Point-of-Manufacture Sterilization

A look at the material compatibility of Eastar 6763 copolyester with vaporized hydrogen peroxide sterilization.

Jennifer Lauderback, James Fraser, Erick Gustin, Gerald McDonnell, and Kevin Williams

Despite the range of methods widely used for medical device terminal sterilization, no one offers the perfect solution for every application. For example, steam sterilization may be overly aggressive to construction or packaging materials, including forming stress cracks on metal components, and cannot be used for heat-sensitive devices. Gamma irradiation or E-beam sterilization are certainly reliable alternatives for low-temperature sterilization, but are generally only performed on a contract basis at a limited number of facilities, which adds transport and storage costs. For integration into a manufacturing line for on-site sterilization, ethylene oxide (EtO) is an alternative, but cycle times are relatively long (in particular for poststerilization aeration), and toxicity and carcinogenicity issues are often a significant concern.

An emerging process for point-of-manufacture sterilization is low-temperature vaporized hydrogen peroxide (VHP). This method uses hydrogen peroxide vapor alone, under vacuum. In addition to rapid sporicidal activity, VHP demonstrates low toxicity and rapidly decomposes into nontoxic by-products (water vapor and oxygen), offering a safer and rapid alternative.

Atmospheric application with the VHP 1000 biodecontamination series has been widely used and validated in industrial applications for more than 10 years for the decontamination of sterility testing environments, production filling lines, biosafety cabinets, rooms, and other enclosed areas. The VHP process is a rapid, low-temperature, dry sterilization process1,2. A single mobile or modular system generates, delivers, controls, and removes VHP for an enclosed environment. During the sterilization phase of the cycle, the system maintains hydrogen peroxide in a dry vapor form to maximize efficacy in the given environment and continually removes and replenishes vapor concentrations over the programmed cycle.

Vacuum applications have also been developed to increase the penetration of the vapor. For example, the VHP 1000DV is a mobile system for freeze dryer and aseptic filling line sterilization3,4. The VHP MD series is based on similar vacuum technology and allows for the terminal sterilization of simple and complex medical devices. The series is available in a variety of customized chamber sizes, with a touch screen control and a variety of accessories such as easy-loading baskets and carts, and biological indicators.

A typical VHP MD sterilization cycle includes an optional leak test, conditioning, sterilization, and aeration. The leak test, if performed, holds the sterilization chamber under vacuum for a preset time and monitors the pressure to detect leaks. The conditioning (or drying) phase uses the vacuum system to dry the chamber/load and condition the load temperature for sterilization (generally in the range of 25° to 50°C).

The sterilization cycle involves the drawing of a deep vacuum, the injection and diffusion of VHP, and then the bleeding of dry air or nitrogen to the sterilization set-point pressure (150–700 torr). VHP is prepared by direct vaporization of a 35% hydrogen peroxide solution (Vaprox). Similar to the atmospheric applications, the hydrogen peroxide concentration is kept below the saturation point to prevent condensation on the device surface and maximize the antimicrobial activity and material compatibility of VHP. The actual number of sterilization pulses for each application will vary depending on device design, load size, and materials of construction or packaging. Finally, during aeration the vacuum system is used to rapidly remove VHP from the chamber by a series of vacuum/air pulses. Unlike EtO, no further aeration time is required, minimizing the overall time and cost for product availability. Although the overall cycle time may vary depending on the application, it is generally two hours or less.

Previous industrial experience has shown that VHP is compatible with and safe for use on a wide range of materials typically used for medical device construction, including metals such as 300-series stainless steel, aluminum, and titanium; plastics such as polypropylene, polyethylene, and polycarbonate; and other materials such as silicones, glass, and electronics. In this report, the compatibility of a widely used medical device packaging material with VHP has been in-vestigated and analyzed following a typical cycle.

MATERIALS AND METHODS

The material chosen for this study was based on a typical representative sample of the materials of construction used in medical device packaging. Eastman Chemical Co. (Kingsport, TN) provided 10-mil Eastar Copolyester 6763 (PETG) samples.

All materials were exposed to two typical VHP MD sterilization cycles, developed at 30°C. All exposures were conducted in a 5.00-ft3 (0.14-m3) chamber. Following a successful leak test, two conditioning pulses were performed to equilibrate the chamber and contents for temperature and humidity. This was accomplished by evacuating the chamber to 1.0 mmHg, holding the vacuum for 30 seconds. Then the pressure was raised to ambient by allowing warm, dry air to fill the chamber.

The sterilization phase consisted of evacuating the chamber to 1.0 mmHg and introducing VHP by vaporization of 1.2 g of 35% hydrogen peroxide. The vapor introduction into the chamber caused a slight pressure rise to around 10 mmHg. The initial vapor concentration was 2.0 mg/L, which at 30°C is equivalent to 80% saturation. The vapor was held at this pressure for 5 minutes and then raised to 538 mmHg by introduction of warm, dry air into the chamber. Chamber contents were further exposed for an additional 5 minutes at this pressure and then evacuated by pulling the chamber pressure back to 1 mmHg. This sequence was repeated for a total of three injection pulses. After the sterilization phase, six aeration pulses were used to aerate the chamber. Each of the aeration pulses consists of evacuating the chamber to 2.3 mmHg and holding for 30 seconds, followed by transitioning to 654 mmHg.

The total cycle time was 90 minutes, which used a total weight of 3.6 g of 35% hydrogen peroxide.

RESULTS AND DISCUSSION

Eastman performed the functionality assessment of the Eastar Copolyester 6763 before and after the VHP sterilization process. The physical property results are shown in Table 1.

 
Eastar 6763
Test MethodEastar 6763 Control
Eastar 6763 Sterilized
IhV (Inherent Viscosity)
0.713
0.71
Haze, %ASTM
D 1003
0.99
0.7
Gloss @ 45%, units 
110
109
Transmittance, %
  Regular
  Total
ASTM
D 1003
90
92
90
92
TransparencyASTM
D 1746
100
100

Tensile Strength @ Yield (MPa), MD

ASTM
D 882
50.2
49.7
Tensile Sterngh @ Break (MPa), MDASTM
D 882
66.3
71.1
Elongation @ Yield (%), MDASTM
D 882
4.6
4.6
Elongation @ Break (%), MDASTM
D 882
339*
383*
Tensile Modulus, MD
  1% Secant, MPa
  Tangent, MPa
ASTM
D 882
1835
1915
1815
1905
Dart Impact,
Failure Weight, gm
   23°C
  -40°C

ASTM
D 1709A

Method A

457
406
473
492
Impact Resistance
  Energy @ Max Load, J
  Fracture Energy, J
ASTM
D 3763
2.7*
3.02*
2.34*
2.75*
DSC - Tg, °C
2nd Heat
 
83
82
Color
  L*
  a*
  b*
 *-CV%>10%
ASTM
D 2244
96.15
-0.01
0.34
96.13
0
0.34
Table 1. Physical property results

Steris Corp. (Mentor, OH) retained samples and performed hydrogen peroxide residual analysis to determine the levels of hydrogen peroxide absorbed by the materials during exposure. Five test coupons from each material were removed from the chamber immediately after the cycle and placed into 10 ml of deionized water at 25°C. Following sonication and vortex mixing, the samples were allowed to stand for 60 minutes. The extract was then analyzed using a Xylenol Orange Assay to assess the hydrogen peroxide levels. A second extraction procedure was done to ensure complete removal of all hydrogen peroxide from the test piece. Residual levels were then determined in both mg/L and µg/cm2 (Table 2). Residual levels for most of the materials ranged from 0.23 mg/L to 32.61 mg/L.

Sample
Surface Area (cm)2
Extraction
volume (ml)
H2O2
LEVELS (mg/L)
H2O2
LEVELS (μg/L)
Estar Copolyester 6763
(control—unsterilized)
32.5
20
0.23
.07

Estar Copolyester 6763
VHP sterilized)

32.5
20
32.61
10.01
Table 2. Hydrogen peroxide residual levels

Residual testing showed all materials were below the safe and acceptable limit for hydrogen peroxide of 500mg/L. Hydrogen peroxide is approved for use and widely used in toothpastes, mouthwash and as a food additive in concentrations of 500 mg/L. Further, it is available for household use as a disinfectant/antiseptic at 30,000 mg/L. These safe levels are in contrast to significantly lower safety limits with EtO. The levels observed in this study were all significantly below hydrogen peroxide safety levels and, in the case of absorptive materials, could be further reduced by additional cycle aeration pulses or storage at room temperature.

CONCLUSION

The VHP MD sterilization process was shown to be compatible with the materials tested. The physical and chemical properties of the materials showed little to no change following exposure. The process did not affect material strength. Chemical results show no changes observed with the test samples.

Overall, these results are not surprising as VHP is a dry sterilization method and has been widely used in similar atmospheric and vacuum applications for decontamination and sterilization, including sensitive materials like electronics. VHP is a safe, rapid, and material-compatible alternative for low-temperature medical device sterilization.


REFERENCES

1. A Malmborg, M Wingren, P Bonfield and G McDonnell. "Room decontamination with vaporized hydrogen peroxide." Cleanrooms. In press (2001) .

2. J Krause, G McDonnell and H Riedesel. "Biodecontamination of animal rooms and heat-sensitive equipment with Vaporized Hydrogen Peroxide." Cont. Topics. 40 (2001):18–21.

3. NA Klapes and D Vesley. "Vapor-phase hydrogen peroxide as a surface decontaminant and sterilant." Appl. Environ. Microbiol. 56 (1990): 503–506.

4. JW Johnson, J Arnold, S Nail, and E Renci. "Vaporized Hydrogen Peroxide sterilization of freeze dryers." J. Parent. Sci. Tech. 46 (1992): 215–225.

Jennifer Lauderback is a senior market development representative for Eastman Chemical Co. James Fraser is a technician associate for Eastman Chemical Co. Erick Gustin is a senior scientist for Steris Corp. Gerald McDonnell is research and development director for Steris Corp. Kevin Williams is a scientist for Steris Corp.

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