Implications of laboratory tests of condom integrity.

BACKGROUND: There is sufficient evidence from Food and Drug Administration laboratory experiments and clinical studies to draw conclusions about the relative importance of holes and breakage to condoms. The laboratory test methods determined penetration of viruses or virus-size microspheres through holes in condoms under conditions that simulated or exaggerated those expected in actual use, and determined the frequency with which condoms might pass virus or microspheres and the amounts of passage in each case. GOALS: To summarize and comment on the significance of test results on latex, polyurethane, and natural membrane condoms as barriers to virus passage. STUDY DESIGN: Published and unpublished data addressing three distinct concerns were analyzed: (1) passage of virus or microspheres through small holes or pores inherent in the material of "intact" condoms which are undetectable by the standard water leak quality assurance test, (2) passage of virus or microspheres through larger holes in "leaker" condoms detectable by the water leak test but marketed because of the finite acceptable quality level (AQL) of the test, and (3) passage of virus through condoms that break during use. RESULTS: Extrapolating to the passage of semen expected during actual use allowed an analysis of the relative importance of breakage and water-leak-detectable or water-leak-undetectable holes. CONCLUSIONS: The relative importance of breaks and holes is related to the volume of semen that contains an "infectious dose" of a sexually transmitted disease (STD). When 0.1 mL to 1.0 mL exposures to semen are necessary for disease transmission, the risk during latex condom use primarily results not from holes, but from breakage of condoms. For smaller volumes of semen exposure (0.00001 mL and less), the presence of holes can be as important as breaks. The same qualitative argument pertains to a comparison of "leaker" condoms to the large majority of "intact" condoms.

PIP: This study examines the significance of test results on latex, polyurethane, and natural membrane condoms as barriers to virus passage. Data on three distinct concerns were analyzed: 1) passage of virus or microspheres through small holes or pores inherent in the material of "intact" condoms which are undetectable by the standard water leak quality assurance test; 2) passage of virus or microspheres through larger holes in "leaker" condoms detectable by the leak test but marketed because of the finite acceptable quality level of the test; and 3) passage of virus through condoms that break during use. The results showed that relative importance of breaks and holes is related to the volume of semen that contains an "infectious dose" of a sexually transmitted disease. When 0.1-1.0 ml exposures to semen are necessary for disease transmission, the risk during latex condom use primarily results not from holes but from breakage of condoms. For smaller volumes of semen exposure (0.00001 ml or less), the presence of holes can be as important as breaks. The same qualitative argument pertains to a comparison of "leaker" condoms to the large majority of "intact" condoms.

In vitro flow testing of glaucoma drainage devices.

OBJECTIVE: The study was intended to determine methods that could evaluate in vitro the flow characteristics of glaucoma drainage devices. DESIGN: Two test methods were used: (1) a gravity-driven flow test and (2) a syringe-pump-driven flow test. Eighteen devices, both valved and nonvalved, from 4 manufacturers were evaluated for their hydrodynamic resistance and the pressure at which the flow becomes 0. OUTCOME: Results show a wide variation in device performance, indicating a strong need for enhanced quality control procedures in the device manufacturing process. CONCLUSION: A gravity-driven flow test provides a reasonably quick test of both resistance and closing pressure, which might be useful as a manufacturing line test. The syringe-driven flow test requires more time but provides additional insight into device performance, and, therefore, might be useful as a design validation test.

U.S. Food and Drug Administration and regulation of medical devices in radiology.

The recent decision by the U.S. Food and Drug Administration (FDA) to approve one ultrasound imaging system for use in making breast biopsy decisions prompted considerable interest in the radiology community about the regulatory process and the associated implications for the practice of medicine. In this report, the concepts and statutory authority guiding the FDA in the regulation of medical devices are summarized and discussed, including the device classification scheme, premarket approval, premarket notification, and investigational device exemptions. Also, the critical concepts of safety and effectiveness for a given indication for use, the roles of advisory panels, and examples of imaging and interventional devices are described to shed light on the approval process.

Study of an acoustic technique to detect cavitation produced by a tilting disc valve.

BACKGROUND AND AIM OF THE STUDY: Transient cavitation has been directly observed near operating mechanical heart valves in vitro and inferred in vivo via the observation of pitting on explanted clinically used valves. Visual detection of cavitation bubbles, however, cannot be accomplished in vivo or when any opaque fluid, e.g. blood, is used. METHODS: This study examines a passive acoustic technique for detecting cavitation caused by a 27 mm tilting disc valve. We captured, valve closing sounds in vitro and attempted to detect a shift of energy into higher frequencies due to emission of broad-band noise caused by collapsing bubbles. The valve tester consists of a piston pump which directly drives the valve, a 16 cm diameter cylindrical lucite atrium and an air chamber in parallel to provide compliance. Water was used as a blood analog fluid. The cycle rate was altered to vary valve loading and produce cavitation. Acoustic signals were detected by a miniature hydrophone and a large area transducer and the waveforms were spectrum analyzed to 200 kHz and 500 kHz respectively. Cavitation onset was determined rising a high speed video camera. RESULTS: It was found that even under non-cavitating conditions, significant energy was produced at frequencies greater than 100 kHz, and this energy increased with increased load. The proportion of energy in high frequency bands, however, remained fairly constant when cavitation was not present and began to rise only after the cavitation threshold was reached. To isolate cavitation as an independent variable, data were taken with all system parameters constant, but using water under two different conditions. Degassed 17 degrees C water produced no visualizable bubbles, while aerated tap water at 43 degrees C showed a high degree of cavitation. CONCLUSIONS: The results indicate that cavitation, while causing a shift of energy to higher frequencies, is not the only mechanism responsible for the shift of energy into higher frequencies.

An interlaboratory comparison of the FDA protocol for the evaluation of cavitation potential of mechanical heart valves.

Five laboratories carried out measurements of cavitation threshold for a common set of six mechanical prosthetic heart valves, two each from three different manufacturers. This study was intended to evaluate to what extent FDA's current guidance for cavitation testing would lead to consistent results in a variety of laboratory settings and to seek areas for improvement in the recommended test protocol. The inter-laboratory study protocol specified: (1) characterization of the test fluid by oxygen content and electrical conductivity, (2) location and frequency response of pressure sensors, (3) determination of ventricular and atrial pressures (P) and loading rates (dP/dt) averaged over the time period of valve closure and over the time periods of 1 ms, 5 ms, and 20 ms prior to video visualization. The protocol did not specify: (1) the fluid pumping equipment to be used to generate cavitation, (2) the pump or fluid parameters adjusted to raise or lower the loading rate, (3) the equipment, technique, or sensitivity used to visualize cavitation, and (4) a specific definition of the threshold for cavitation. Results from the five laboratories are reported. Significant differences in results were observed in dP/dt and in the pressure difference across the valves during closure at cavitation threshold. Specific differences in test systems included a wide range of ventricular compliance and single valved versus double valved test systems. Three single valve systems with compliant ventricles produced results in reasonable agreement with one another. Further similarity in test equipment should be specified to assure adequate interlaboratory reliability for cavitation testing. Areas needing better specification include the design of the valve mount, the design of the cavitation generators, and qualitative criteria for detection of threshold cavitation.

A protocol for the evaluation of the cavitation potential of mechanical heart valves.

To assure the safety and effectiveness of prosthetic heart valves, the Food and Drug Administration requires performance testing prior to human use. Guidance for such testing is currently undergoing revision to include in vitro tests for cavitation potential. This work describes a test procedure to determine the minimum ventricular dp/dt associated with bubble formation. Cavitation bubbles as small as 0.5 mm diameter existing for 0.02 msec should be detectable by video imaging techniques.

Effectiveness of latex condoms as a barrier to human immunodeficiency virus-sized particles under conditions of simulated use.

Condoms were tested in an in vitro system simulating key physical conditions that can influence viral particle leakage through condoms during actual coitus. The system quantitatively addresses pressure, pH, temperature, surfactant properties, and anatomical geometry. A suspension of fluorescence-labeled, 110-nm polystyrene microspheres models free human immunodeficiency virus (HIV) in semen, and condom leakage is detected spectrofluorometrically. Leakage of HIV-sized particles through latex condoms was detectable (P less than 0.03) for as many as 29 of the 89 condoms tested. Worst-case condom barrier effectiveness (fluid transfer prevention), however, is shown to be at least 10(4) times better than not using a condom at all, suggesting that condom use substantially reduces but does not eliminate the risk of HIV transmission.

PIP: Physical science researchers tested the ability of 89 undamaged latex condoms manufactured in the US to prevent passage of HIV=size particles under simulated physiologic conditions at their Food and Drug Administration laboratory in Rockville, Maryland. The design of the test system considered particle size, pH, surface tension, and time. A suspension of polystyrene 110 nm microspheres labeled with fluorescent dye served as the HIV-sized particle model in semen. They challenged each condom with this suspension for 30 minutes. The test did not include motion since stretching over the penis accounts for most pore stretching. Leakage of fluorescent dye occurred in 29 condoms (p .03). 21 condoms leaked at minimum leak rates 1 nl/s, 7 at 1-6 nl/s, and 1 at around 10 nl/s. Assuming the leakage occurred through the only pore in each condom, the pore diameters ranged from 2 to 7 mcm. Also assuming an even more conservative criterion, the qualitative results were the same: 11 condoms with leak rates were nl/s vs. 6 condoms with leak rates 1-9 nl/s (p .002). The widely used 300 ml water test did not indicate any pores in any of the condoms. In the extreme and highly unlikely scenario of all the fluid being pumped out of the condom, the transfer rate would be about 0.1 mcl after 10 minutes of thrusting after ejaculation filled the condom with semen (i.e., 0.01% of a typical 3 ml ejaculate). Thus proper use of latex condoms would result in exposure reduction from HIV of at least 4 orders of magnitude. These findings demonstrated that use of latex condoms can significantly reduce the risk of HIV transmission, but it does not eliminate that risk.

Test method for evaluating the permeability of intact prophylactics to viral-size microspheres under simulated physiologic conditions.

The alarming number of AIDS cases has increased the attention given to barrier devices such as condoms. The authors describe a new test method that evaluates the permeability of the intact condom when subjected to simulated physiologic conditions. Fluorescent-labelled polystyrene microspheres (110 nm diameter) are used to model cell-free virus. Physical and chemical conditions that are present during coitus, such as pressure, pH, and temperature, are considered in the design of the method. The testing chamber is designed to be continuously monitored for changes in fluorescence due to leakage across the condom surface. The sensitivity of the system is 1 x 10(-5) of the original concentration of microsphere solution (3.4 x 10(11) particles/mL), which corresponds to leak rates as small as .001 microL/sec. The test provides an in vitro test of barrier material permeability relevant to actual use.

Digital acoustical analysis of normal and bimodal Björk-Shiley 60 degrees convexo-concave heart valves.

Fracture of the outlet strut of the Björk-Shiley 60 degrees convexo-concave (BS60CC) valve has been attributed to a bimodal closing pattern in certain valves in which the closing disk rotates about the inlet strut, causing upward displacement of the outlet strut and its eventual fracture. This article reports the in vivo studies of the normal BS60CC valve and the in vitro studies of the normal and bimodal BS60CC valves, using a digital acoustical signal processing technique, in which the individual collisions (impact history) of the occluder disk with the components of the valve body are revealed during each closing cycle. In vitro analysis of the closing acoustical signals of normal BS60CC valves showed impact history cluster width (IHCW) means of 2.07 +/- 0.85 ms (standard error), not significantly different from those of 1.86 +/- 0.58 ms (standard error) observed in 38 clinically normal patients with BS60CC valves (p greater than 0.1). The bimodal valves showed IHCW of 6.14 +/- 0.98 ms (standard error), in vitro, which was significantly greater than those observed in the normal in vitro valve group and in the normal patient population (p less than 0.0001).

The effects of a glycerin-based blood analog on the testing of bioprosthetic heart valves.

Detailed comparisons of aortic valvular flow using saline, with that using a glycerin-based blood analog in a pulse duplicator are reported. The experiments were carried out to determine whether exposure to glycerin caused stiffening of bioprosthetic valve leaflets. For two pericardial bioprostheses and for a mechanical valve we observed a fluid-dependent systolic volume flow, a fluid-dependent regurgitation volume, and fluid-dependent systolic pressure differences. Volume flow changes, both forward and reverse, are independent of valve type. The observed pressure differences, while proportional to fluid density for the mechanical valve, are fluid dependent in a more complicated way for the pericardial valves. However, no trend of changing valvular performance was observed over as much as 80 days of glycerin exposure, indicating that it is unlikely that the fluid-dependent performance was caused by glycerin absorption by the valve leaflets. We conclude that valid performance comparisons between mechanical and bioprosthetic valves may be made using a glycerin-based fluid. Furthermore, it appears that any detailed analysis of the physical mechanisms of valvular flow dissipation will require a properly matched blood analog.