Cleaning Validation Lifecycle

Study Notes

Cleaning Validation Lifecycle - Stage 1

The first stage of the cleaning validation lifecycle involves characterizing the product and determining the worst-case soiling material.
This stage aims to identify key factors affecting cleaning and establish a robust cleaning process.
Ishikawa analysis is used to identify potential parameters influencing the cleaning process.
Definitive screening design helps to identify critical factors affecting the hardest-to-clean product.
Design of Experiments (DoE) is utilized to optimize cleaning process parameters for the hardest-to-clean product.
Product Characterization Assessment involves evaluating various aspects of the product, including its chemical composition, toxicity, solubility, and cleanability.
TACT (Time, Action, Concentration/Chemistry, Temperature) represents critical process parameters influencing cleaning effectiveness.
Active cleaning limits help define the acceptable level of contamination based on factors like batch size, potency, contact area, and toxicity.
The worst-case soiling material accounts for residues like active ingredients, decomposition products, microbial contamination, endotoxins, sanitizing agents, lubricants, environmental dust, and residual rinse water.
Designing the cleaning process considers the equipment being cleaned, the types of soils to be removed, cleaning methods, agents, mechanisms, parameters, and residue limits.
Soil types include actives, excipients, process materials, bioburden, and endotoxins.
Freshly deposited, dried, baked-on, and compacted soils are considered during cleanability evaluation.
Cleaning efficiency factors include cleaning solution temperature, cleaning agent concentration, solution contact time, and external energy.
Cleaning methods range from fixed CIP and portable CIP to parts washers, ultrasonic cleaning, and manual techniques (soak, brush, wipe, spray).
Residue limits represent the acceptable level of remaining residues after cleaning.
Residue limits are determined considering what residues need to be removed and how clean is clean.
Analytical methods used to measure residues can influence the cleaning process.
Residue-specific assays are unique to specific analytes, more expensive, and require validation for cleaning applications.
Residue non-specific assays are less expensive, have broader applications, and provide high precision but have lower specificity.
Rinse water testing provides a relatively easy and indirect measure of cleanliness using product-specific or non-specific assays.
Surface testing directly measures cleanliness through visual inspection and swabbing, and is more challenging to perform.
Sampling and testing methods include solvent rinse, water rinse, visual inspection, swabbing, and contact plates for microbiological analysis.
Visual detection can detect many compounds down to low levels.