Compendia specifications

Label claims for tocopherol levels in preparations can be based on milligrams or International Units. Only the RRR or all-rac-International Units ate also used in some reference books and compendia, eg. Food Chemicals Codex (40,53), which is of particular importance for specifications for food fortification. 

Citric acid specifications are defined in a number of compendia including Vood Chemicals Codex (FCC), United States Pharmacopeia (USP), British Pharmacopeia (BP), European Pharmacopeia (EP), and Japanese Pharmacopeia (fP). 

Specific gravity is the ratio of the density of a substance to the density of water, the values for both substances being determined at the same temperature or at another specified temperature. For practical purposes, it may be defined as the ratio of the mass of a substance to the mass of an equal volume of water at the similar temperature. The official pharmaceutical compendia uses 25°C to express specific gravity. 

Technical information based on in vivo standards and specifications are generally incorporated in various official compendia. Hence, in order to record a legitimate assessment of bioavailability, in vivo test is an absolute necessity and the relative data obtained therefrom should form an integral part of the standard specifications in the offcial standard. 

A large number of miscellaneous characteristics are usually included in many official compendia to ascertain the purity, authenticity and identification of drugs—including sulphated ash, loss on drying, clarity and colour of solution, presence of heavy metals and specific tests. 

In fact, certain known impurities are present in a number of pharmaceutical substances. The presence of such impurities may be carried out by performing prescribed specific tests in various official compendia in order to ascertain their presence within the stipulated limits. 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

Once the appropriate dissolution conditions have been established, the method should be validated for linearity, accuracy, precision, specificity, and robustness/ruggedness. This section will discuss these parameters only in relation to issues unique to dissolution testing. All dissolution testing must be performed on a calibrated dissolution apparatus meeting the mechanical and system suitability standards specified in the appropriate compendia. 

The amount and level of contaminants or impurities in water for pharmaceutical purpose depend on its use. Since water is used in all industries and scientific work, international and national standard authorities have established water quality parameters for all types of applications. Health-related water standards are given by organizations such as the World Health Organization (WHO) [2], the Environmental Protection Agency (EPA) [3], and the American Society for Testing and Materials Standards (ASTM) [4] in the United States and by pharmacopeial compendia when the aim is specifically related to water for pharmaceutical products for human and veterinary consumption. 

Several officially recognized compendia describe specifications for components and finished product (e.g., U.S. Pharmacopeia, Food Chemicals Codex, British Pharmacopeia, and European Pharmacopeia). These specifications have been established by an advisory board to each compendium and represent the views of many manufacturers and government based on a history of the component or product. Such specifications are reviewed and updated as the need arises when new information becomes available. These compendia are very useful and should always be used as a guide whenever possible. In the case of the USP, for example, if a monograph exists for a component or product, U.S. drug manufacturers are required to satisfy those specifications as a minimum requirement. 

Sometimes compendia do not contain a monograph for the specific item that we are interested in. We can use the compendia as guides, following the specifications established for similar items. Then we must use our judgment to establish parameters that the material should be tested for based on our knowledge of the chemistry of the material. The next step is methods development, to derive a test procedure that enables us to measure each parameter. By testing different lots of the material we can establish a specification for the parameter. This work... 

Describe, as with the drug substance, the acceptable specifications for the drug product and the test methods used to assure the specifications. Cite any official compendia. 

For specific inquiries from industry, CDER s Compendia Operations can be called at (301) 594-0104. 

Optical rotation has the dual advantages of historical use and widespread recognition in the compendia. For an enantiopure material, it defines its configuration when used in conjunction with other valid chemical tests. However, optical rotation has been used ineffectively when the primary analytical goal is the determination of stereochemical purity. The limits selected for the specification seem to be unrelated to the purity required by other methods. For example, the compendial monograph for naproxen requires that the drug substance meet a specification of "between -f-63.0 and -1-68.5"" in a chloroform solution. Based on the published specific rotation, this corresponds to a stereochemical purity of 95.5 to 103.7%, compared to the assay limits of 98.5 to 100,5%, determined by titration with sodium hydroxide (5). 

If averaging is employed, OOS results must be included along with within-specification findings, unless they may be discarded by an approved statistical outlier test (either approved in the compendia or in the IND). 

It is also necessary to consider the regulatory status of excipients and any country-specific requirements or constraints. The U.S. and Japanese regulatory agencies publish lists of excipients used in medicinal pro-ducts. The materials listed in these compendia can generally be considered suitable for administration by the route for which they are already being used. For materials with no history of previous use, evidence must be provided that they do not compromise patient safety nor induce any other undesirable effects. 

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