Thus, it is unnecessary to name repetitively the revised Reference Standards in the general index to the Supplement. General Chapters 1274 á1724ñ Semisolid Drug Products / General Information USP … Where drying in vacuum over a desiccant is directed in the individual monograph, a vacuum desiccator or a vacuum drying pistol, or other suitable vacuum drying apparatus, is to be used. Compliance may be determined also by the use of alternative methods, chosen for advantages in accuracy, sensitivity, precision, selectivity, or adaptability to automation or computerized data reduction or in other special circumstances. Since some USP Reference Standards are standardized in terms of the corresponding International Standards, the relevant USP Units and the International Units of potency are generally identical. If so, it is identified in the second column. The list that follows presents the instructions for the proper use and storage of each required USP Reference Standard. 2.10. In the performance of assay or test procedures, not fewer than the specified number of dosage units should be taken for analysis. clinical studies is described in USP general chapter Immunogenicity Assays—Design and Validation of Immunoassays to Detect An-ti-Drug Antibodies á1106ñ. In stating the appropriate quantities to be taken for assays and tests, the use of the word “about” indicates a quantity within 10% of the specified weight or volume. The manufacturer's release specifications, and compliance with good manufacturing practices generally, are developed and followed to ensure that the article will indeed comply with compendial standards until its expiration date, when stored as directed. ✦for dosage forms administered orally. This chapter defines the terms and procedures used in chromatography and provides general information. While one of the primary objectives of the Pharmacopeia is to assure the user of official articles of their identity, strength, quality, and purity, it is manifestly impossible to include in each monograph a test for every impurity, contaminant, or adulterant that might be present, including microbial contamination. Compendial standards define what is an acceptable article and give test procedures that demonstrate that the article is in compliance. Scope Indicator and Test Papers Indicator and Test Papers Introduction, 5747 General Tests and Assays Buffer Solutions Buffer Solutions Introduction, 5748 3. The concentration of test microorganisms that is added to the product (Categories 1, 2, and 3) are such that the final concentration of the test preparation after inoculation is between 1 × 10 5 and 1 × 10 6 cfu per mL of the statistics at least at the level of USP general chapter Analyti-sample suitability, results for that sample are reported cal Data—Interpretation and Treatment 〈1010〉 and with lin- as “Fails Sample Suitability.” Relative potencies for ear regression. USP will then address the information in the individual monograph. The quantitative methods were successfully transferred/verified to ensure accurate and reliable Items capable of equal or better performance may be used if these characteristics have been validated. The test is often conducted with a group of 6 or 12 cells per test run. 2002]. General Chapters Butylated Hydroxytoluene (new), 2341 Copper Sulfate Pentahydrate (new), 2348 Cupric Nitrate, 2348 1,1-Cyclobutanedicarboxylic Acid (new), 2349 General Tests and Assays Hydroxypropyl Cellulose (new), 2364 Isonicotinic Acid, 2366 ... USP Reference Standards ASSAY The portion of the powdered tablets taken for assay is representative of the whole Tablets and is, in turn, weighed accurately. Antibiotic reference standards distributed by the USPC have been designated by the FDA as identical to FDA working standards under the FDA procedures. Such procedure shall be submitted to the USP for inclusion in the relevant individual monograph. It is the responsibility of each analyst to ascertain that his particular supply of USP Reference Standard is current. 2. The same tolerance applies to specified dimensions. The ratio of a given dose of the Standard, in µg or in USP Units, to the corresponding dose of the Unknown, measured as specified in the monograph, is designated uniformly by R. The closer the agreement between this original assumption and the result of the assay, the more precise is the calculated potency. responsibility of that manufacturer to notify USP of the identity and level of the solvent, and the appropriate test procedure. Every compendial article in commerce shall be so constituted that when examined in accordance with these assay and test procedures, it meets all the requirements in the monograph defining it. 10 the US Pharmacopeia (USP). From the information available for the preparation to be assayed (the “Unknown”), assign to it an assumed potency per unit weight or volume, and on this assumption prepare on the day of the assay a stock solution and test dilution as specified for each antibiotic but with the same final diluent as used for the USP Reference Standard. In order to obtain solutions having concentrations that are adaptable to the working range of the instrument being used, solutions of proportionately higher or lower concentrations may be prepared according to the solvents and proportions thereof that are specified for the procedure. According to Section 501 of the Federal Food, Drug, and Cosmetic Act, assays and specifications in monographs of the United States Pharmacopeia and the National Formulary constitute legal standards. The USP Reference Standards Laboratory (see, Reference Standards are specifically required in many Pharmacopeial assays and tests and are provided solely for such use; suitability for other nonofficial application(s) rests with the purchaser. The presence of any unlabeled impurity in an official substance is a variance from the standard if the content is 0.1% or greater. See also. Where the use of a centrifuge is indicated, unless otherwise specified, the directions are predicated upon the use of apparatus having an effective radius of about 20 cm (8 inches) and driven at a speed sufficient to clarify the supernatant layer within 15 minutes. This chapter provides guidance and procedures used for characterization of biotechnology-derived articles. strength, quality, and purity of an article are determined by Unless otherwise directed in the test or assay in the individual monograph or in a general chapter, USP Reference Standards are to be dried before use, or used without prior drying, specifically in accordance with the instructions given in the chapter USP Reference Standards 11, and on the label of the Reference Standard. The alphabetical list that follows constitutes an index of all revisions to this chapter. 108 Chapter 5: Identification, Assay and Related Substances Introduction The BP, Ph.Int. The term “transfer” is used generally to specify a quantitative manipulation. Where special storage conditions are necessary, directions are given on the label. Publish Omission of General Chapter <231> o Published in USP 38–NF 33 with an statistics at least at the level of USP general chapter Analyti-sample suitability, results for that sample are reported cal Data—Interpretation and Treatment 〈1010〉 and with lin- as “Fails Sample Suitability.” Relative potencies for ear regression. 98mm to 106mm; ✦for a nominal capacity of 2 L, the Generally, Reference Standards should be stored in their original stoppered containers away from heat and protected from light. Chapter 51 describes in detail the USP method for preservative efficacy testing, sometimes called "preservative challenge testing." The average of 6 slopes for each test and reference product is a measure of the drug release rate from the dosage form. Proportionately larger or smaller quantities than the specified weights and volumes of assay or test substances and Reference Standards may be taken, provided the measurement is made with at least equivalent accuracy and provided that any subsequent steps, such as dilutions, are adjusted accordingly to yield concentrations equivalent to those specified and are made in such manner as to provide at least equivalent accuracy. Sulfate— Dissolve the specified quantity of the substance under test in 30 to 40 mL of water, or, where the substance is already in solution, add water to make a total volume of 30 to 40 mL, and, if necessary, neutralize the solution with hydrochloric acid to litmus. In performing the assay or test procedures in this Pharmacopeia, it is expected that safe laboratory practices will be followed. These additional substances fall into three groups: (1) former USP and NF Reference Standards, not required in the current. Such alternative or automated procedures or methods shall be validated. In such cases, measurements are made on preparations of both the test specimen and the Reference Standard. Tests suitable for detecting such occurrences, the presence of which is inconsistent with applicable good manufacturing practice or good pharmaceutical practice, should be employed in addition to the tests provided in the individual monograph. While on the absolute scale viscosity is measured in poises or centipoises, for convenience the kinematic scale, in which the units are stokes and centistokes (1 stoke = 100 centistokes) commonly is used. Originally introduced for the biological assays of. The USP Reference standards section of an individual USP or NF monograph or general chapter names each USP Reference Standard required for assay and test procedures and refers to this chapter for additional information and instructions. The assay with five levels of the Standard … and USP each has a monograph for the analysis of quinine sulfate tablets. Some tests, such as those for. Where an instrument for physical measurement, such as a spectrophotometer, is specified in a test or assay by its distinctive name, another instrument of equivalent or greater sensitivity and accuracy may be used. Neither Reference Standards nor Authentic Substances are intended for use as drugs or as medical devices. The notation “VS” after a specified volumetric solution indicates that such solution is standardized in accordance with directions given in the individual monograph or under. Microbial examination of nonsterile products is performed according to the methods given in the texts on Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62.Acceptance criteria for nonsterile pharmaceutical products based upon the total aerobic microbial count (TAMC) and the total combined yeasts and molds count (TYMC) are given in Tables 1 and 2. Prior to undertaking any assay or procedure described in this Pharmacopeia, the individual should be aware of the hazards associated with the chemicals and the procedures and means of protecting against them. The suitability of a USP Reference Standard for noncompendial application is left up to the user. Soluble Pharmacopeial articles, when brought into solution, may show traces of physical impurities, such as minute fragments of filter paper, fibers, and other particulate matter, unless limited or excluded by definite tests or other specifications in the individual monographs. The result of the assay is then related to the amount of active ingredient per Capsule by multiplying this result by the average weight of Capsule content and dividing by the weight of the portion taken for the assay. Its various sections are interrelated. Data derived from manufacturing. Tests and assays in this Pharmacopeia prescribe operation on a single specimen, that is, the singlet determination, which is the minimum sample on which the attributes of a compendial article should be measured. Thus, when tested from the viewpoint of commercial or regulatory compliance, any specimen tested as directed in the monograph for that article shall comply. HCPs can also have a direct effect on the quality of the product itself. 63 in USP. These standards apply at any time in the life of the article from production to consumption. Where a standardized solution of a specific concentration is called for in a test or an assay, a solution of other normality or molarity may be used, provided allowance is made for the difference in concentration and provided the error of measurement is not increased thereby. Where the use of a pipet is directed for measuring a specimen or an aliquot in conducting a test or an assay, the pipet conforms to the standards set forth under, Expressions such as “25.0 mL” and “25.0 mg,” used with respect to volumetric or gravimetric measurements, indicate that the quantity is to be “accurately measured” or “accurately weighed” within the limits stated under. Identification tests for citrate and phosphate are provided separately under USP general chapter Identification Tests—General 191. These may arise from a change in the source of material or from a change in the processing, or may be introduced from extraneous sources. A medical device, dietary supplement, or ingredient or compo-Each general chapter is assigned a number that appears in angle nent of a medical device or dietary supplement may use the desig-brackets adjacent to the chapter name (e.g., Chromatography nation “USP” or “NF” in conjunction with its official title or else-〈621〉). [DRUG] for Injection—Dry solids that, upon the addi- Tests and Assays tion of suitable vehicles, yield solutions conforming in all respects to the requirements for Injections. In some cases, the previous lot may still be considered official. The USP Reference standards section of an individual USP or NF monograph or general chapter names each USP Reference Standard required for assay and test procedures and refers to this chapter for additional information and instructions. USP publishes endotoxin testing recommendations and acceptance criteria in USP General Chapter <85> Bacterial Endotoxins Test. Reference Standard” may be used, and vice versa. For example, proteolytic HCPs, Publish Omission of General Chapter <231> o Published in USP 38–NF 33 with an Unlike chemical reference standards, Authentic Visual References (AVRs) are not used in chemical analysis. If a manufacturer chooses to use a recombinant factor C-based assay, then method validation should be in accordance with the requirements of USP Chapter, Bacterial Endotoxins Test, as … As an additional service, the USPC distributes several non-commercial reagents required in certain. USP 35 General Requirements / 〈1〉 Injections33 General Chapters General Tests and Assays 1. As a rule, an International Standard for a material of natural origin is discontinued once the substance responsible for its characteristic activity has been isolated, identified, and prepared in such form that it can be completely characterized by chemical and physical means. The WHO program is concerned with reference materials for antibiotics, biologicals, and chemotherapeutic agents. To minimize environmental impact or contact with hazardous materials, apparatus and chemicals specified in Pharmacopeial procedures also may be proportionally changed. A “vacuum desiccator” is one that maintains the low-moisture atmosphere at a reduced pressure of not more than 20 mm of mercury or at the pressure designated in the individual monograph. For example, proteolytic HCPs, The critical characteristics of each lot of specimen selected for the standard are usually determined independently in three or more laboratories. These also are provided under the supervision of the USP Reference Standards Committee. USP Reference Standards are substances selected for their high purity, critical characteristics, and suitability for the intended purpose. USP General Chapter <81> entitled “Antibiotic Potency Assays” provides two (2) method types for determining antibiotic potency: Cylinder-Plate Assay and Turbidimetric Assay. If you would like to learn more about the USP <51> preservative challenge test, you are in the right place! Official Text ble general chapters, and General Notices. The partitioning of chapters to different aspects of 11 biological assays allows both greater focus and clarity and the opportunity to expand on 12 issues. 108 Chapter 5: Identification, Assay and Related Substances Introduction The BP, Ph.Int. To ensure ready access to the latest information, the USPC publishes the Official Catalog of Reference Standards and Authentic Substances, and the lot designations, bimonthly in. and USP each has a monograph for the analysis of quinine sulfate tablets. Similarly, where it is directed in the assay of Capsules to remove, as completely as possible, the contents of not fewer than a given number, usually 20, of the Capsules, it is intended that a counted number of Capsules should be carefully opened and the contents quantitatively removed, combined, mixed, and weighed accurately. Where special drying requirements for Reference Standards are found in specific sections of, Revisions, additions, and deletions of individual USP Reference Standards are listed cumulatively in each Supplement to, Revisions of this chapter are implemented continuously via the. Only sufficient quantity for immediate use should be purchased, and long-term storage should be avoided. Add 1 mL of 3 N hydrochloric acid, 3 mL of barium chloride TS, and sufficient water to make 50 mL. Approval of AVRs for use in a monograph is the decision of the Expert Committee that approves the specific monograph. The USP Reference Standards Committee collaborates closely with the WHO in order to minimize unavoidable differences in the actual units of potency, and in some cases to share in the preparation of a reference standard. Unless otherwise directed in the test or assay in the individual monograph or in a general chapter, USP Reference Standards are to be dried before use, or used without prior drying, specifically in accordance with the instructions given in the chapter USP Reference Standards 11, and on the label of the Reference Standard. The term “concomitantly,” used in such expressions as “concomitantly determine” or “concomitantly measured,” in directions for assays and tests, is intended to denote that the determinations or measurements are to be performed in immediate succession. This Pharmacopeia is not designed to describe such hazards or protective measures. One column identifies the official lot currently being shipped by USPC. The approximate solubilities of Pharmacopeial substances are indicated by the descriptive terms in the accompanying table. The Glass Grains Test, combined with the Surface Glass Test for hydrolytic resistance, determines the type of glass being used in the packaging of pharmaceutical preparations. These general chapters, USP <660> Containers – Glass and EP (3.2.1) Glass Containers for Pharmaceutical Use deal with the Glass Grains Test and the Surface Glass Test. This chapter is harmonized with the corresponding chapter in JP and EP.Other characterization tests, also harmonized, are provided in Biotechnology-Derived Articles—Amino Acid Analysis 1052, Biotechnology-Derived Articles—Capillary Electrophoresis 1053, … Where it is directed in the assay of Tablets to “weigh and finely powder not fewer than” a given number, usually 20, of the Tablets, it is intended that a counted number of Tablets shall be weighed and reduced to a powder. Conversely, where an automated procedure is given in the monograph, manual procedures employing the same basic chemistry are recognized as being equivalent in their suitability for determining compliance. However, Pharmacopeial standards and procedures are interrelated; therefore, where a difference appears or in the event of dispute, only the result obtained by the procedure given in this Pharmacopeia is conclusive. Where the definition in a monograph states the tolerances as being “calculated on the dried (or anhydrous or ignited) basis,” the directions for drying or igniting the sample prior to assaying are generally omitted from the, Throughout a monograph that includes a test for, Unless otherwise directed in the test or assay in the individual monograph or in a general chapter, USP Reference Standards are to be dried before use, or used without prior drying, specifically in accordance with the instructions given in the chapter. This includes the use of precautionary measures, protective equipment, and work practices consistent with the chemicals and procedures used. This difference in labeling the Standards is in effect only temporarily, and eventually all vials will bear the same title. 1 UNITS 2S (USP34) Table 1. The United States Pharmacopeia is the coordinating pharmacopeia in the efforts toward international harmonization of the specifications provided in this general test chapter. As the group of General Chapters evolves, General Chapter <111> will remain 13 in modified form. Two general methods are employed, the cylinder-plate or “plate” assay and the turbidimetric or “tube” assay. The aim of this chapter is to present a concise account of biometrical procedures for the USP bioassays. Preservation, Packaging, Storage, and Labeling, Description and Relative Solubility of USP and NF Articles. Otherwise an appropriate validated procedure is to be employed. The procedures described in the Identification, Control, and Quantification of Residual Solvents section of this General Chapter are to be applied wherever possible. Apply these methods, where indicated, in the testing of the appropriate dosage forms. Unless specifically Official text is text contained in USP and NF, including exempted elsewhere in a compendium, the identity, monographs, general chapters, and these General Notices. Instead, the AVRs are visual images used by analysts to compare certain test articles to ensure that they meet compendial requirements and are incorporated by reference into the monograph. An expression such as “(20:5:2)” means that the respective numbers of parts, by volume, of the designated liquids are to be mixed, unless otherwise indicated. Tests suitable for detecting and quantitating unlabeled impurities, when present as the result of process change or other identifiable, consistent occurrence, shall be submitted to the USP for inclusion in the individual monograph. The distribution of controlled substances is subject to the regulations and licensing provisions of the Drug Enforcement Administration of the Department of Justice. Otherwise, the impurity shall be identified, preferably by name, and the amount listed under the heading, Categories of drug substances excluded from. The volume of the suspension inoculum used is between 0.5% and 1.0% of the volume of the product. Unless a Reference Standard label states a specific potency or content, the Reference Standard is taken as being 100.0% pure for compendial purposes. The framework within which the results from a compendial test are interpreted is clearly outlined in Test Results, Statistics, and Standards under General Notices and Requirements. is advised to consult USP General Chapters Chromatog- raphy h 621 i ( 4 ), Titrimetry h 541 i ( 5 ), Spectrophotometry and Light-Scattering h 851 i ( 6 ), and books on analytical 130 〈171〉 Vitamin B12 Activity Assay / Biological Tests USP 35 cautions to maintain uniformity of sterilizing and cooling conditions throughout the assay, since packing tubes too Chemical Tests and closely in the autoclave, or overloading it, may cause varia-tion in the heating rate. Specific requirements for chromatographic procedures for drug substances and dosage forms, including adsorbent and developing solvents, are … The following ion chromatographic general procedure is provided for the determination of citric acid/citrate and phosphate in compendial articles, when specified in the individual monographs. The Current Good Manufacturing Practice regulations [21 CFR 211.194(a)] require that test methods, which are used for assessing compliance of pharmaceutical products with … This general chapter contains test methods for propellants, pressurized topical aerosols, nasal sprays, metered-dose inhalers, and propellant-free dry powder inhalers used to aerosolize, or to aerosolize and meter, doses of powders for inhalation. Application of Content Uniformity (CU) and Weight Variation (WV) Tests for Dosage Forms Dose & Ratio of Change to read: Drug Substance ≥25 <25 This general chapter is harmonized with the correspond-mg mg or ing texts of the European Pharmacopoeia and the Japanese Dosage and <25% Pharmacopoeia. Apparatus Suitability Test— Individually test 1 tablet of the USP Dissolution Calibrator, Disintegrating Type and 1 tablet of USP Dissolution Calibrator, Nondisintegrating Type, according to the operating conditions specified. HCPs can also have a direct effect on the quality of the product itself. 905 U nifo rm it y o f D o s a ge U nit s , USP 27 page 2396 and page 1587 of PF 28(5) [Sept.–Oct. USP Reference Standards are established and released under the authority of the USPC Board of Trustees upon recommendation of the USP Reference Standards Committee, which passes on the selection and suitability of each lot. Confusion of compendial standards with release tests and with statistical sampling plans occasionally occurs. [DRUG] Injection—Liquid preparations that are drug General Requirements for substances or solutions thereof. Automated procedures employing the same basic chemistry as those assay and test procedures given in the monograph are recognized as being equivalent in their suitability for determining compliance. Uses Chemical Tests and Assays Colorimetric Solutions 〈227〉 4-Aminophenol in Acetaminophen-Contain- Colorimetric Solutions Introduction, 5749 ing Drug Products, 6141 1. Two columns appear in the Catalog to identify the current official lots. An expression such as “(1 in 10)” means that 1 part. The result of the assay is then related to the amount of active ingredient per Tablet by multiplying this result by the average Tablet weight and dividing by the weight of the portion taken for the assay. Many Pharmacopeial tests and assays are based on comparison of a test specimen with a USP Reference Standard. General Chapters 1. To serve its intended purpose, each USP Reference Standard must be properly stored, handled, and used. General Chapters Butylated Hydroxytoluene (new), 2341 Copper Sulfate Pentahydrate (new), 2348 Cupric Nitrate, 2348 1,1-Cyclobutanedicarboxylic Acid (new), 2349 General Tests and Assays Hydroxypropyl Cellulose (new), 2364 Isonicotinic Acid, 2366 ... USP Reference Standards ASSAY