A standard matrix with a large number of solvents usually can be referenced for the initial evaluation of the compatibility
of a film with a solution. If a container is to be used with a solution that is not on this list, two options are available,
depending on the process risk analysis. The first option is to compare the new solution with a solution that has been tested
already. If the solutions are similar, then the compatibility can be considered similar. The second option is to conduct a
study with the specific solution and under the specific conditions of use.
Abbreviations and Definitions
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Extractable and leachables. The purpose of extractables and leachables studies is to determine the possible impurities (extractables or leachables) that
can come out of the films. A model solvent approach is commonly used to determine the amount and type of extractables under
conditions that are more aggressive than normal operating parameters. A leachables study is normally carried out with a specific
solution and conditions (time and storage) that are similar to operating parameters. The types of tests that are usually carried
out will make it possible to identify and quantify volatile, semi-volatile, and nonvolatile products as well as heavy metals
that can be leached from the film. Once again, a process risk analysis will determine the extent of these studies, mainly
depending on the proximity of the process to the final drug delivery.
Protein adsorption. Protein adsorption can be approached in two general ways. The first approach is to conduct classical potency testing at various
stages of product storage and then determine if any adsorption has taken place. The second approach can be used as a basis
to estimate the potential loss of proteins upon contact with the film's surface. This second approach quantitatively evaluates
the amount of "model" proteins that can adhere to a polymeric surface and compares that to the amount that can adhere to a
glass surface.48
Product integrity
Regardless of the production step in which a single-use container is used, the physical and microbial integrity of the complete
product must be guaranteed. Depending on the production stage, this guarantee can be achieved in various ways. A 100% leak
test conducted before use can be considered the ultimate guarantee. In some cases, however, this type of testing can be destructive
or weaken the product. The highest level of integrity guarantee is achieved by having a capable and validated manufacturing
process. Common tests used to conduct process validation on single-use equipment include seal testing, burst testing, drop
testing, air leak testing, ship testing, and microbial ingress testing. These tests are generally described in well known
standards (e.g. ASTM, ISO).
Most importantly, it is the final product that is validated and not its individual components (films, connectors, tubing,
etc.). The integrity of the product is determined by its weakest link; it is not necessary to have bag seals that are twice
as strong as the connection of the tubing to a bag, because the connection will fail long before the seals are stressed.
Expiry dating
Product aging needs to be considered for most of the tests and qualifications mentioned above. Polymeric materials are known
to age and their physical and compatibility properties may change with time. These changes can be increased by gamma irradiation
and need to be measured either through natural ageing or under accelerated ageing conditions.49
Examples of Polymer Choices for Single-Use Applications
Example 1:
Input data: Need to store 200 L of product for two to four weeks at 2 to 8 °C. Solution is at pH 5, needs mixing, and is sensitive to
oxygen. Container needs to be aseptically filled.
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