Extractables & Leachables case study – Extractables study on filters for pharmaceutical manufacturing
Once again, our expertise goes beyond packaging.
Extractables can be obtained not only from the packaging system of the drug product, but also from 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?
The sample is a filter – used during the production of inhalation pharmaceutical products – characterized by a hydrophilic membrane. All its components are listed below:
- Materials-cage/core: rigid polypropylene
- Materials-Membrane filter: modified polyvinylidene fluoride (PVDF)
- Materials-Support web: spun-bonded polypropylene
- Materials-O-rings: silicon
Filtration processes are a critical point for the pharmaceutical industry. Proper filtration makes sure that the products manufactured are safe for patients, and ensures that manufacturers are not losing valuable products due to improperly working filtration processes. Product safety is fundamental in pharmaceutical production, which means that the highest quality standards have to be guaranteed. The filtration systems and filters that are used have to be effective in the filtration of aggressive fluids at multiple points in the process.
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 filters 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). The study conducted may also represent an investigation into the presence of possible substances unintentionally added as possible process contaminants or impurities.
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
Results of the study did not reveal any organic compound above the analytical evaluation threshold AET. Moreover, no elementary impurities and no anions were detected at concentrations above the limit of quantification of the instrumental method.
Considering that the analytical strategy had been developed on the basis of a threshold – the AET – that serves specifically to discern what compounds need a toxicological risk assessment, and considering that no compounds were detected above this threshold, the need for a toxicological evaluation could be forgone.
