In previous episodes of the Alioth“Core Insights” knowledge series, we revealed the origin of the 0.22 μm pore size for sterilizing-grade filters and provided an in-depth analysis of the working principles of liquid and gas filtration, as well as the factors affecting filtration performance. So, why do we need to understand so many filtration principles? Today, let’s unveil the answer!
Why Do We Need to Understand So Many Filtration Principles?
Because these principles directly impact patient safety, drug quality, and costs.
Filters Can Be a Source of Particulate Contamination
Particulate matter in injectables must be strictly controlled; otherwise, it may trigger serious adverse reactions. The risks of particulate contamination during filter manufacturing, installation, and usage should be fully considered and assessed. If not properly controlled, the filtration process may instead become a source of contamination.
Absorption by Filter Membranes
The absorption of drug components by filter membranes may also affect product quality. The figure below summarizes the factors influencing filter membrane adsorption.
Filters Can Be a Source of Extractables/Leachables
Leachables generated by terminal filters may affect formulation stability, and some leachables may even be toxic. Protein formulations are particularly sensitive; leachables are often unstable, which may increase protein aggregation and oxidation of protein structures.
Different types of filters may introduce different extractables/leachables. For example, PVDF filters may generate hydroxypropyl acrylate oligomers, propylene glycol, and crosslinkers such as tetraethylene glycol diacrylate; mixed cellulose ester filters may generate glycerol. Additionally, studies have found that some filters produce N,N-dimethylacrylamide, a substance typically used as a binder, which was ultimately traced to the filter housing rather than the filter membrane itself. This also indicates that when conducting extractables/leachables assessments, drug-contact materials other than the filter membrane should also be considered.
In pharmaceutical manufacturing, a wide variety of filters are used, ranging from depth filters and pre-filters with various nominal pore sizes to sterilizing-grade membrane filters validated for sterilization. When selecting filters, specific process conditions are usually taken into account. Therefore, fully understanding different filtration principles and the various factors affecting filtration is crucial for ensuring patient safety, guaranteeing quality, and controlling costs.