Q Have sterilization methods for disposables and single-use systems changed in recent years?
A No. Gamma irradiation is still the most common sterilization method for disposables and will continue to be, because gamma
irradiated single-use systems are supplied to the end user pre-assembled and pre-sterilized. This reduces labor, especially
as systems grow more complex. Most disposable components also can be autoclaved with the exception of bioprocess bags. Steam
sterilization is not suitable for single-use technologies. However, a few filter types can withstand this method of sterilization.
Table 1. Operating scale of single-use technologies
Q What type of documentation is provided to demonstrate that systems have been irradiated at the right dosage?
A The irradiation company provides a certificate of irradiation to demonstrate that the single-use system has been irradiated
to dose- range specifications. If any aspect of the single-use system is changed, including size, density, thickness, packaging,
etc., it is critical that dose mapping be performed again to the exact specifications of the modified single-use system and
its package. Dose mapping ensures that the level of irradiation falls within the appropriate window of irradiation for each
component within the disposable assembly. Although the irradiation range varies from system to system, the usual gamma irradiation
dose for any single-use system is typically a minimum of 25 kiloGrey (kGy) and the maximum is 50 kGy.
Q What is the difference between extractables and leachables?
A By definition, extractables are potential solutes derived under worst-case conditions from the drug product or process fluid
contact materials, typically using model solvents. Leachables comprise the subset of contact material solutes detectable in
actual product or process fluids. Leachables may also be generated through the interaction of products and contact materials
over time. Solvent and temperature conditions, among other factors, determine whether extractables or leachables are generated.
Extractables represent the potential for soluble materials to leach from the disposable component under extreme testing methods,
but would not otherwise be released into the product during normal processing. By contrast, leachables, which are drug product
or process fluid-specific, are released into the product under normal processing conditions.
Since leachables pose an inherent contamination threat, the single-use industry generally uses the term "extractables" when
describing soluble materials that could be released from a disposable component. It is important to note that there will always
be some level of extractables present. The goal of extractables testing is not to demonstrate their absence, but to make sure
that they will not adversely impact the quality, safety, or stability of the drug.
Q What are the common methods for testing extractables?
A A wide range of tests can be performed to assess and characterize extractables. Factors determining extractables include
the materials used, attributes of the solvent, and processing conditions such as time, temperature, and sterilization. Thermodynamic
properties, including the solubility, diffusion rate, and degradation rate of processing materials, also play a role.
Although the results of many of these tests are provided in documentation from the supplier, additional testing may need to
be performed by or requisitioned by the end user. This depends on the criticality of the application and the manufacturer's
specific knowledge of the product. For example, manufacturers may want to do some specific product validation testing for
formulation and filling applications to demonstrate to the FDA that proper toxicity studies have been performed. Manufacturers
can turn to process integration companies, including disposable equipment suppliers, to perform these studies.
Q Do I need to perform these studies for each single-use system?
A No. It would depend on the criticality of the application and the level of existing validation information data for each
single-use component. It is recommended that end users work with the system integrator to determine whether a process specific
study is required. Following are recommendations for performing extractables studies on filters, bags, and integrated systems: