ASTM E1298-06
(Guide)Standard Guide for Determination of Purity, Impurities, and Contaminants in Biological Drug Products (Withdrawn 2014)
Standard Guide for Determination of Purity, Impurities, and Contaminants in Biological Drug Products (Withdrawn 2014)
SIGNIFICANCE AND USE
This guide suggests analytical methods generally applied within the pharmaceutical industry to identify and quantitate the level of impurities and contaminants present in the preparation of a biological drug product. These methods are not intended to be all-inclusive. The methods used by an individual manufacturer must be specific to the product and process of production.
SCOPE
1.1 This guide covers the concepts of purity, impurity, and contamination in biological drug products.
1.2 This guide suggests methods for determination of impurities and contaminants in such products.
1.3 This guide is arranged as follows:
1.4 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 and health practices and determine the applicability of regulatory limitations prior to use.
WITHDRAWN RATIONALE
This guide covers the concepts of purity, impurity, and contamination in biological drug products.
Formerly under the jurisdiction of Committee E55 on Manufacture of Pharmaceutical Products, this guide was withdrawn in August 2014. This standard was withdrawn without replacement due to its limited use by the industry.
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NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: E1298 − 06
StandardGuide for
Determination of Purity, Impurities, and Contaminants in
1
Biological Drug Products
This standard is issued under the fixed designation E1298; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
INTRODUCTION
The purity of biological drug products historically has been significantly lower than that of other
pharmaceutical drug products. This is a consequence of the structural complexity of biological drug
products as well as the fact that, until recently, these products were obtained only with great difficulty
and at high cost from natural sources such as human or animal serum or tissue. Although many of
these products were of low purity, long-term use in humans proved their safety and efficacy. The
development of recombinant DNA (rDNA) technology and the parallel development of sophisticated
preparatory,analytical,andimmunologicalmethods,haveresultedintheabilitytoproducehighpurity
biological drug products. It should be recognized that the standards for purity of rDNA-derived drugs
are 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, (see
Section 4) such as host cell proteins are separately quantitated in the parts per million range (via
immunoassay).
1. Scope responsibility of the user of this standard to establish appro-
priate safety and health practices and determine the applica-
1.1 This guide covers the concepts of purity, impurity, and
bility of regulatory limitations prior to use.
contamination in biological drug products.
1.2 This guide suggests methods for determination of im-
2. Terminology
purities and contaminants in such products.
2.1 Definitions:
1.3 This guide is arranged as follows:
2.1.1 contaminants—all adventitious substances or microor-
Section ganisms present in raw materials, bulk drugs, or final products.
Terminology 2
2.1.2 deleterious impurities—impurities that might be a
Significance and Use 3
Purity 4 health or safety concern, particularly with respect to toxicity,
General Considerations 4.1
carcinogenicity, or immunogenicity. Deleterious impurities
Estimation of Purity 4.2
must be controlled and their levels determined using suitable
Impurities 5
General Considerations 5.1 analytical methods.
Major and Minor 5.2
2.1.3 impurities, of a biological drug product—all process-
Nature and Consequences of 5.3
Contaminants 6 related (nonadventitious) substances present in the raw
General Considerations 6.1
materials, bulk drug, or final drug product that are not
Effects of contaminants 5.2
considered to be the active material, additives, or excipients.
Methods for Determining Impurities and Contaminants 7
2.1.4 innocuous impurities—impurities that are not a health
1.4 This standard does not purport to address all of the
or safety concern in the product.The route of administration of
safety concerns, if any, associated with its use. It is the
the drug may be a significant criterion in the determination of
whether an impurity is innocuous.
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This guide is under the jurisdiction of ASTM Committee E55 on Manufacture
of Pharmaceutical Products and is the direct responsibility of Subcommittee E55.04
2.1.5 purity, of a biological drug product—the measure of
on General Biopharmaceutical Standards.
the biologically active drug in relation to the total substances
Current edition approved Nov. 1, 2006. Published November 2006. Originally
(not including additives) present in the drug product, usually
approved in 1998. last previous edition approved in 2000 as E1298 – 98 (2000).
DOI: 10.1520/E1298-06. expressed on a percentage basis.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
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E1298 − 06
TABLE 1 Methods for Determination of Impurities and
3. Significance and Use
Contaminants
3.1 This guide suggests analytical methods generally ap-
Common Impurities
Detection Method
plied within the pharmaceutical industry to identify and quan-
or Contaminants
titate the level of impurities and contaminants present in the A
Endotoxin LAL, rabbit pyrogen,
immunoassays, Masspectrometry
preparation of a biological drug product. These methods are
not intended to be all-inclusive. The methods used by an
B
Host Cell Proteins SDS-PAGE, immunoassays
individual manufacturer must be specific to the product and
C
Other Protein Impurities SDS-PAGE, HPLC, immunoassays
process of production.
Nucleic Acids DNA hybridization, UV spect
...
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