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Latex rubber condoms: Predicting and extending shelf life
ELSEVIER
Latex Rubber Condoms: Predicting and Extending Shelf Life Michael J. Free,* Voraya Srisamang,* Donald E. Marlowe+
Janet Vail,* David Mercer,*
Condoms from five manufacturers were subjected to controlled exposuresof heat, humidity, and air and to different natural environments in five countries. Under aerobic conditions (condoms in permeable packages or unpackaged), stressproperties declined. The relationship between rate of decline as a function of temperature was quadratic. Under oxygen-restricted conditions (foil-wrapped packages) at average storage temperatures of 30°C and lower, strain properties declined with little or no significant change in stress properties. The effect is to cause condoms to become stiffer; high-breakage rates in use have been correlated with product stiffening. A new rationale for accelerated-aging tests to predict condom shelf stability is suggested, including a test to control the trend of condoms to stiffen. Silicone lubricant, impermeable packaging, and inclusion of antioxidants in the condom formulation can prevent or minimize aerobic breakdown of latex condoms. Specifying low-modulus condoms can prevent excessive stiffening. CONTRACEPTION 1996;53:221-229
latex condoms, latex stability, aging, shelf life, condom quality
KEY WORDS:
Introduction
I
n the spring of 1987, the United States Public Health Service began to advocate the use of condoms to assist in the prevention of the spread of the HIV virus. At that time, rigorous condomstability studies had not been required as part of purchasing specifications or regulatory requirements. Although the experience of the condom industry suggested that properly made, uniform products were stable for five years under proper storage conditions, *Program for Appropriate Technology in Health (PATH), 4 Nickerson Street, Seattle, WA 98109; TUS Food and Drug Administration (USFDA), 9200 Corporate Boulevard (HFZ 542) Room OlOD, Rockville, MD 20850; *US Food and Drug Administration (USFDA), Center for Devices and Radiological Health, Office of Science and Technology, 9200 Corporate Boulevard (HFZ 100) Rockville, MD 20850 Name and address for correspondence: Janet Vail, Program for Appropriate Technology and Health, 4 Nickerson Street, Seattle, WA 98109. Tel: 206-285. 3500; Fax: 206-285-6619 Submitted for publication March 13, 1995 Revised November 30, 1995 Accepted for publication January 19, 1996
0 1996 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
Richard
Kotz,t and
very little in the way of stability data was publicly accessible. In the few prior studies of extreme environmentsl (such as those of tropical countries or under conditions of suboptimal storage), severe changes in condom mechanical properties had been observed as early as 1 i/2 to 2% years from the date of manufacture. This was less than half the conventional five-year shelf life. No data are available in the literature that describes the long-term aging characteristics of condoms of different formulations and the effect of different packaging and lubricants. An informal group representing government, users, and condom manufacturers proposed a study of the changes in mechanical properties that occur when condoms are exposed for several years to the natural environment or to controlled environments at different temperatures. The US Food and Drug Administration (FDA) funded such research beginning in October 1988. PATH has been the principal investigator for the study under contract to the Washington State Board of Pharmacy (WSBP). Supplementary studies were supported by Family Health International (FHI) with funds from the United States Agency for International Development (USAID). The research had three main components: (1) factors affecting natural rubber latex condoms during storage under controlled conditions, (2) changes in natural rubber latex condoms stored in different natural environments, and (3) investigation of the predictive value of accelerated aging at elevated temperatures. The studies were carried out between October 1988 and July 1995. This paper describes the principal findings and discusses their practical significance in light of published condom-breakage studies, current standards, and procurement specifications designed for supply of condoms to developing countries.
Materials
and Methods
Condoms representing a variety of formulations and production processes manufactured between June and December 1989 were purchased from four US manufacturers under the aegis of the Health Industry ISSN OOIO-7824/96/$15.00 PI\ SOOIO-7624(96)COO41-8
222
Manufacturers Association (HIMA). In addition, condoms produced by five US manufacturers (three of which were the same as the original four manufacturers) were purchased from distributors/wholesalers by the Washington State Board of Pharmacy; these were manufactured between September 1993 and February 1994. Finally, one study was carried out with condoms supplied by two of the original four manufacturers; these condoms were produced in April and August 1992. All condom samples complied with prevailing ASTM D 3492 [American Society for Testing and Materials, Standard Specification for Rubber Contraceptives (Condoms)] and IS0 4074 Part 6 (International Organization for Standardization, Rubber CondomsPart 6: Determination of Bursting Volume and Pressure) standards. Treatments included: l
l
Storage under typical local conditions in Bangladesh, Mexico, Pakistan, Thailand, and the United States (four sites in Washington state). Storage in temperature-controlled chambers at 20”, 30”, 45”, and 70°C.
In addition to five manufacturers (types), other variables applied to one or more types were l
l
Type of lubricant (powder only, silicone, silicone with nonoxynol-9, water-soluble lubricant, watersoluble lubricant with nonoxynol-9). Type of package (no package, all-plastic package, and plastic and aluminum-foil laminates).
Whether packaged or unpackaged, all condoms were exposed in the normal rolled configuration. Tests for mechanical properties carried out at intervals throughout the storage period were l l l l l
Contraception 1996;53:221-229
Free et al.
Air-inflation test Tensile tests Vacuum test for package integrity Gas analysis using gas chromatography Environmental temperature and humidity monitoring at storage sites using a memory data logger (Grant Model MQ 8-2U/2L/AD).
Automated condom airburst equipment, customized software, and data-handling systems were developed for this study, permitting a high volume of accurate testing. The system was validated and periodically checked against the results of up to six independent laboratories through an interlaboratory calibration network designed to minimize variability. Statistical Methods For field studies, the statistical comparison of various types of condoms on the four key properties (burst
pressure, burst volume, break force, and elongation) were based on fitting linear models using the maximum likelihood method. These models included dummy variables for the type of condoms, whether or not the site was a local or foreign and a nested site specific random effect. The random effect was assumed to be normally distributed with mean zero. All comparisons were made by first constructing appropriate contrasts and by comparing the mean squares attributable to these contrasts to the appropriate mean square errors through F-statistics. Due to the nested nature of the random effects, the appropriate mean square errors were determined by calculating the expected mean squares. The residual plots and other diagnostic tools were used to identify departures from the assumptions. To determine the relationship between aging and temperature in accelerated-aging tests, mean values at each time period for airburst parameters (pressure and volume), force and elongation were computed for each combination of condom formulation, lubrication, and packaging at each temperature. These values were then plotted to determine if they conformed to a general log-linear curve. In the accelerated-aging data, only the mean pressure values approximated this curve. The rate of change in these parameters as a function of time and temperature was estimated by regressing the log of the proportion of the mean burst pressure value to the mean baseline value (taken as the first mean in the time series). Under an assumption of first-order degradation at each temperature, the logs of the proportions would be linear. A leastsquares fit of these logs was calculated to estimate a constant rate of change per unit of time (expressed as the coefficient, fit at each temperature, t, in the equation ln(M,/Mo), = &*Timei, where Mi is the mean parameter of interest at Time, and Ma is the mean parameter at baseline). These rates, &, were then fit using least squares regression to obtain quadratic functions describing the curve in the change in degradation rates related to temperature. All analyses were done using the SPSS statistical package.
Results At average storage temperatures of 30°C or lower, two distinct trends were evident in the mechanical properties of natural rubber latex condoms. One of these trends appeared independent of the presence of airoccurring under oxygen-restricted (foil-wrapped) conditions. The other occurred only under aerobic conditions. The changes that were observed under oxygenrestricted conditions (Figure 1) were characterized by
Contraception 1996;53:221-229
Condom Shelf Life
Burst Volume
T
223
Elongation
+stdev
95n
wo
850
800
18 750 14 -
s
Elongation
pD
700 0
months
I2
24
36
48
60
Burst Pressure
0
72
Break Force
2.4
120
2.0
loo
1.6
a0
1.2
60 E D t
b 0.8
40 0
months
12
24
36
48
60
n
Figure 1. Changes in mechanical properties of foilwrapped natural rubber condoms during storage. Condoms from one manufacturer der climate-controlled relative humidity).
and production lot were stored unstorage (23°C + 5°C and 40°C * 5%
a significant (p < 0.0001) decline in strain properties (burst volume and tensile elongation-at-break) with no or little significant change in stress properties (tensile force-at-break and burst pressure). The rate of change diminished over time, stabilizing at a level that was dependent upon the mean storage temperature (Figure 2). These changes appeared to be related to heat exposure [Figure 3). The net effect of this trend is to cause the condoms to become stiffer (increased elastic modulus) during storage, a change that is further enhanced in hot climates (Figure 4). The maximum degree of stiffness reached depends primarily upon the initial elasticity of the condom-a consequence of the latex formulation and manufacturing process. When condoms were exposed to air (as in permeable plastic packages), a similar trend was observed during the first two years but was subsequently offset by aerobic degradation (Figure 4). Since changes in stress properties were relatively
months
I2
24
36
48
60
72
Figure 2. Changes in foil-wrapped natural rubber condoms stored in different climates. The indicated temperatures represent the average temperature at each warehouse over the entire storage period. All condoms were from the same manufacturer and production lot.
small or subject to other environmental influences, strain properties, particularly burst volume appeared to be the most useful parameter to assess and monitor the stiffness of natural rubber latex condoms. In these studies, initial mean burst volume of the four types ranged from 27 liters to 55 liters (inflation length 150 mm, width 52 to 54 mm). Under aerobic conditions, other trends were evident. Aerobic conditions included unpackaged condoms and condoms packaged in oxygen-permeable plastic film. Oxygen permeability of the commercial condom packages made of plastic film differed significantly (p < 0.0001) from packages containing aluminum foil (Figure 5). The rate of decline of burst pressure was significantly higher, and the shelf life Mean Burst Volume R2 = 0.450 I
28 I-
..
Figure 3. Relation between air burst volume and heat exposure of natural rubber condoms during storage. Condoms from one manufacturer and production lot were stored in sites in tropical and temperate climates.
224
Contraception 1996;53:221-229
Free et al.
2.7
I
Burst Pressure 2.5
600% Modulus 7
+ st dev
0 0 2.4
0
O
Foil Packaged __o- ---6 ___----
-
h
.
2.0
d---b 1.5
10
0.5
4
1.7 /]
0.0
0
months
12
24
36
48
60
0
72
4. Change in Young’s elastic modulus for natural rubber condoms during storage in tropical environments. Condoms from the same manufacturer and production lot packagedin aluminum foil and plastic were stored in warehouses in Pakistan and Thailand (average temperature:
months
3
6
9
12
3
6
9
12
Figure
26”C-
28°C).
significantly shorter at 45°C for plastic-packaged condoms (12 to 18 months) compared with condoms from the same production lot packaged in foil-containing materials (30 months). When unpackaged condoms of all types were stored at temperatures of 30” and 45”C, changes in airburst properties (both volume and pressure) were sufficiently high to render the condoms unfit for use within a three- to six-month period. However, no significant change could be detected in the tensile properties (Figure 6). Localized discoloration and cracking of the extreme end of the condoms could be visualized (Figure 7). This affected area lay outside the tight roll of the condom. The tensile specimens are always Burst Pressure 2.5 16.5%
Foil Package
02
I
2.0
I.
‘:‘%02
1.6%
O2
1.6%
0,
1.5
0.5 B 0.0
I
1 -stdcv
4 0
months
6
12
18
24
30
5. Effect of packaging material on aging of natural rubber condoms. Condoms from the same manufacturer and production lot were packaged in all-plastic or plastic/ aluminum-foil laminate and stored in an environmental chamber at 45”C+2’C. Oxygen levels inside the packages were assessedusing gas chromatography. Figure
Break Force 85
75
65
55
1
45
i 0
months
6. Changesin natural rubber condoms exposed to air at 45°C. Condoms from two manufacturers were removed from their packages(not unrolled) and stored in an oven at 4S’C*2’C. Figure
cut from midway along the length of the condoms, well inside the rolled portion. This result suggests that the condoms were unevenly affected under these conditions. These localized changes were not evident at lower (20°C) or higher (70°C) temperatures. Silicone lubricant appeared to provide significant (p < 0.00001) protection against this localized deterioration at 30°C (Figure 8). At the temperature used for accelerated aging (7O”C), the intrinsic ability of unpackaged condoms to resist aerobic deterioration varied widely among types of condoms, indicating that some formulations relied more heavily than others upon their packaging to achieve acceptable shelf life. High humidity (above 65%RH) significantly (p < 0.00001) increased the rate of decline of burst pressure in unpackaged condoms at 70°C. Four different formulations of unpackaged (lubricated and unlubricated) condoms-aged artificially at 20, 30, 45, and 70”C-provided the basis for an analysis of the kinetics of aerobic changes in condoms during storage. Storage times ranged from 100 days at
Condom
Contraception 1996:53:221-229
Shelf Life
225
Mean Burst Volume Silicone
Lubricated
I
OJ 0
months
IO
20
30
40
Mean Burst Pressure 2.2 , t
Figure 7. Typical localized discoloration and cracking of a natural rubber condom after exposure to air at 45°C for six months. The dotted lines show the part of the condom taken for the tensile specimen. A special cutting die was developed to eliminate any edgeirregularities.
70°C to more than five years at 20°C. Of all the parameters measured (tensile and air inflation), stress parameters-most notably burst pressure-exhibited the most consistent pattern of decline over time (from 42 months at 20” and 3O”C, to 100 days at 70°C). Strain parameters under aerobic conditions were characterized by a biphasic change, increasing initially and then declining. Consequently, burst pressure was selected as the most sensitive indicator of aerobic deterioration. The rate of change (expressed as Aln Pi/PO) as a function of temperature for four condom formulations are equation, shown in Figure 9. In a formal Arrhenius this temperature-dependent rate of change is assumed analyses of the conto be constant. In our empirical
dom data, it is shown that the change in the rate of decline of burst pressure associated with temperature is quadratic and greatest at high temperatures. This quadratic function can then be used to predict degradation rates at ambient temperatures (e.g., 20°C) from
accelerated rates observed at high temperatures (e.g., 70°C). These data suggest that the reactions involved are consistent across formulations. Based upon the mean curve for these four formulations and, assuming
Sihme
I
Lubricated
1.0 $ I 0
months
IO
20
30
40
Figure 8. The effect of silicone-basedlubricant on changes in natural rubber condomsexposedto air at 30°C. Condoms from one manufacturer and dipping lot-with and without lubricant-were removed from their packagesand stored in an oven at 30°C * 1°C.
(arbitrarily) a maximum acceptable decline in burst pressure of 30 percent, the shelf life of unpackaged natural rubber latex condoms is estimated to be in the order of: six years at 2O”C, three years at 3O”C, seven weeks at 45”C, and twelve days at 70°C. The impact of impermeable, hermetically-sealed packaging on average shelf life was to increase shelf life well beyond five years at environmental temperatures. Current accelerated-aging tests for predicting shelf stability of condoms use exposure times ranging from two to seven days at 7O”C, with or without change in the minimum allowable tensile air-inflation limits. These protocols were based upon kinetic studies’ performed on 2-mm-thick natural rubber latex samples. Apparently, the first-order changes in elongation-atbreak demonstrated in that study do not apply to formed product with a wall thickness of less than 0.08 mm. The current study and recent human-use studies,3-5 suggest a new rationale for accelerated-aging studies as they apply to condoms. An aging temperature of 70°C remains meaningful. However, changes
226
Free et al.
Contraception 1996;53:221-229
Rate of Change in Burst Pmsure 0
20
Teqerature(oc)
40
60
Figure 9. Relationship between temperature and aging for natural rubber condoms from four manufacturers. The dotted line represents the mean of the four brands. The effect of impermeable packaging on this relationship is shown for one of the brands.
in inflation parameters of some formulations during the first two days of incubation at 70°C are not typical of subsequent changes (Figure 10). The test can be made more universally applicable by disregarding change in the first two days of accelerated aging. An aging period of ten days is proposed, with half the sample drawn at two days and the remainder at ten days. Since eight days at 70°C has been shown in this present study to typically reduce mean burst pressure by 20 percent, the test for an acceptable level of aerobic deterioration can be: Mean Burst Pressure,, days
Packaged
Mean Burst Pressure 2.5
1
1.0 %”
i
2 0.80 Mean Burst Pressure, dayS
A second test of the trend of condoms to become stiff at elevated storage temperatures can be applied using the volume data derived from the same test. Recent human-use studies’ with condoms of similar formulation to one of those used in this current aging study demonstrated a significant effect of stiffening on breakage during use. These data-although based upon samples of several different lots, storage sites, and ages-show a trend in burst volume over time that is similar to that seen with the comparable condoms in the current prospective controlled study (Figure 111, while burst pressure remained relatively stable in both studies. This relationship between decrease in strain properties (while stress properties remain constant) and breakage during use (Figure 12) suggests the need for a minimum batch average volume after (accelerated) aging, providing that stress properties are not unduly compromised. The data in
0.5 3
0
.
zdays
5
days
1
15
20
I.5
20
Unpackaged
Mean Burst Pressure 2.5
10
i
0.0
O 2days
5
w
10
10. Change in air burst pressureof natural rubber condoms at 70°C. Condoms from two manufacturers were stored in an oven at 70”*2’C.
Figure
Contraception i996;53:221-229
Condom Shelf Life
previously. Thus, the test for allowable stiffening after accelerated aging would Burst Volume 3 30 liters. This limit might be decreased slightly condoms (i.e., proportional to width) and dently be increased for condoms purchased and use in hot climates.
Mean Burst Volume
l
*
l
227
maximum be Mean for smaller might prufor storage
Discussion , 0
months
24
I2
36
48
60
72
84
Figure 11. Comparison of changes in burst volume of natural rubber condoms from the current study and from a recent human-use study (Steiner, Foldesy, Cole, Carter. Study to determine the correlation between condom breakagein human-use and laboratory test results. Contraception 46:279-88;1992). Condoms from a single production lot were stored in warehouses in Pakistan, Thailand, and Mexico and sampled at intervals. In the human-use study, condoms from different lots were sampledfrom several developing-world sites.
Figure 12 do not indicate
where this threshold should be set, but suggest that batch mean burst volumes of 30 liters or above are preferable. Keeping in mind that changes in modulus are most likely due to continued vulcanization, which occurs to a lesser extent after ten days at 70°C than at environmental temperatures, a minimum limit of 30 liters is proposed for burst volume following the 70°C aging protocol outlined BreakageRate 20
R2 = 0.80
1
IS -I
IO
-
5 *I
count in assessing new products. Since stress proper-
04
IS
The results of this study demonstrate that natural rubber latex condoms can be stable over many yearseven in hot and humid climates-if they are properly formulated, manufactured, and packaged. The challenge for the institutional and public purchasers or regulators is how to qualify products before purchase or distribution to be sure that they will be fit for use at any time and after any likely circumstances of shipping and storage. The current study offers some clues of what to look for in freshly manufactured products that might affect their stability and effectiveness. It also offers a new rationale for predictive shelf life testing by accelerated aging at 70°C. In addition, it provides a basis by which to analyze apparent problems with condoms that have been in storage. Current standards provide good control over leakage, and this remains an important qualifier of the product and of the manufacturing practices used to produce it. However, breakage rates are generally higher than leakage rates, and each incidence of breakage results in a higher risk of infection or pregnancy than does the presence of a microscopic hole. Since-unlike holes-breakage potential cannot be measured directly, mechanical properties like air inflation or tensile are used as surrogates. As more is learned about the stress and strain properties and their relation with breakage during use, it is important to modify standards, specifications, and buying practices to take advantage of that new knowledge. From the current aging study and human-use studies, it has become apparent that the elastic modulus (or stiffness) of the latex film must be taken into ac-
20
liters mean burst
25
30
35
volume
Figure 12. Relation between air burst volume of natural rubber condoms and breakage during use. Condoms are essentially equivalent to manufacturer 1 in the present study but represent multiple lots stored in several overseassites. Adapted from Steiner, Foldesy, Cole, Carter. Study to determine the correlation between condom breakage in human-useand laboratory test results. Contraception 46:27988;1992.
ties (measured as burst pressure or force-at-break) change very little in well protected condoms, these strain properties-particularly burst volume-are good surrogates for elastic modulus. From the most recent human-use study,5 it appears that when strain properties fall below a certain level, breakage during use increases dramatically (see Figure 12). The current study shows that burst volume of protected condoms declines in the first one to three years of storage, eventually stabilizing at a level that is inversely related to storage temperature. In view of these findings, buyers should qualify new condoms in relation-
228
Change
Free et al.
(%)
Contraception 1996;53:221-229
Shelf Vulcanization
Change
(%)
Localized Degradation (Aerobic)
Pressure Fame
n
Change (40)
General Degradation (Aerobic)
Figure 13. Patterns of change in ultimate stressand strain properties of natural rubber condoms under different aging conditions. (A) At environmental temperatures (data shown is from 20°C storage),a decline in strain properties with little or no changein stressproperties occurs under anaerobic conditions and in condomsexposedto air but resistant to oxidation. This pattern of change is consistent with the continuing formation of sulfur-sulfur crosslinks (vulcanization) and lead to an increasein elastic modulus (stiffness). (B) At high environmental temperatures (3045”C), a rapid decline in air-inflation properties occurs in the rolled condom exposedto air through broken or highly-permeable packages.Tensile properties are unaffected becausethe section of the condom used for this test is protected by the many layers of latex film in the rolled portion. Apparently, the rate of oxygen uptake at the exposedsurface exceedsthe rate of diffusion through the latex film at the temperatures. (C) Stress properties of rolled condoms exposedto air at any temperature through broken or permeable packagesdecline steadily and provide the best means to monitor oxidative changesin stored condoms. At higher temperatures or in condomswith a low resistanceto oxidation, strain properties may initially increasebefore eventually decreasing (data shown are from 70°C storage). ship to a minimum mean or median burst volume, according to a protocol such as the one proposed here. The changes in modulus discussed above represent postproduction curing of the latex film rather than actual degradation. By contrast, the aerobic breakdown of the latex film is true degradation. However, there are several effective means to prevent or minimize this type of change. These include antioxidant, silicone lubricant, and impermeable (usually containing aluminum foil) packaging. Since the protective effect of these is additive, there is no reason why properly formulated, cured, and packaged condoms cannot
be made to last five years or longer-even
in tropical
and other harsh environments. Qualification of newly manufactured products include specifying aluminum-foil laminates as packaging materials, checking for intact package seals, and specifying silicone lubricant. A test for resistance to oxidation has been proposed based upon aerobic kinetics of four brands of US-manufactured condoms. Buyers for tropical and other harsh environments can augment the proposed test by including condoms removed from their packages. Using this augmented test-comparing results from unpackaged and packaged condoms-an assessment can be made of the package dependency of the product. It seems prudent for these challenging con-
Contraception 1996;53:221-229
Condom Shelf Life
ditions to purchase condoms that will stay in good condition even if the package is compromised. Problems have occurred with stored condoms due to actual changes in properties or perceived poor performance. In many cases, these have been hard to assess. Many of these cases have involved discoloration, odor, or package changes that negatively affect user acceptability. In some cases, these have been a consequence of excess stiffening or of aerobic degradation. Based upon the present study, a “thumbprint” of the product can be used to analyze the type of changes that may have taken place assuming that the test data on samples of aged product can be compared with data obtained when the condoms were new (or from contemporary new product of the same make). Figure 13 illustrates the changes in air-inflation and tensile parameters when different aging factors predominate. A fall in strain parameters (with little or no change in stress parameters] suggests that the condoms are well protected from aerobic degradation but have undergone shelf vulcanization-resulting in a stiffer condom. A pronounced fall in air-inflation parameters (with little or no change in tensile parameters) suggests localized deterioration, high-temperature exposure, and poor packaging. A fall in stress parameters (with less or no fall in early strain parameters) suggests a lack of intrinsic (antioxidant) protection and oxygen-permeable packaging. In most cases, more than one of these factors may be operating at the same time so that the picture may not be as clear. However, all of these “thumbprints” have been observed by the authors in tests of aged condoms over the past 20 years.
Acknowledgments This research was supported Food and Drug Administration
by the United States by contract with the
229
Washington State Board of Pharmacy. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. Partial support for this study (package type at 45°C) was provided by Family Health International (FHI) with funds from the United States Agency for International Development (USAID), although the views expressed in this article do not necessarily reflect those of FHI or USAID. The constant diligence of PATH laboratory staff was critical to conducting the research. Thanks go to the National Research Institute of Fertility Control, Karachi, Pakistan; Gonoshasthaya Pharmaceuticals, Limited, Dhaka, Bangladesh; Northwestern Drug Company of Auburn, Washington; and the City of Seattle Public Health Department for serving as study sites.
References 1. Belsky RL. An assessment of reported condom deterioration in Bangladesh. A report supported by United States Agency for International Development (AIDS) AID/DSPE-C-0053, 1982. 2. Mandel J, Roth FL, Steel MN, Stiehler RD. Measurement of the aging of rubber vulcanizates. J Res Nat1 Bureau Std 1959;63C:141-5. 3. Free MJ, Skiens EW, Morrow MM. Relationship between condom strength and failure during use. Contraception 1980;22:31-7. 4. Free MJ, Hutchings J, Firman L, et al. An assessment of burst strength distribution data for monitoring quality of condom stocks in developing countries. Contraception 1986;33:285-99. 5. Steiner M, Foldesy R, Cole D, Carter E. Study to determine the correlation between condom breakage in human use and laboratory test results. Contraception 1992; 46:279-88.
Latex Rubber Condoms: Predicting and Extending Shelf Life Michael J. Free,* Voraya Srisamang,* Donald E. Marlowe+
Janet Vail,* David Mercer,*
Condoms from five manufacturers were subjected to controlled exposuresof heat, humidity, and air and to different natural environments in five countries. Under aerobic conditions (condoms in permeable packages or unpackaged), stressproperties declined. The relationship between rate of decline as a function of temperature was quadratic. Under oxygen-restricted conditions (foil-wrapped packages) at average storage temperatures of 30°C and lower, strain properties declined with little or no significant change in stress properties. The effect is to cause condoms to become stiffer; high-breakage rates in use have been correlated with product stiffening. A new rationale for accelerated-aging tests to predict condom shelf stability is suggested, including a test to control the trend of condoms to stiffen. Silicone lubricant, impermeable packaging, and inclusion of antioxidants in the condom formulation can prevent or minimize aerobic breakdown of latex condoms. Specifying low-modulus condoms can prevent excessive stiffening. CONTRACEPTION 1996;53:221-229
latex condoms, latex stability, aging, shelf life, condom quality
KEY WORDS:
Introduction
I
n the spring of 1987, the United States Public Health Service began to advocate the use of condoms to assist in the prevention of the spread of the HIV virus. At that time, rigorous condomstability studies had not been required as part of purchasing specifications or regulatory requirements. Although the experience of the condom industry suggested that properly made, uniform products were stable for five years under proper storage conditions, *Program for Appropriate Technology in Health (PATH), 4 Nickerson Street, Seattle, WA 98109; TUS Food and Drug Administration (USFDA), 9200 Corporate Boulevard (HFZ 542) Room OlOD, Rockville, MD 20850; *US Food and Drug Administration (USFDA), Center for Devices and Radiological Health, Office of Science and Technology, 9200 Corporate Boulevard (HFZ 100) Rockville, MD 20850 Name and address for correspondence: Janet Vail, Program for Appropriate Technology and Health, 4 Nickerson Street, Seattle, WA 98109. Tel: 206-285. 3500; Fax: 206-285-6619 Submitted for publication March 13, 1995 Revised November 30, 1995 Accepted for publication January 19, 1996
0 1996 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010
Richard
Kotz,t and
very little in the way of stability data was publicly accessible. In the few prior studies of extreme environmentsl (such as those of tropical countries or under conditions of suboptimal storage), severe changes in condom mechanical properties had been observed as early as 1 i/2 to 2% years from the date of manufacture. This was less than half the conventional five-year shelf life. No data are available in the literature that describes the long-term aging characteristics of condoms of different formulations and the effect of different packaging and lubricants. An informal group representing government, users, and condom manufacturers proposed a study of the changes in mechanical properties that occur when condoms are exposed for several years to the natural environment or to controlled environments at different temperatures. The US Food and Drug Administration (FDA) funded such research beginning in October 1988. PATH has been the principal investigator for the study under contract to the Washington State Board of Pharmacy (WSBP). Supplementary studies were supported by Family Health International (FHI) with funds from the United States Agency for International Development (USAID). The research had three main components: (1) factors affecting natural rubber latex condoms during storage under controlled conditions, (2) changes in natural rubber latex condoms stored in different natural environments, and (3) investigation of the predictive value of accelerated aging at elevated temperatures. The studies were carried out between October 1988 and July 1995. This paper describes the principal findings and discusses their practical significance in light of published condom-breakage studies, current standards, and procurement specifications designed for supply of condoms to developing countries.
Materials
and Methods
Condoms representing a variety of formulations and production processes manufactured between June and December 1989 were purchased from four US manufacturers under the aegis of the Health Industry ISSN OOIO-7824/96/$15.00 PI\ SOOIO-7624(96)COO41-8
222
Manufacturers Association (HIMA). In addition, condoms produced by five US manufacturers (three of which were the same as the original four manufacturers) were purchased from distributors/wholesalers by the Washington State Board of Pharmacy; these were manufactured between September 1993 and February 1994. Finally, one study was carried out with condoms supplied by two of the original four manufacturers; these condoms were produced in April and August 1992. All condom samples complied with prevailing ASTM D 3492 [American Society for Testing and Materials, Standard Specification for Rubber Contraceptives (Condoms)] and IS0 4074 Part 6 (International Organization for Standardization, Rubber CondomsPart 6: Determination of Bursting Volume and Pressure) standards. Treatments included: l
l
Storage under typical local conditions in Bangladesh, Mexico, Pakistan, Thailand, and the United States (four sites in Washington state). Storage in temperature-controlled chambers at 20”, 30”, 45”, and 70°C.
In addition to five manufacturers (types), other variables applied to one or more types were l
l
Type of lubricant (powder only, silicone, silicone with nonoxynol-9, water-soluble lubricant, watersoluble lubricant with nonoxynol-9). Type of package (no package, all-plastic package, and plastic and aluminum-foil laminates).
Whether packaged or unpackaged, all condoms were exposed in the normal rolled configuration. Tests for mechanical properties carried out at intervals throughout the storage period were l l l l l
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Free et al.
Air-inflation test Tensile tests Vacuum test for package integrity Gas analysis using gas chromatography Environmental temperature and humidity monitoring at storage sites using a memory data logger (Grant Model MQ 8-2U/2L/AD).
Automated condom airburst equipment, customized software, and data-handling systems were developed for this study, permitting a high volume of accurate testing. The system was validated and periodically checked against the results of up to six independent laboratories through an interlaboratory calibration network designed to minimize variability. Statistical Methods For field studies, the statistical comparison of various types of condoms on the four key properties (burst
pressure, burst volume, break force, and elongation) were based on fitting linear models using the maximum likelihood method. These models included dummy variables for the type of condoms, whether or not the site was a local or foreign and a nested site specific random effect. The random effect was assumed to be normally distributed with mean zero. All comparisons were made by first constructing appropriate contrasts and by comparing the mean squares attributable to these contrasts to the appropriate mean square errors through F-statistics. Due to the nested nature of the random effects, the appropriate mean square errors were determined by calculating the expected mean squares. The residual plots and other diagnostic tools were used to identify departures from the assumptions. To determine the relationship between aging and temperature in accelerated-aging tests, mean values at each time period for airburst parameters (pressure and volume), force and elongation were computed for each combination of condom formulation, lubrication, and packaging at each temperature. These values were then plotted to determine if they conformed to a general log-linear curve. In the accelerated-aging data, only the mean pressure values approximated this curve. The rate of change in these parameters as a function of time and temperature was estimated by regressing the log of the proportion of the mean burst pressure value to the mean baseline value (taken as the first mean in the time series). Under an assumption of first-order degradation at each temperature, the logs of the proportions would be linear. A leastsquares fit of these logs was calculated to estimate a constant rate of change per unit of time (expressed as the coefficient, fit at each temperature, t, in the equation ln(M,/Mo), = &*Timei, where Mi is the mean parameter of interest at Time, and Ma is the mean parameter at baseline). These rates, &, were then fit using least squares regression to obtain quadratic functions describing the curve in the change in degradation rates related to temperature. All analyses were done using the SPSS statistical package.
Results At average storage temperatures of 30°C or lower, two distinct trends were evident in the mechanical properties of natural rubber latex condoms. One of these trends appeared independent of the presence of airoccurring under oxygen-restricted (foil-wrapped) conditions. The other occurred only under aerobic conditions. The changes that were observed under oxygenrestricted conditions (Figure 1) were characterized by
Contraception 1996;53:221-229
Condom Shelf Life
Burst Volume
T
223
Elongation
+stdev
95n
wo
850
800
18 750 14 -
s
Elongation
pD
700 0
months
I2
24
36
48
60
Burst Pressure
0
72
Break Force
2.4
120
2.0
loo
1.6
a0
1.2
60 E D t
b 0.8
40 0
months
12
24
36
48
60
n
Figure 1. Changes in mechanical properties of foilwrapped natural rubber condoms during storage. Condoms from one manufacturer der climate-controlled relative humidity).
and production lot were stored unstorage (23°C + 5°C and 40°C * 5%
a significant (p < 0.0001) decline in strain properties (burst volume and tensile elongation-at-break) with no or little significant change in stress properties (tensile force-at-break and burst pressure). The rate of change diminished over time, stabilizing at a level that was dependent upon the mean storage temperature (Figure 2). These changes appeared to be related to heat exposure [Figure 3). The net effect of this trend is to cause the condoms to become stiffer (increased elastic modulus) during storage, a change that is further enhanced in hot climates (Figure 4). The maximum degree of stiffness reached depends primarily upon the initial elasticity of the condom-a consequence of the latex formulation and manufacturing process. When condoms were exposed to air (as in permeable plastic packages), a similar trend was observed during the first two years but was subsequently offset by aerobic degradation (Figure 4). Since changes in stress properties were relatively
months
I2
24
36
48
60
72
Figure 2. Changes in foil-wrapped natural rubber condoms stored in different climates. The indicated temperatures represent the average temperature at each warehouse over the entire storage period. All condoms were from the same manufacturer and production lot.
small or subject to other environmental influences, strain properties, particularly burst volume appeared to be the most useful parameter to assess and monitor the stiffness of natural rubber latex condoms. In these studies, initial mean burst volume of the four types ranged from 27 liters to 55 liters (inflation length 150 mm, width 52 to 54 mm). Under aerobic conditions, other trends were evident. Aerobic conditions included unpackaged condoms and condoms packaged in oxygen-permeable plastic film. Oxygen permeability of the commercial condom packages made of plastic film differed significantly (p < 0.0001) from packages containing aluminum foil (Figure 5). The rate of decline of burst pressure was significantly higher, and the shelf life Mean Burst Volume R2 = 0.450 I
28 I-
..
Figure 3. Relation between air burst volume and heat exposure of natural rubber condoms during storage. Condoms from one manufacturer and production lot were stored in sites in tropical and temperate climates.
224
Contraception 1996;53:221-229
Free et al.
2.7
I
Burst Pressure 2.5
600% Modulus 7
+ st dev
0 0 2.4
0
O
Foil Packaged __o- ---6 ___----
-
h
.
2.0
d---b 1.5
10
0.5
4
1.7 /]
0.0
0
months
12
24
36
48
60
0
72
4. Change in Young’s elastic modulus for natural rubber condoms during storage in tropical environments. Condoms from the same manufacturer and production lot packagedin aluminum foil and plastic were stored in warehouses in Pakistan and Thailand (average temperature:
months
3
6
9
12
3
6
9
12
Figure
26”C-
28°C).
significantly shorter at 45°C for plastic-packaged condoms (12 to 18 months) compared with condoms from the same production lot packaged in foil-containing materials (30 months). When unpackaged condoms of all types were stored at temperatures of 30” and 45”C, changes in airburst properties (both volume and pressure) were sufficiently high to render the condoms unfit for use within a three- to six-month period. However, no significant change could be detected in the tensile properties (Figure 6). Localized discoloration and cracking of the extreme end of the condoms could be visualized (Figure 7). This affected area lay outside the tight roll of the condom. The tensile specimens are always Burst Pressure 2.5 16.5%
Foil Package
02
I
2.0
I.
‘:‘%02
1.6%
O2
1.6%
0,
1.5
0.5 B 0.0
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1 -stdcv
4 0
months
6
12
18
24
30
5. Effect of packaging material on aging of natural rubber condoms. Condoms from the same manufacturer and production lot were packaged in all-plastic or plastic/ aluminum-foil laminate and stored in an environmental chamber at 45”C+2’C. Oxygen levels inside the packages were assessedusing gas chromatography. Figure
Break Force 85
75
65
55
1
45
i 0
months
6. Changesin natural rubber condoms exposed to air at 45°C. Condoms from two manufacturers were removed from their packages(not unrolled) and stored in an oven at 4S’C*2’C. Figure
cut from midway along the length of the condoms, well inside the rolled portion. This result suggests that the condoms were unevenly affected under these conditions. These localized changes were not evident at lower (20°C) or higher (70°C) temperatures. Silicone lubricant appeared to provide significant (p < 0.00001) protection against this localized deterioration at 30°C (Figure 8). At the temperature used for accelerated aging (7O”C), the intrinsic ability of unpackaged condoms to resist aerobic deterioration varied widely among types of condoms, indicating that some formulations relied more heavily than others upon their packaging to achieve acceptable shelf life. High humidity (above 65%RH) significantly (p < 0.00001) increased the rate of decline of burst pressure in unpackaged condoms at 70°C. Four different formulations of unpackaged (lubricated and unlubricated) condoms-aged artificially at 20, 30, 45, and 70”C-provided the basis for an analysis of the kinetics of aerobic changes in condoms during storage. Storage times ranged from 100 days at
Condom
Contraception 1996:53:221-229
Shelf Life
225
Mean Burst Volume Silicone
Lubricated
I
OJ 0
months
IO
20
30
40
Mean Burst Pressure 2.2 , t
Figure 7. Typical localized discoloration and cracking of a natural rubber condom after exposure to air at 45°C for six months. The dotted lines show the part of the condom taken for the tensile specimen. A special cutting die was developed to eliminate any edgeirregularities.
70°C to more than five years at 20°C. Of all the parameters measured (tensile and air inflation), stress parameters-most notably burst pressure-exhibited the most consistent pattern of decline over time (from 42 months at 20” and 3O”C, to 100 days at 70°C). Strain parameters under aerobic conditions were characterized by a biphasic change, increasing initially and then declining. Consequently, burst pressure was selected as the most sensitive indicator of aerobic deterioration. The rate of change (expressed as Aln Pi/PO) as a function of temperature for four condom formulations are equation, shown in Figure 9. In a formal Arrhenius this temperature-dependent rate of change is assumed analyses of the conto be constant. In our empirical
dom data, it is shown that the change in the rate of decline of burst pressure associated with temperature is quadratic and greatest at high temperatures. This quadratic function can then be used to predict degradation rates at ambient temperatures (e.g., 20°C) from
accelerated rates observed at high temperatures (e.g., 70°C). These data suggest that the reactions involved are consistent across formulations. Based upon the mean curve for these four formulations and, assuming
Sihme
I
Lubricated
1.0 $ I 0
months
IO
20
30
40
Figure 8. The effect of silicone-basedlubricant on changes in natural rubber condomsexposedto air at 30°C. Condoms from one manufacturer and dipping lot-with and without lubricant-were removed from their packagesand stored in an oven at 30°C * 1°C.
(arbitrarily) a maximum acceptable decline in burst pressure of 30 percent, the shelf life of unpackaged natural rubber latex condoms is estimated to be in the order of: six years at 2O”C, three years at 3O”C, seven weeks at 45”C, and twelve days at 70°C. The impact of impermeable, hermetically-sealed packaging on average shelf life was to increase shelf life well beyond five years at environmental temperatures. Current accelerated-aging tests for predicting shelf stability of condoms use exposure times ranging from two to seven days at 7O”C, with or without change in the minimum allowable tensile air-inflation limits. These protocols were based upon kinetic studies’ performed on 2-mm-thick natural rubber latex samples. Apparently, the first-order changes in elongation-atbreak demonstrated in that study do not apply to formed product with a wall thickness of less than 0.08 mm. The current study and recent human-use studies,3-5 suggest a new rationale for accelerated-aging studies as they apply to condoms. An aging temperature of 70°C remains meaningful. However, changes
226
Free et al.
Contraception 1996;53:221-229
Rate of Change in Burst Pmsure 0
20
Teqerature(oc)
40
60
Figure 9. Relationship between temperature and aging for natural rubber condoms from four manufacturers. The dotted line represents the mean of the four brands. The effect of impermeable packaging on this relationship is shown for one of the brands.
in inflation parameters of some formulations during the first two days of incubation at 70°C are not typical of subsequent changes (Figure 10). The test can be made more universally applicable by disregarding change in the first two days of accelerated aging. An aging period of ten days is proposed, with half the sample drawn at two days and the remainder at ten days. Since eight days at 70°C has been shown in this present study to typically reduce mean burst pressure by 20 percent, the test for an acceptable level of aerobic deterioration can be: Mean Burst Pressure,, days
Packaged
Mean Burst Pressure 2.5
1
1.0 %”
i
2 0.80 Mean Burst Pressure, dayS
A second test of the trend of condoms to become stiff at elevated storage temperatures can be applied using the volume data derived from the same test. Recent human-use studies’ with condoms of similar formulation to one of those used in this current aging study demonstrated a significant effect of stiffening on breakage during use. These data-although based upon samples of several different lots, storage sites, and ages-show a trend in burst volume over time that is similar to that seen with the comparable condoms in the current prospective controlled study (Figure 111, while burst pressure remained relatively stable in both studies. This relationship between decrease in strain properties (while stress properties remain constant) and breakage during use (Figure 12) suggests the need for a minimum batch average volume after (accelerated) aging, providing that stress properties are not unduly compromised. The data in
0.5 3
0
.
zdays
5
days
1
15
20
I.5
20
Unpackaged
Mean Burst Pressure 2.5
10
i
0.0
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5
w
10
10. Change in air burst pressureof natural rubber condoms at 70°C. Condoms from two manufacturers were stored in an oven at 70”*2’C.
Figure
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Condom Shelf Life
previously. Thus, the test for allowable stiffening after accelerated aging would Burst Volume 3 30 liters. This limit might be decreased slightly condoms (i.e., proportional to width) and dently be increased for condoms purchased and use in hot climates.
Mean Burst Volume
l
*
l
227
maximum be Mean for smaller might prufor storage
Discussion , 0
months
24
I2
36
48
60
72
84
Figure 11. Comparison of changes in burst volume of natural rubber condoms from the current study and from a recent human-use study (Steiner, Foldesy, Cole, Carter. Study to determine the correlation between condom breakagein human-use and laboratory test results. Contraception 46:279-88;1992). Condoms from a single production lot were stored in warehouses in Pakistan, Thailand, and Mexico and sampled at intervals. In the human-use study, condoms from different lots were sampledfrom several developing-world sites.
Figure 12 do not indicate
where this threshold should be set, but suggest that batch mean burst volumes of 30 liters or above are preferable. Keeping in mind that changes in modulus are most likely due to continued vulcanization, which occurs to a lesser extent after ten days at 70°C than at environmental temperatures, a minimum limit of 30 liters is proposed for burst volume following the 70°C aging protocol outlined BreakageRate 20
R2 = 0.80
1
IS -I
IO
-
5 *I
count in assessing new products. Since stress proper-
04
IS
The results of this study demonstrate that natural rubber latex condoms can be stable over many yearseven in hot and humid climates-if they are properly formulated, manufactured, and packaged. The challenge for the institutional and public purchasers or regulators is how to qualify products before purchase or distribution to be sure that they will be fit for use at any time and after any likely circumstances of shipping and storage. The current study offers some clues of what to look for in freshly manufactured products that might affect their stability and effectiveness. It also offers a new rationale for predictive shelf life testing by accelerated aging at 70°C. In addition, it provides a basis by which to analyze apparent problems with condoms that have been in storage. Current standards provide good control over leakage, and this remains an important qualifier of the product and of the manufacturing practices used to produce it. However, breakage rates are generally higher than leakage rates, and each incidence of breakage results in a higher risk of infection or pregnancy than does the presence of a microscopic hole. Since-unlike holes-breakage potential cannot be measured directly, mechanical properties like air inflation or tensile are used as surrogates. As more is learned about the stress and strain properties and their relation with breakage during use, it is important to modify standards, specifications, and buying practices to take advantage of that new knowledge. From the current aging study and human-use studies, it has become apparent that the elastic modulus (or stiffness) of the latex film must be taken into ac-
20
liters mean burst
25
30
35
volume
Figure 12. Relation between air burst volume of natural rubber condoms and breakage during use. Condoms are essentially equivalent to manufacturer 1 in the present study but represent multiple lots stored in several overseassites. Adapted from Steiner, Foldesy, Cole, Carter. Study to determine the correlation between condom breakage in human-useand laboratory test results. Contraception 46:27988;1992.
ties (measured as burst pressure or force-at-break) change very little in well protected condoms, these strain properties-particularly burst volume-are good surrogates for elastic modulus. From the most recent human-use study,5 it appears that when strain properties fall below a certain level, breakage during use increases dramatically (see Figure 12). The current study shows that burst volume of protected condoms declines in the first one to three years of storage, eventually stabilizing at a level that is inversely related to storage temperature. In view of these findings, buyers should qualify new condoms in relation-
228
Change
Free et al.
(%)
Contraception 1996;53:221-229
Shelf Vulcanization
Change
(%)
Localized Degradation (Aerobic)
Pressure Fame
n
Change (40)
General Degradation (Aerobic)
Figure 13. Patterns of change in ultimate stressand strain properties of natural rubber condoms under different aging conditions. (A) At environmental temperatures (data shown is from 20°C storage),a decline in strain properties with little or no changein stressproperties occurs under anaerobic conditions and in condomsexposedto air but resistant to oxidation. This pattern of change is consistent with the continuing formation of sulfur-sulfur crosslinks (vulcanization) and lead to an increasein elastic modulus (stiffness). (B) At high environmental temperatures (3045”C), a rapid decline in air-inflation properties occurs in the rolled condom exposedto air through broken or highly-permeable packages.Tensile properties are unaffected becausethe section of the condom used for this test is protected by the many layers of latex film in the rolled portion. Apparently, the rate of oxygen uptake at the exposedsurface exceedsthe rate of diffusion through the latex film at the temperatures. (C) Stress properties of rolled condoms exposedto air at any temperature through broken or permeable packagesdecline steadily and provide the best means to monitor oxidative changesin stored condoms. At higher temperatures or in condomswith a low resistanceto oxidation, strain properties may initially increasebefore eventually decreasing (data shown are from 70°C storage). ship to a minimum mean or median burst volume, according to a protocol such as the one proposed here. The changes in modulus discussed above represent postproduction curing of the latex film rather than actual degradation. By contrast, the aerobic breakdown of the latex film is true degradation. However, there are several effective means to prevent or minimize this type of change. These include antioxidant, silicone lubricant, and impermeable (usually containing aluminum foil) packaging. Since the protective effect of these is additive, there is no reason why properly formulated, cured, and packaged condoms cannot
be made to last five years or longer-even
in tropical
and other harsh environments. Qualification of newly manufactured products include specifying aluminum-foil laminates as packaging materials, checking for intact package seals, and specifying silicone lubricant. A test for resistance to oxidation has been proposed based upon aerobic kinetics of four brands of US-manufactured condoms. Buyers for tropical and other harsh environments can augment the proposed test by including condoms removed from their packages. Using this augmented test-comparing results from unpackaged and packaged condoms-an assessment can be made of the package dependency of the product. It seems prudent for these challenging con-
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Condom Shelf Life
ditions to purchase condoms that will stay in good condition even if the package is compromised. Problems have occurred with stored condoms due to actual changes in properties or perceived poor performance. In many cases, these have been hard to assess. Many of these cases have involved discoloration, odor, or package changes that negatively affect user acceptability. In some cases, these have been a consequence of excess stiffening or of aerobic degradation. Based upon the present study, a “thumbprint” of the product can be used to analyze the type of changes that may have taken place assuming that the test data on samples of aged product can be compared with data obtained when the condoms were new (or from contemporary new product of the same make). Figure 13 illustrates the changes in air-inflation and tensile parameters when different aging factors predominate. A fall in strain parameters (with little or no change in stress parameters] suggests that the condoms are well protected from aerobic degradation but have undergone shelf vulcanization-resulting in a stiffer condom. A pronounced fall in air-inflation parameters (with little or no change in tensile parameters) suggests localized deterioration, high-temperature exposure, and poor packaging. A fall in stress parameters (with less or no fall in early strain parameters) suggests a lack of intrinsic (antioxidant) protection and oxygen-permeable packaging. In most cases, more than one of these factors may be operating at the same time so that the picture may not be as clear. However, all of these “thumbprints” have been observed by the authors in tests of aged condoms over the past 20 years.
Acknowledgments This research was supported Food and Drug Administration
by the United States by contract with the
229
Washington State Board of Pharmacy. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. Partial support for this study (package type at 45°C) was provided by Family Health International (FHI) with funds from the United States Agency for International Development (USAID), although the views expressed in this article do not necessarily reflect those of FHI or USAID. The constant diligence of PATH laboratory staff was critical to conducting the research. Thanks go to the National Research Institute of Fertility Control, Karachi, Pakistan; Gonoshasthaya Pharmaceuticals, Limited, Dhaka, Bangladesh; Northwestern Drug Company of Auburn, Washington; and the City of Seattle Public Health Department for serving as study sites.
References 1. Belsky RL. An assessment of reported condom deterioration in Bangladesh. A report supported by United States Agency for International Development (AIDS) AID/DSPE-C-0053, 1982. 2. Mandel J, Roth FL, Steel MN, Stiehler RD. Measurement of the aging of rubber vulcanizates. J Res Nat1 Bureau Std 1959;63C:141-5. 3. Free MJ, Skiens EW, Morrow MM. Relationship between condom strength and failure during use. Contraception 1980;22:31-7. 4. Free MJ, Hutchings J, Firman L, et al. An assessment of burst strength distribution data for monitoring quality of condom stocks in developing countries. Contraception 1986;33:285-99. 5. Steiner M, Foldesy R, Cole D, Carter E. Study to determine the correlation between condom breakage in human use and laboratory test results. Contraception 1992; 46:279-88.