CLEANING VALIDATION SAMPLING PROCEDURE

CLEANING VALIDATION

SAMPLING PROCEDURE

The cleaning validation is to verify the effectiveness of the cleaning procedure for removal of product residues, preservatives, excipients and cleaning agents so that the analytical monitoring may be reduced to a minimum in the routine phase. In addition one need to ensure there is no risk associated with cross contamination of active ingredients. Cleaning validation is intended to address special consideration and issues pertaining to validation cleaning procedures for equipment used in the manufactured of pharmaceutical products, radiopharmaceuticals, and biological drugs. The document is also intended to establish inspection consistency and uniformity with respect to equipment cleaning procedures.

SAMPLING PROCEDURE

In order to evaluate a cleaning method it is necessary to sample the product contact surfaces of the equipment and establish the level of residuals present.

i) Swabs and Wipes Method

Swabbing is the most widely used sampling technique. Swabs may be saturated with solvent such as water or alcohol, facilitating the solubilzation and physical removal of surface residues.

Advantages

 Dissolves and physically remove sample.

 Adequate to a wide variety of surfaces

 Economical and widely available.

 Allows sampling of a defined area.

Limitations

 An invasive technique that may introduce fibers.

 Results may be technique dependent.

 Swab material and design may inhibit recovery and specificity of the method.

 Evaluation of large, complex and hard-toreach areas difficult (e.g. crevices, pipes,     valves, large vessels). In obtaining rinse samples, location, timing and volume are important considerations.

ii) Rinse Method Advantages

 Adaptable to online monitoring.

 Easy to sample and non-intrusive.

 Allows sampling of a large surface area.

 Allows sampling of porous surfaces.

                                                                     

Limitations

 Residues may not be homogeneously distributed.

 Inability to detect location of residues.

 Rinse volume is critical to ensure accurate interpretation of results.

iii) Coupon sampling

Coupons of the same materials of construction as the item to be cleaned can be affixed to the equipment, spiked with the product, subject to the cleaning procedures and then submitted to the laboratory for direct analysis and recovery studies.

Advantages

 Allows for direct surface sampling.

 Useful in cleaning method development.

 Reduced variability in recovery.

 Useful in evaluation of equipment materials of construction.

Limitations

Coupon may not be representative of equipment

contamination or cleaning as it is separate from

primarily surface.

 Invasive

 Might interfere with the cleaning process.

iv) Solvent Sampling

This technique uses a solvent not normally employed in the cleaning process to maximize

recovery residues.

Advantages

 Commonly used in bulk chemical facilities

 Applicable for actives, cleaning agents, excipients

 Less technique dependent than swabs.

 Usually affords more analytical specificity, less recovery loss than swabs. Allows sampling of a larger surface area.

 Allows sampling of porous and delicate surface

 Maximizes recovery to rinse.

Limitations

 May require operator protection and other safety and environmental protection

measures.

 May require more than one sampling for broad spectrum analysis.

 Reduced physical sampling of the surface.

 May be difficult to accurately define the controlled area sampled, therefore usually used for rinsing an entire piece of equipment such as a vessel.

 May require the removal of solvent prior to equipment use for production.

v) Placebo and Product Sampling

Placebo sampling can be used to detects residues on equipment thorough the processing of a place to batch subsequent to the cleaning process. Product sampling is similar to placebo sampling except that it uses actual product.

Advantages

 Points of product contact identical for the batch two batches

 Applicable for hard to reach surfaces.

 Require no additional sampling steps.

Limitations

 Difficult to determine recovery

 Lowers analytical specificity and inhibits detectability

 Residues may not be homogenously distributed.

 No direct measurement of residues on product contact surfaces.