Equipment Cleaning Validation Within a Multi-Product Manufacturing Facility
Currently, there are multiple publications, as well as guidelines from regulatory agencies thatmake the critical process of equipment cleaning validation easier. These sources provide in-depthinformation for the validation specialist, making the development and implementation of a robustcleaning validation program possible within any particular facility developing or manufacturingparenteral, biological, or sterile ophthalmic products.Extremely important, specific, and above all, mandatory, are the requirements established byregulatory agencies such as the US Food and Drug Administration (FDA), the EuropeanMedicinal Evaluation Agency (EMEA), Australia's Therapeutic Goods Administration (TGA),etc. For example, the 2004 Code of Federal Regulations (CFR) Title 21, Volume 4, Section211.67, states:"Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals toprevent malfunctions or contamination that would alter the safety, identity, strength, quality orpurity of the drug product beyond the official or other established requirements."Additionally, Section 211.182 requires that cleaning procedures must be documentedappropriately, and that a cleaning and use log should be established.This article provides the reader with cleaning validation information enhanced by the author'sthirteen years of hands-on experience working in equipment cleaning validation.
This article focuses on manual cleaning procedures because these are considered the worst-casescenario. It applies to parenterals, ophthalmic, and biologic presentations and is intended to coverequipment validation for raw materials, contaminants, cleaning agents, as well as the control of potential microbial contaminants associated with those products.The flowchart in Figure 1 graphically shows the different aspects that should be considered whendeveloping a cleaning validation program. Understanding each aspect of the process, therelationships among these actions, and the sequence in which they should take place will makethe development of a cleaning validation program a successful experience.
After all applicable cleaning information sources and regulatory guidelines have been consulted,the first item to consider when establishing a cleaning validation program is the raw material andfinal product flow. By following the flow of the product, one can identify the equipment thatcomes in contact with it, such as utensils (scoops, spatulas, funnels, pipettes, etc.), tanks, filterhousings, pressure vessels, syringes, and others. Equipment such as this is considered criticalequipment because it comes in direct contact with the product.