The composition of the process stream will also contribute to the overall risk of leachables and extractables occurring. Because
plastics are not typically compatible with all chemicals, the process stream extraction risks can be higher depending on the
solvent and chemical concentration of specific components. First and foremost, the chemical compatibility of each of the
single-use components must be understood to ensure that the process stream does not contain chemicals that will adversely
affect the disposable item. Additionally, as the pH moves away from neutral to either alkaline or acidic, the risk increases
for leachables to occur. For example, a 1N NaOH solution will pose higher risk than one of 0.1N.
In addition to concentration and material incompatibility, the temperature of the process stream can affect the risk of leachables
and extractables being transferred into the product. Typically, the extractables qualification tests include elevated temperatures
because, as temperature increases, the extraction risk increases as well. Conversely, lower process temperatures provide the
least risk of this occurring. Additionally, the single-use item may be exposed to heat during the serilization process. If
the item is heat-sterilized, there may be a greater risk of transferring extractables to the process stream.
How the drug product will be used will also play into the overall risk of leachables and extractables. Although typically
how the drug product is used cannot be adjusted to reduce the risk, the qualification activities may be increased to ensure
that the single-use item is safe to use for the process. The risk assessment should consider what the final dosage will be
and how often the patient will receive the drug. The more of the drug product the patient receives, the greater the exposure
to potential leachables and extractables; therefore, the risk is greater. Route of administration needs to be considered.
If the product is an injectable then the risk is much higher than if the product is a topical agent.
What is already known about the single-use item should be used in the risk assessment. Vendor-supplied data should be analyzed
for the material safety risks. Material safety risks serve to document what is currently known about the materials of construction.
Again, the risk assessment needs to ensure that all component parts on the single-use item are accounted for within the vendor
qualification package. Toxicity and/or biocompatibility (USP class VI classified) testing should have already been performed
and documented. All components should be Animal Derived Component Free (ADCF) or EMEA 410/01 compliant. A great advantage
to the risk assessment for implementing single-use items is that vendors will have their own extractable studies that can
be referenced. A toxicologist should review the extracted substances to determine if they are acceptable. The conditions under
which the extractable tests were performed should be observed; the manufacturing process might not get anywhere near these
conditions but keep in mind that these tests are performed at worst-case conditions to see what can be extracted. Another
thing to look for in the vendor qualification package is to see if the plastics are certified under Code of Federal Regulations (CFR) 21. 177. Although this certification is for food contact surfaces, it can reduce the overall risk because the plastics were
derived from a more controlled process. A summary of key risk factors is illustrated in Table I.
Table I: Key risk factors for single-use components.
Qualification activities maybe reduced depending on risk to the process/product. Each qualification activity should be looked
at individually with respect to how the single-use item will be used in the process and how high it scored on the risk assessment.
Not every single-use item will need to undergo leachable testing if the risk score is low enough, which saves time and capital
for the single-use item implementation. Keep in mind that if one component on the single-use assembly scored higher than the
other component parts, it may be possible to have the suggested qualification activities performed on just that part and not
the entirety of the assembly.