WHAT IS CLEANING VALIDATION?
The U.S. Food and Drug Administration (FDA) issued its Guide to Inspections—Validation of Cleaning Process¹ in 1993. Since that time, the protocols surrounding cleaning processes in pharmaceutical manufacturing environments and sampling and filling suites have received increased attention.^2,3 The primary regulatory concern driving the need for cleaning validation is crosscontamination of the desired drug substance either by other active pharmaceutical ingredients (API) from previous batch runs or by residues from the cleaning agents used.

Cross-contamination with extraneous residues of any kind presents a safety risk to patients consuming the drug product. It threatens to alter the strength, chemical identity, and integrity of the drug substance and formulation. Therefore, the equipment and work environments involved in drug manufacturing processes must be cleaned at regular, prescribed intervals to prevent the possibility of such cross-contamination. These cleaning protocols must be validated in order to provide assurance that they do, in fact, serve their purpose—to clean the surfaces to a level that avoids the possibility of cross-contamination.

In recent years, increased emphasis has been placed on the development of validated and robust cleaning protocols given the concerns over the safety of our drug supply. Growth in the levels of outsourcing and off-shoring of pharmaceutical manufacturing has heightened the FDA’s concern over cleaning processes. Inadequate documentation, training, and validation of cleaning processes rank high among the four most often cited problems in Form 483 and warning letters that have been issued by the U.S. FDA.⁴

WHY SWABBING?
In a typical pharmaceutical manufacturing environment, cleaning might be performed by using 70% isopropyl alcohol (IPA) and/or other chemicals, detergents, and sanitizing agents in order to remove residues from the previous batch run. The areas thus cleaned must now be sampled adequately and appropriately in order to validate the cleaning protocol.

Swabbing and rinsing are the two most common techniques used for sampling of such cleaned surfaces. Swabbing is a direct surface sampling method, while rinsing is an indirect method. In practice, physical access to surfaces and parts of equipment to be cleaned tends to drive the choice of sampling method. For example, swabbing would work particularly well in more restricted work areas such as isolators, hoods, and accessible corners of equipment, while rinsing would work best in pipes and longer tubes. In general, a combination of both is most desirable in order to accomplish the most comprehensive coverage of surfaces to be cleaned.