1、Designation:E1298 06Standard Guide forDetermination of Purity,Impurities,and Contaminants inBiological Drug Products1This standard is issued under the fixed designation E1298;the number immediately following the designation indicates the year oforiginal adoption or,in the case of revision,the year o
2、f last revision.A number in parentheses indicates the year of last reapproval.Asuperscript epsilon()indicates an editorial change since the last revision or reapproval.INTRODUCTIONThe purity of biological drug products historically has been significantly lower than that of otherpharmaceutical drug p
3、roducts.This is a consequence of the structural complexity of biological drugproducts as well as the fact that,until recently,these products were obtained only with great difficultyand at high cost from natural sources such as human or animal serum or tissue.Although many ofthese products were of lo
4、w purity,long-term use in humans proved their safety and efficacy.Thedevelopment of recombinant DNA(rDNA)technology and the parallel development of sophisticatedpreparatory,analytical,and immunological methods,have resulted in the ability to produce high puritybiological drug products.It should be r
5、ecognized that the standards for purity of rDNA-derived drugsare comparable to those established for United States Pharmacopeia(USP)-quality drug substances.For example,the purity of an rDNA-derived drug substance may exceed 97%and impurities,(seeSection 4)such as host cell proteins are separately q
6、uantitated in the parts per million range(viaimmunoassay).1.Scope1.1 This guide covers the concepts of purity,impurity,andcontamination in biological drug products.1.2 This guide suggests methods for determination of im-purities and contaminants in such products.1.3 This guide is arranged as follows
7、:SectionTerminology2Significance and Use3Purity4General Considerations4.1Estimation of Purity4.2Impurities5General Considerations5.1Major and Minor5.2Nature and Consequences of5.3Contaminants6General Considerations6.1Effects of contaminants5.2Methods for Determining Impurities and Contaminants71.4 T
8、his standard does not purport to address all of thesafety concerns,if any,associated with its use.It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2.Terminology2.1 Defini
9、tions:2.1.1 contaminantsall adventitious substances or micro-organisms present in raw materials,bulk drugs,or finalproducts.2.1.2 deleterious impuritiesimpurities that might be ahealth or safety concern,particularly with respect to toxicity,carcinogenicity,or immunogenicity.Deleterious impuritiesmus
10、t be controlled and their levels determined using suitableanalytical methods.2.1.3 impurities,of a biological drug productall process-related(nonadventitious)substances present in the raw mate-rials,bulk drug,or final drug product that are not considered tobe the active material,additives,or excipie
11、nts.2.1.4 innocuous impuritiesimpurities that are not a healthor safety concern in the product.The route of administration ofthe drug may be a significant criterion in the determination ofwhether an impurity is innocuous.2.1.5 purity,of a biological drug productthe measure ofthe biologically active
12、drug in relation to the total substances(not including additives)present in the drug product,usuallyexpressed on a percentage basis.1This guide is under the jurisdiction of ASTM Committee E55 on Manufactureof Pharmaceutical Products and is the direct responsibility of Subcommittee E55.04on General B
13、iopharmaceutical Standards.Current edition approved Nov.1,2006.Published November 2006.Originallyapproved in 1998.last previous edition approved in 2000 as E1298 98(2000).DOI:10.1520/E1298-06.1Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959,United State
14、s.Copyright ASTM International Provided by IHS under license with ASTM Licensee=Ohio State University/5967164005,User=ahmadi,rozitaNot for Resale,03/26/2012 04:35:38 MDTNo reproduction or networking permitted without license from IHS-,-,-3.Significance and Use3.1 This guide suggests analytical metho
15、ds generally ap-plied within the pharmaceutical industry to identify and quan-titate the level of impurities and contaminants present in thepreparation of a biological drug product.These methods arenot intended to be all-inclusive.The methods used by anindividual manufacturer must be specific to the
16、 product andprocess of production.4.Purity4.1 General ConsiderationsNumerous considerations areinvolved in determining purity acceptability criteria,and thesecriteria are ultimately determined on a case-by-case basis.Ineach individual case,the risk-to-benefit ratio must be evaluatedin determining an acceptable level of purity and the acceptabletypes of impurities of any new drug product.For example,thesame purity requirements are not necessarily applied to avaccine,which may be administered in o