. Cell densities similarly decreased from below the hymen to the posterior fornix. Yeast were detected at the hymen only; S. aureus frequency was similarly low at all sites. Yeast and S. aureus site-specific cell densities were similar. The above- and below-hymen sites were similar in prevalence and cell density of organisms. An above-chance association existed between the presence of any study organism below the hymen and above the hymen and was strongest for GNEs. CONCLUSIONS: The pattern of genital colonization with enterococci and GNEs reflects their likely gastrointestinal source. The absence of significant differences in the prevalence and cell densities of study microflora above and below the hymen combined with an above-chance association of the presence of microorganisms at these regions suggests that the regions above and below the hymen are not different with respect to the presence of the organisms evaluated in this study.