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1、USP-中英对照-USP-NF- 作者： 日期：ELEMENTAL IMPURITIESLIMITSINTRODUCTIONThis general chapter specifies limits for the amounts of elemental impurities in drug products. Elemental impurities include catalysts and environmental contaminants that may be present in drug substances, excipients, or drug products. Th
2、ese impurities may occur naturally, be added intentionally, or be introduced inadvertently (e.g., by interactions with processing equipment and the container closure system). When elemental impurities are known to be present, have been added, or have the potential for introduction, assurance of comp
3、liance to the specified levels is required. A risk-based control strategy may be appropriate when analysts determine how to assure compliance with this standard. Due to the ubiquitous nature of arsenic, cadmium, lead, and mercuy, they (at the minimum) must be considered in the risk-based control str
4、ategy assessment. Regardless of the approach used, compliance with the limits specified is required for all drug products unless otherwise specified in an individual monograph or excluded in paragraph three of this introduction.The drug products containing purified proteins and polypeptides (includi
5、ng proteins and polypeptides produced from recombinant or non-recombinant origins), their derivatives, and products of which they are components (e.g., conjugates) are within the scope of this chapter, as are drug products containing synthetically produced polypeptides, polynucleotides, and oligosac
6、charides.This chapter does not apply to radiopharmaceuticals, vaccines, cell metabolites, DNA products, allergenic extracts, cells, whole blood, cellular blood components or blood derivatives including plasma and plasma derivatives, dialysate solutions not intended for systemic circulation, and elem
7、ents that are intentionally included in the drug product for therapeutic benefit. This chapter does not apply to products based on genes (gene therapy), cells (cell therapy), and tissue (tissue engineering).The limits presented in this chapter do not apply to excipients and drug substances, except w
8、here specified in this chapter or in the individual monographs. However, elemental impurity levels present in drug substances and excipients must be known, and reported documented, and made available upon request.This chapter does not apply to The limits indicated in this chapter are not required fo
9、r articles intended only for veterinary use and conventional vaccines. Requirements listed in this chapter also do not apply to total parenteral nutritions (TPNs) and dialysates. Dietary supplements and their ingredients are addressed in Elemental Contaminants in Dietary Supplements .SPECIATIONThe d
10、etermination of the oxidation state, organic complex, or combination is termed speciation. Each of the elemental impurities has the potential to be present in differing oxidation or complexation states. However, arsenic and mercury are of particular concern because of the differing toxicities of the
11、ir inorganic and complexed organic forms.The arsenic limits are based on the inorganic (most toxic) form. Arsenic can be measured using a total-arsenic procedure under the assumption that all arsenic contained in the material under test is in the inorganic form. Where the limit is exceeded using a t
12、otal-arsenic procedure, it may be possible to show via a procedure that quantifies the different forms that the inorganic form meets the specification.The mercury limits are based upon the inorganic (2+) oxidation state. The methyl mercury form (most toxic) is rarely an issue for pharmaceuticals. Th
13、us, the limit was established assuming the most common (mercuric) inorganic form. Limits for articles that have the potential to contain methyl mercury (e.g., materials derived from fish) are to be provided in the monograph.ROUTES OF EXPOSUREThe toxicity of an elemental impurity is related to its ex
14、tent of exposure (bioavailability). The extent of exposure has been determined for each of the elemental impurities of interest for three routes of administration: oral, parenteral, and inhalational. These limits are based on chronic exposure. The other two routes of administration, mucosal and topi
15、cal, are considered to be the same as oral for the purpose of this standard, and the PDEs described in Table 1 would apply to these products. To account for the potential application of topical products to injured or broken skin, topical product permissible daily exposures (PDEs) will be the same as
16、 oral Table 1, except as indicated in the individual monograph. Mucosal will also use oral PDEs, except where otherwise stated in the individual monograph. Consider the oral permissible daily exposures (PDEs) in Table 1, as a starting point in developing specific PDEs for other routes of administratio
