ASTM E3418-23 PDF

SIGNIFICANCE AND USE 4.1 Pharmaceutical Discussion: 4.1.1 The origins for the calculation of cleaning validation limits for pharmaceuticals date back to the 1980's with the publication of an article in 1984, that stated that "limits must be safe and acceptable and in line with residual limits set for various substances in foods" (7). A second article in 1989 expanded upon these ideas adding that an "effect threshold" should be established in collaboration with toxicology and medical authorities (or alternatively, an appropriate safety factor. For example, 10× or 100× could be superimposed) and finally that limits for surface residue levels could then be calculated based on a smallest batch size/maximum dose combination. This article further mentioned that this calculation leads to many limits that could be verified through visual inspection (8). A third article in 1993, proposed the use of a combination of limits suggesting that carryover of product residues needed to meet these three criteria: (1) No more than 0.001 dose of any product will appear in the maximum daily dose of another product, (2) No more than 10 ppm of a product will appear in another product, and (3) No quantity of residue will be visible on the equipment after cleaning procedures are performed (9). 4.1.2 In 1993, United States Food and Drug Administration (USFDA) issued a guide for its inspectors requiring that "the basis for any limits must be scientifically justifiable" (6). In 1996, USFDA proposed that, in addition to penicillin, certain "classes" of compounds would also need to be manufactured in dedicated facilities and would expect manufacturers to identify any drugs that present the risk of cross-contamination and to implement measures necessary to eliminate that risk (10). Otherwise, nothing short of dedicated facilities or equipment would be sufficient. In 2005, the European Medicines Agency (EMA) similarly announced that it would require dedicated facilities for certain medicines in addition t... SCOPE 1.1 This practice provides procedures for calculating safe and scientifically justifiable limits of residues for use in cleaning validation studies of pharmaceutical/biopharmaceutical/medical device manufacturing equipment surfaces and medical device surfaces. 1.2 The procedures in this standard practice for calculating safe limits of chemical residues are based on Guide E3219. 1.3 This practice applies to pharmaceuticals (including active pharmaceutical ingredients (APIs); dosage forms; and over-the-counter, veterinary, biologics, and clinical supplies) and medical devices following all manufacturing and cleaning. This practice is also applicable to other health, cosmetics, and consumer products. 1.4 This practice applies to all types of chemical residues (including APIs; intermediates, cleaning agents, processing aids, machining oils, etc.) that could remain on manufacturing equipment surfaces or on medical devices that have undergone all manufacturing steps including cleaning. This practice does not cover extractables and leachables (see ISO 10993-17). 1.5 This practice applies to microbiological residues that may be present on manufacturing equipment surfaces or on medical devices that have undergone all manufacturing steps including cleaning and does not cover disinfection or sterilization. 1.6 Exclusions—Medical devices that do not make patient contact; non-product contact surfaces (which are discussed in other existing guides: Ref (1)2, PDA TR 29, USP , Guide E2614, ISO 14698, and ISO 14937). 1.7 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.8 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limit...