VALIDATION OF STERILE PACKAGE INTEGRITY 1
Package integrity is validated by sterility testing. At present there are no recognized methods for performing a whole package microbial challenge; therefore the package may be validated indirectly (e.g., using methods for detecting physical leaks). Several methods are commonly used to test sterility.
Nondestructive method:- This involves determining packaging integrity by visual inspection of package seals, and is only suitable for packages with at least one transparent material component. It uses high-intensity light to observe the continuity and uniformity of the seal. For packages incorporating heat seal adhesives, the attributes of integrity have a direct relationship with the process parameters, process equipment, and packaging materials. Visual inspections are very suitable for production in-process controls of quality assurance.
Destructive methods:- For use in validating packaging for their integrity these include:-
- Positive pressure/submersion
- Dye penetration
- Vapor/particle leak testing
- Vacuum Leak Testing: ASTM D-3078—Leaks in Heat Sealed Flexible Packages:- The standard procedure is applicable to some medical device packages. The method is useful for detecting gross leaks in packages and may miss very small leaks. For porous packages that do not produce an internal pressure under vacuum due to escaping air the method may not work well. In addition, on releasing the vacuum, water may permeate the package. A nonporous pressure-sensitive label can be used to cover porous surfaces and make then impermeable, whereby the vacuum test may be effective.
- Positive Pressure Testing:- By applying positive pressure to a package submerged under water, gross leaks can also be detected by the issuing bubbles at damaged seals or pinholes in the nonporous component of the package. A degree of air permeation through the porous component is allowed on condition that it does not affect observation of leakage in other components of the package.
- Dye Penetration Testing:- This test is intended to detect channels, open pathways, or discontinuity in a sealed area specified as a critical primary barrier. Pinholes in nonporous materials are also detected. This method is suitable for both flexible and rigid packages and with porous and nonporous materials. When a penetrating colored dye solution is injected into a package it detects channels or voids in the sealed area via capillary action and pinholes in nonporous materials via blotting on a paper tissue. Packs with at least one transparent component are more suitable for viewing the results. Dye penetration is more difficult to use on packages of porous materials, such as paper.
- Injection of Particle Vapor Testing:- Theoretically smoke or vapor injected under slight pressure from a smoke chamber into a package will find imperfections and channels in the seal and deposit particles at the locations of leakage. This method is difficult to perform, as the results are subject to misinterpretation, and are of questionable value for general use.
Package Integrity and Performance Test Methods:- The seal and burst test values of identical packages produced on a specified validated production packaging line are useful data for performance specifications. The standardized methods of the American Society for Testing of Materials (ASTM) may be used.
- Seal strength test:- ASTM F88 – Seal Strength of Flexible Barrier Materials:- A specified width (1 in. 2.54 cm) strip is cut from the seal of the package. Each side is clamped on a tensile tester and the peak force is recorded during complete separation of the material at the seal. Samples from several points on the package (as well as the material supplier’s seal, when present) should be determined. The standard gives typical values for seal strength, but an optimum seal strength will depend on the type of package being tested and the specific application. This test does not measure the continuity of the effectiveness of the seal.
- Burst test: ASTM D-1140—Failure Resistance of Unrestrained and Nonrigid Packages for Medical Applications. The standard provides two methods for determining the ability of the packaging material or seals to withstand internal pressure. The burst test forms a basis for determining overall package integrity after dynamic events.
- Open package test:- The open end of the pack is clamped in such a way that pressure can be increased into the package at a greater rate than the permeability (of porous components) until failure occurs. The type and location of failure and the pressure at which it occurred are recorded. This test is useful for incoming material inspection as part of the quality assurance procedures.
- Closed package test:- This test is performed on production samples as an in-process quality assurance procedure. The sealed package is used. Pressure is inserted through a component and increased until failure occurs. The location and type of failure and the pressure at which it occurred is recorded. The standard gives typical burst test values. There is as yet no correlation between burst test and seal strength values. It has been shown, however, that the variation in expansion of packages produced from flexible materials can lead to inconsistent test results, and more consistent results are obtained by restraining the expansion of the packages; for example, by fixing them between parallel plates.
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