In-house standard

Manufacturing, analytical, and quaUty control procedures are thus estabhshed. Specifications for taw and in-process materials, as well as for final products per USP/NF and in-house standards are also determined. Process and formula vaUdation assures that each technological procedure in manufacture accomplishes its purpose most efficiently, eg, blending times for powdered mixtures in tableting, and that each formula ingredient is present in optimal concentrations (12). Thus, it serves to ensure process control (qv), reproducibiUty, and content uniformity. 

Nothing Else Available When there is no commercial working standard, and there is a CRM available, many scientists will not bother to spend the time and effort required to characterize an in-house standard. 

International or in-house standards in combination with fundamental parameters software, lead to the same accuracy as conventional analysis using regression analysis of standards. Provided that accurate standards are available, the main factors that determine the accuracy of XRF are the matrix absorption correction and (in the case of EDXRF) the spectrum evaluation programme, i.e. correction for spectral overlap and background. 

As well as the various national standards and codes, the larger design organisations will have their own (in-house) standards. Much of the detail in engineering design work is routine and repetitious, and it saves time and money, and ensures a conformity between projects, if standard designs are used whenever practicable. 

Sample numbers have been randomised to minimise regional bias, help separate false from true anomalies and obtain meaningful estimates of the variance of duplicates. Field duplicates, analytical duplicates, in-house standards and certified reference materials are introduced at regular intervals in the analytical streams. 

Because of the cost of primary standards, it is normal to use them very sparingly (certainly not as calibration standards), but to include them as unknowns in the analytical run as a measure of the quality of the analysis (see QA, below). Even so, this becomes prohibitively expensive, and it is common to use materials which can be included in each analysis, which may not be fully certified, but whose values can be related to a primary standard. These are often referred to as in-house standards, although they may be more generally available. They can be home-made, providing sufficient attention has been paid to homogenizing the material thoroughly. A simple example is... 

An outline laboratory QA procedure would need to include the following. In addition to the use of freshly made synthetic calibration standards, in-house standards, internationally recognized reference materials, and method blanks, as described above, it should include ... 

The development of in-house standards for impurities is often necessary due to the unavailability of a compendial impurity standard. The process of developing an in-house standard is the topic for another publication. However, there are aspects that should be addressed herein. These include the establishment and maintenance of an impurity standard. The establishment of an impurity standard is a difficult process. The method that has been developed to monitor the impurity level of the drug substance is often inappropriate or insufficient to monitor the purity of the standard. The process described above to develop a procedure to monitor impurities in the drug substance must be re-evaluated... 

To check traeness against an alternative method, the same sample or samples are analysed by the two methods and the two series of results are compared for a statistically significant difference. The samples may be CRM s, in-house standards, or simply typical samples. In the case where only one sample is used, the two methods are employed to make ten measurements. 

Where practical, the calibration standards used for production and quality assurance measurement equipment shall be traceable to the national standards of the National Bureau of Standards, Department of Commerce. If national standards are not practical for the parameter being measured, an independent reproducible standard shall be used. If no applicable standard exists, an in-house standard shall be developed and used. 

Standard rubbers are given in several of the test method standards. Some are purely for normalizing the abrasive and have no particular service relevance. Others, such as those based on a tyre tread compound or a shoe sole type material, have the advantage of a practical significance as well as a normalizing role. There is no reason at all why, for a particular investigation, an in-house standard representative of the type of material being evaluated should not be used. 

If no applicable standard exists, the manufacturer shah establish and maintain an in-house standard. 

Calibration standards. Calibration standards used for inspection, measuring and test equipment shall be traceable to national or international standards. If national or international standards are not practical or available, the manufacturer shall use an independent reproducible standard. If no applicable standard exists, the manufacturer shall establish and maintain an in-house standard. 

Gas analytical instruments for vehicle exhaust emission surveillance, evidential breath alcohol analysis in road traffic and calorific value determination of fuel gases are subject to legal control and require type approval and initial and subsequent verification. The national standards required in this part of gas analysis are provided by BAM. PTB uses in-house standards prepared by dynamic blending to ensure traceability of its type approval... 

Rieger and Ballschmiter [43] developed a low resolution method for PCA analyses, based on GC/ECNI-MS in the SIM mode. Their method of quantifying PCAs in environmental samples was based on a triangulation method previously developed in their laboratory for the analysis of toxaphene [56], For PCAs, typically four ions,known to be prominent in the external standard, were monitored in separate injections of a known amount of standard and in the sample, and the areas of the broad PCA peak were then compared. The choice of external standard used was based on pattern matching, i.e., visually comparing the elution time and signal structure of the sample to those of a number of in-house standards [57],... 

XML files to and from the application tools by mediating between the in-house standard and the internal data models of the application tools. 

The myriad of government mandates has required plastics for most industrial applications to be self-extinguishing and/or fire retardant. The plastics industry has been responsive to these mandates as well as those imposed by in-house standards of many... 

OTHER AREAS. Those that can lead to approval delays include (1) use of instrumentation not commercially available and the absence of a detailed description of the components and assembly, (2) use of single source specifications to permit duplication, (3) use of specialized tools or equipment not available to the FDA chemists for sample preparation, (4) use of an in-house standard or other noncommercial reagent, and (5) failure to provide a system suitability test on chromatographic procedures. 

Geological samples In-house standard, CANMET standards Au Ag Pd Heat with aqua regia/HCl [WDC] Treat with activated carbon, digest with HNO3/HCIO4, aspirate into A/A flame [FAAS] [WDC-SEP/ CONC-FAAS] Chakrapani et al. (2001)... 

Reference standards are available in the form of official reference standards. Secondary standards are established by the application of appropriate tests and checks at regular intervals to ensure standardization. All in-house standards are based on official reference standards when available. All reference standards are stored and used in a manner that will not adversely affect their quality. Adequate records are maintained. 

The content of this Guide is addressed to the manufacturers of ethical and proprietary medicines. The Guide has, however, no legal standing. The responsibility for GMP lies with the individual company to comply with Act 101 of 1965 as amended and to satisfy the Medicines Control Council during plant inspections. Nevertheless, companies may impose stricter in-house standards. Alternative measures capable of achieving the requirements are also acceptable. 

The bench top analyzer was first calibrated using commercial gravimetrically based diesel standards. Two sets of commercial diesel standards and a set of in-house prepared standards were used to generate three different calibration curves for comparison. The first set of standards, made from No. 2 diesel (Vendor A), included sulfur concentration levels of 0 ppm (blank), 5 ppm, 10 ppm, 100 ppm, 500 ppm, 1000 ppm, and 3000 ppm. The second set, made from a synthetic diesel fuel matrix (Vendor B), included sulfur levels of close to 0 ppm (blank), 20 ppm, 50 ppm, 100 ppm, 200 ppm and 500 ppm. The in-house standards were made by mixing different ratios of decalin and n-butyldisulfide (CgHigS) gravimetrically with resulting sulfur concentration levels of close to 0 ppm (blank), 10 ppm, 48.6 ppm, 87.6 ppm, 320 ppm, and 946 ppm. The measured sulfur fluorescent X-ray intensity, in coimts, for each standard is listed in Table 1. 

Therapeutic proteins are manufactured by complicated processes, and all steps in production, purihcation, and formulation may inhuence the biological and cli-nicial properties of the hnal product. The different steps are, therefore, carefully monitored by analytical methods using in-house standards. These analytical methods have, in part, been developed (or at least rehned) for each specihc product. For many products and especially the hrst for which the patents will expire shortly, the production process has undergone continuous improvement based on manufacturing and clinical experience. 

The features of a particular biopharmaceutical are the result of the basic characteristics of the molecule such as amino acid sequence and three-dimensional structure as well as the specihc production, purihcation, formulation, and storage conditions (Box 12.4-2). To produce a biopharmaceutical of constant required quality, a company also needs the experience and the in-house standards to apply the methods used to analyze the structure of a given product. There are various guidelines of the European Medicine Evaluation Agency, the Food and Drug Administration, the Japanese Ministry of Health and Welfare, and the ICH, which require manufacturers to show that they control the production process and are capable of reproducibly manufacturing batches that not only meet product specih-cations, but also conform to the dehnition of the product as established through full characterization. Modihcations of the established process are only accepted if the manufacturer can show that the product of the new process is comparable with the initially manufactured product. Comparability studies include revalidation of... 

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