Securing and Qualifying Single-Use Technologies - The authors suggest techniques for mitigating risk and securing the supply chain for single-use components used in biopharmaceutical manufacturing. -

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Securing and Qualifying Single-Use Technologies
The authors suggest techniques for mitigating risk and securing the supply chain for single-use components used in biopharmaceutical manufacturing.


BioPharm International Supplements
Volume 26, Issue 4, pp. s18-s23

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.


Table I: Key risk factors for single-use components.
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.

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.


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