Extractables & Leachables case study – Extractables study on silicone tubing used for drug products manufacturing
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Extractables can be obtained not only from the packaging system of the drug product, but also from systems and components used during the manufacturing process that come into contact with the drug product itself before the final packaging.
Manufacturing processes use components and parts that may be fully or partially constructed from plastic materials. By entering into contact with the process stream, these components could interact with the pharmaceutical product, leading to the accumulation of process equipment-related leachables (PERLs) in the process stream, and may alter the effectiveness or efficiency of subsequent processing operations.
What about the system?
In this case the sample was a silicone tube for multiple use. The tubes are be used during pharmaceutical production for a specific number of weeks per year for a couple of years, except in the case of damages to the tubes themselves. Tubes are washed with water, and autoclaved after each use. The contact time between the tubes and the pharmaceutical product is also predetermined.
Aim of the study
The study can be considered a “worst case” approach, due to the contact conditions and to the nature of the extraction media, and its aim is the characterization of extractable compounds possibly released by silicone tubing for pharmaceutical manufacturing. The extractables were characterized if present in a concentration higher than the Analytical Evaluation Threshold (AET), calculated on the basis of an appropriate Safety Concern Threshold (SCT).
Mérieux NutriSciences strategy for Extractables & Leachables studies
Safety of the pharmaceutical product must be ensured throughout the whole production chain, considering also system components as an integral part of the study approach.
- Extractables & Leachables study
- Toxicological evaluation
- Identification of probable pharmaceutical risks
The analysis of the extracted substances considered both organic and inorganic entities. The chromatographic techniques used for screening are coupled with appropriately sensitive, universal, and information-rich detection methods to ascertain the extractables identity and concentration, applied as follow:
- HS-GC/MS – Headspace Gas Chromatography coupled with mass spectrometry detector
- GC/MS – Gas Chromatography coupled with mass detector
- HPLC/HR-MS Q-Orbitrap – Ultra Performance Liquid Chromatography coupled with high resolution mass detector
- ICP/MS – Inductively coupled plasma coupled with mass detector
- IC – Ionic Chromatograph with conductivity detector
Results
The results obtained have been subjected to a toxicological evaluation to establish the safety of the tubes or the need for further investigations.
- No elementary impurities investigated showed values higher than the quantification limit, except for the element boron.
- No anion showed values higher than the LOQ of the method.
- No organic compounds VOCs, SVOCs, NVOCs investigated in the extraction media were present in a concentration equal to or higher than the analytical evaluation threshold “AET”.
