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Multiple use applicator for vaginal tablets/vaginal inserts: compliance verification and suitability studies.

ABSTRACT: BACKGROUND:A newly developed multiple use applicator for vaginal tablets/vaginal inserts* was evaluated for its general suitability. There are no standard procedures described in guidelines or general accepted publications as to how this kind of product should be tested for suitability of purpose. METHODS:Due to the lack of existing standard procedures, three separate tests were designed and successful executed: (a) First, a patient acceptability evaluation was carried out as part of a phase III trial (registered in EudraCT on 9 Jan 2017, number 2017-000142-22 2. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number%3A2017-000142-22 ). (b) Secondly, a cleaning procedure for the applicator after simulated multiple use was developed and verified in order to prove a minimized risk of microbiological contamination of the device. A newly developed vaginal fluid to simulate multiple applications was applied for this trial. (c) Lastly, a third trial evaluated the mechanical stability and proper functionality of the applicator after multiple simulated uses. Even potential abrasion of material of the device was checked. RESULTS:Acceptable patient compliance of the new multiple use applicator was verified after 2 weeks of daily use. Furthermore, diary data assessments of patients participating in the Pharmacodynamic part of the trial were evaluated as well. Overall, patient acceptability of the new applicator was proven. The easy-to-use cleaning procedure for the applicator, which can even be carried out in a domestic environment, was developed and successfully verified for effectiveness, meeting all microbiological acceptance criteria for vaginal products of the European Pharmacopeia. The mechanical stability and proper functionality of the applicator after 50 simulated uses was also evaluated. All tested applicator batches (fresh and aged) passed the final evaluation, with no limitations in functionality. CONCLUSION:The tests developed and executed consider various compliance aspects of the newly developed applicator. Results of these individual tests met the expectations and/or the predefined acceptance criteria. All included trials performed produced results justifying and qualifying the applicator for the intended multiple-use. The procedures outlined may also be a guide as to how this kind of medical device can be tested for suitability. Trial registration Registered in EudraCT, number 2017-000142-22, start date 24 May 2017.

SUBMITTER: Brunner H

PROVIDER: S-EPMC7558499 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Multiple use applicator for vaginal tablets/vaginal inserts: compliance verification and suitability studies.

Brunner Heiko H Theodor Rudolf A RA

BMC women's health 20201015 1

<h4>Background</h4>A newly developed multiple use applicator for vaginal tablets/vaginal inserts* was evaluated for its general suitability. There are no standard procedures described in guidelines or general accepted publications as to how this kind of product should be tested for suitability of purpose.<h4>Methods</h4>Due to the lack of existing standard procedures, three separate tests were designed and successful executed: (a) First, a patient acceptability evaluation was carried out as part ...[more]

PMID: 33059630

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Project description:BackgroundOral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development.ObjectiveMTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design.Methods and findingsWe enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ?90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ?130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03).ConclusionsCompared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy.Trial registrationClinicalTrials.gov NCT00592124.

Project description:IntroductionE-cigarette studies have found that the use of a variety of flavors and customizable devices results in greater use frequency and user satisfaction. However, standardized research e-cigarettes are being developed as closed systems with limited flavor options, potentially limiting user satisfaction. In this study, we explore protocol compliance in an e-cigarette study using a standardized, assigned device with puff time and duration tracking (controlled e-cigarette) and potential limitations that controlled devices and e-liquids can introduce.MethodsIn a crossover study, 49 young adult e-cigarette users were recruited using convenience sampling and assigned a controlled e-cigarette device and flavored or unflavored e-liquids on standardized protocols. E-cigarette use frequency (number of puffs per day, collected from the device) and serum cotinine levels were obtained at each of three study visits over 3 weeks. The correlation of cotinine and e-cigarette use over the preceding week was calculated at each study visit.ResultsCorrelation of nicotine intake, as measured by serum cotinine, and puff time, as measured by puffs count and duration from the e-cigarette device, as an indicator of study protocol compliance, substantially declined after the first week of the study and were no longer correlated in the remaining study weeks (R2 = 0.53 and p ≤ .01 in week 1, R2 < 0.5 and p > .05 for remaining weeks).ConclusionsThere is an emerging need for controlled e-cigarette exposures studies, but low compliance in the use of assigned devices and e-liquids may be a limitation that needs to be mitigated in future studies.ImplicationsThis study is the first to analyze compliance with instructions to use a standardized e-cigarette device with puff time and duration tracking (controlled e-cigarette) across all subjects and an assigned e-liquid flavor over a 3-week period. We find that protocol compliance, as measured by correlations between e-cigarette use measures and cotinine levels, was only achieved in the first week of the study and declined thereafter. These findings indicate that the assignment of a study device and instruction to only use the study device with assigned e-liquid flavor may not be sufficient to ensure participant compliance with the study protocol. We suggest that additional measures, including behavioral and biological markers, are needed to ensure sole use of the study e-cigarette and e-liquid and to be able to interpret results from controlled e-cigarette studies.

Project description:To evaluate multiple applicator implant configurations of interstitial ultrasound devices for large volume ablation of liver tumors.A 3D bioacoustic-thermal model using the finite element method was implemented to assess multiple applicator implant configurations for thermal ablation with interstitial ultrasound energy. Interstitial applicators consist of linear arrays of up to four 10 mm-long tubular ultrasound transducers, each under separate and dynamic power control, enclosed within a water-cooled delivery catheter (2.4 mm OD). The authors considered parallel implants with two and three applicators (clustered configuration), spaced 2-3 cm apart, to simulate open surgical placement. In addition, the authors considered two applicator implants with applicators converging and diverging at angles of ∼20°, 30°, and 45° to simulate percutaneous placement. Heating experiments (10-15 min) were performed and compared against simulations employing the same experimental parameters. To estimate the performance of parallel, multiple applicator configurations in an in vivo setting, simulations were performed taking into account a range of blood perfusion levels (0, 5, 12, and 15 kg m(-3) s(-1)) that may occur in tumors of varying vascularity. The impact of tailoring the power supplied to individual transducer elements along the length of applicators is explored for applicators inserted in non-parallel (converging and diverging) configurations. Thermal dose (t(43) > 240 min) and temperature thresholds (T > 52 °C) were used to define the ablation zones, with dynamic changes to tissue acoustic and thermal properties incorporated within the model.Experiments in ex vivo bovine liver yielded ablation zones ranging between 4.0-5.6 cm × 3.2-4.9 cm, in cross section. Ablation zone dimensions predicted by simulations with similar parameters to the experiments were in close agreement (within 5 mm). Simulations of in vivo heating showed that 15 min heating and interapplicator spacing less than 3 cm are required to obtain contiguous, complete ablation zones. The ability to create complete ablation zone profiles for nonparallel implants was illustrated by tailoring applied power levels along the length of applicators.Parallel implants consisting of three interstitial ultrasound applicators in a triangular configuration yield complete ablation zones measuring up to 6.2 cm × 5.7 cm after 15 min heating. At larger interapplicator spacing, the level of blood perfusion in the tumor may yield indentations along the periphery of the ablation zone. Tailoring applied power along the length of the applicator can accommodate for nonparallel implants, without compromising safety.

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Multiple use applicator for vaginal tablets/vaginal inserts: compliance verification and suitability studies.

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Multiple use applicator for vaginal tablets/vaginal inserts: compliance verification and suitability studies.

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