Absorption refers to the process by which certain components in the fluid to be filtered adhere to the filter membrane (or filter device), potentially affecting the composition and concentration of the filtrate.
Absorption materials in filters include the filter membrane, housing, and support structures. Factors such as flow rate, filtration duration, concentration of the fluid to be filtered, preservative concentration, temperature, and pH may all influence absorption.
For filtration processes where absorption is relatively high but still acceptable, a surge tank can be used to collect the product before final filling, thereby minimizing the impact of absorption on product concentration. During process development, absorption studies are typically conducted at small scale and subsequently confirmed during scale-up. These studies can also be used to establish potential pretreatment procedures (e.g., buffer rinses, soaking), define operating parameters, or guide membrane material selection.
The impact of absorption should also be considered in bioburden reduction and pre-filtration processes. The Guidelines for Sterile Filtration Technology and Application, issued by the Center for Drug Evaluation of the National Medical Products Administration (NMPA) in 2018, states: “Verification shall be conducted to confirm that the bioburden reduction filter does not adversely affect the drug solution. Validation of the bioburden reduction filtration process may be performed as part of the overall product process validation… Validation of the bioburden reduction filtration process shall include chemical compatibility, extractables/leachables, and absorption studies.”
A common issue in absorption studies is the absorption of preservatives. Many pharmaceutical processes incorporate preservatives to inhibit or destroy microbial growth; however, preservatives are readily adsorbed by filters and related materials, which may lead to reduced or lost preservative efficacy.
Benzalkonium chloride (BAK) is frequently used as a model preservative in absorption studies because it possesses both hydrophobic and electrostatic properties. Numerous experimental studies have demonstrated that BAK absorption by filter membranes is related to both the membrane composition (material) and the physicochemical properties of BAK itself. Screening and testing among commercially available membrane materials can typically identify filter elements with relatively low absorption. Furthermore, formulation-related factors, such as avoiding the use of salts, and process-related factors, such as pretreating the filter membrane, can further reduce BAK loss. If active pharmaceutical ingredients (APIs) are present in a specific formulation, potential interactions between BAK and the API should also be evaluated, as competitive absorption between BAK and the API may occur.