Lifetime studies for membrane reuse remains a critical issue for biotech companies producing therapeutic and diagnostic products. Two approaches commonly used for establishing membrane lifespan are prospective validation and concurrent validation. Creation and qualification of the scale-down model, and performance of small-scale reuse studies to support prospective validation, is time-consuming and costly. However, if a high likelihood of cleaning failure exists, performing these studies may be essential and may prevent loss of manufacturing lots at scale. For certain cases, concurrent validation may be more appropriate and performing an identical testing regimen in the form of routine in-process testing may provide the same, if not higher, levels of assurance for lifetime membrane performance. A production schedule may be significantly influenced when additional sampling and testing are required between lots. Therefore, a cost–benefit analysis should be performed to determine which validation approach, prospective or concurrent, is more appropriate and also how many reuses should be targeted.
Cleaning procedures, and possibly steam sanitization procedures, are routinely performed before membrane use. Depending on the specific application and process involved, membrane performance and functionality may be adversely affected over time.
The topic of reuse of membrane media, unlike the topic of reuse of chromatographic media, has not received much attention in the literature. The present article is the ninth in BioPharm International's "Elements of Biopharmaceutical Production" series, and it presents approaches toward establishing and demonstrating lifetimes for membrane media.
KEY PROCESS PARAMETERS TO ASSESS MEMBRANE PERFORMANCE
An appropriate subset of parameters should be chosen when planning a reuse study. These parameters should be based on the purpose of the intended application. This section briefly discusses some important process parameters commonly used to assess the performance of a membrane step.
Normalized water permeability (NWP) is perhaps the most commonly used performance parameter for monitoring the cleanliness of a UF/DF membrane. NWP uses water to measure the permeability of a membrane , and it allows for a comparison of pre- and post-use membrane cleanliness. Ideally, NWP measurement should be performed after every reuse in a lifespan study.