Cleaning Validation is a procedure for verifying the state of cleanliness of a facility and equipment so that product contamination does not occur. This validation procedure must be properly documented to demonstrate that Good Manufacturing Practices (GMP) for finished pharmaceutical products have been properly performed.<\/span><\/p>\n Types of contamination can be divided into three main macrocategories:<\/span><\/p>\n Cleaning Validation follows three main stages:<\/span><\/p>\n Regarding Cleaning Validation, all major Regulators and International Organizations operating in the health and pharmaceutical fields have expressed their views. Below are the guidelines from three of the major international organizations that have been dealing with the issue.<\/span><\/p>\n Within Title 21 of the CFR (Code of Federal Regulation) updated 10\/26\/2022, FDA defines its guidelines related to Cleaning Validation in summary as follows:<\/span><\/p>\n “Equipment and utensils must be cleaned, maintained, and, depending on the nature of the drug, sanitized and\/or sterilized at appropriate intervals to prevent malfunction or contamination that would alter the safety, identity, strength, quality, or purity of the drug produced beyond official requirements or stability.”<\/span><\/p>\n In addition,<\/span><\/p>\n “Procedures shall be established and followed for the cleaning and maintenance of equipment, including tools, used in the manufacture, processing, packaging or holding of a drug product.”<\/span><\/p>\n And finally,<\/span><\/p>\n “Maintenance, cleaning, sanitation, and inspection records must be maintained.”<\/span><\/p>\n In addition to Title 21, FDA has issued other industry guidance documents on:<\/span><\/p>\n Full details on these can be found on this page:<\/b> https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?CFRPart=211<\/span><\/a><\/p>\n Within Title 21, noteworthy is Section 211.68 regarding automatic, mechanical and electronic equipment. The Code of Federal Regulations states, in fact, that:<\/span><\/p>\n “Automatic, mechanical, or electronic equipment or other types of equipment, including computers or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packaging, and warehousing of a pharmaceutical product. If such equipment is used in this manner, it must be regularly calibrated, inspected or verified according to a program designed to ensure adequate performance. Written records of such calibration checks and inspections shall be maintained.”<\/span><\/p>\n For more information please visit the following link:<\/b> https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=211.68<\/a>\u00ca<\/span><\/p>\n What is clear from Title 21 of the U.S. Code of Federal Regulations is the strong clear invitation to use, in the manufacture and storage of pharmaceutical products<\/span>, technological equipment, designed to the highest standards and conforming to the guidelines,<\/b> to be coupled with organized and standardized procedures to prevent the presence of residues and bacteria within ready-to-market pharmaceutical products. <\/span>For the FDA, therefore, validation of cleaning procedures and verification based on scientific facts play a decisive role in preventing cross-contamination.<\/b><\/p>\n EMA is leading the way in establishing guidelines on Cleaning Validation. The EMA, within the “Guidelines for the Establishment of Health-Based Exposure Limits for the Identification of Risks in the Production of Various Medicinal Products in Shared Facilities” – in force since June 2015, has made it mandatory to establish <\/span>health-based exposure limits (HBELs)<\/b> for all pharmaceuticals, based on the permitted daily exposure values.<\/span><\/p>\n Therefore the establishment of the guidelines was followed by EMA’s publication in 2019 of a comprehensive section of 14 specific questions and answers on the topic including:<\/span><\/p>\n The message from EMA is clear: “HBELs must be established for all medicines. Toxicological or pharmacological data, on which the calculation of HBELs is based, require periodic reassessment throughout the life cycle of a product.”<\/span><\/p>\n To view the full guideline document, please visit this link:<\/b> https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-setting-health-based-exposure-limits-use-risk-identification-manufacture-different_en.pdf<\/span><\/a><\/p>\n If, on the other hand, you would like to learn more about the document published by EMA with Q&As, click here:<\/b> https:\/\/www.ema.europa.eu\/en\/documents\/other\/questions-answers-implementation-risk-based-prevention-cross-contamination-production-guideline_en.pdf<\/span><\/a><\/p>\n WHO’s Cleaning Validation guidelines are similar to those of the FDA.<\/span><\/p>\n Within WHO’s “Technical Report Series 1019 of 2019,” Annex 3 is devoted entirely to <\/span>good manufacturing practices and validation guidelines<\/b>. WHO specifies that “Validation is an essential part of good practices, including good manufacturing practices (GMPs) and good clinical practices (GCPs)” and specifies that validation should be applied throughout the entire life cycle of; a product, process, method, system or equipment.<\/span><\/p>\n\n
\n
Cleaning Validation: guidelines from leading regulators and organizations<\/b><\/h1>\n
USFDA – United States Food and Drug Administration<\/b><\/h2>\n
\n
EMA – European Medicines Agency<\/b><\/h2>\n
\n
WHO – World Health Organization<\/b><\/h2>\n