Application Note: Real time, low flow, pharmaceutical soil cleanability profiling with TOC and conductivity

Designing a robust cleaning process for pharmaceutical drug manufacturing is critical to successful cleaning validation and verification.

Historically, cleaning process design for pharmaceutical manufacturing was focused on reducing active pharmaceutical ingredients (API) with the highest potency or toxicity down to or below the maximum allowable carryover (MAC) limits. The Food and Drug Administration (FDA) as well as industry experts have placed an increasing emphasis on reducing risk and demonstrating process control and process understanding for validated cleaning processes. The concept of total cleanability and master soil identification is an emerging area of interest for risk reduction when developing a validated cleaning process.¹

A traditional total cleanability study can be achieved by isolating each potential soil and, under worst case cleaning conditions (e.g. concentration, temperature, etc.) ranking all soils based on time until clean. Using the time until clean metric, a master soil is identified and the cleaning process is optimised around reducing the master soil. This method assumes that by reducing the master soil, all other soils will be reduced even further. Traditionally, these cleanability studies are performed using visual clean as the qualitative metric for ranking.² The studies can be time and resource intensive, do not provide adequate sample frequency, and rely on subjective rankings such as visually clean.