Laboratory control standards

Matrix spike standard solutions and laboratory control standards which are added to one sample per batch to assess matrix effects. 

The international normalized ratio (INR) is a method to standardize repotting of the prothrombin time, using the formula, INR = (PTpatie t/PTcontroi)ISI, where PT indicates the prothrombin times (for the patient and the laboratory control), and ISI indicates the international sensitivity index, a value that varies, depending upon the thromboplastin reagent and laboratory instrument used to initiate and detect clot formation, respectively. 

Any deviation from the written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms shall be recorded and justified. 

The backbone of the laboratory control system rests on the philosophy used to establish sound and appropriate specifications, standards, and test procedures to ensure drug product quality. Some of the components of this section of the law are as follows ... 

Because of the status of the CAC described above, the work that it has carried out in the area of laboratory quality assurance must be carefully considered. One of the CAC Committees, the Codex Committee on Methods of Analysis and Sampling (CCMAS), has developed criteria for assessing the competence of testing laboratories involved in the official import and export control of foods. These were recommended by the Committee at its 21st Session in March 19979 and adopted by the Codex Alimentarius Commission at its 22nd Session in June 1997 10 they mirror the EU recommendations for laboratory quality standards and methods of analysis. The guidelines provide a framework for the implementation of quality assurance measures to ensure the competence of testing laboratories involved in the import and export control of foods. They are intended to assist countries in then-fair trade in foodstuffs and to protect consumers. 

The model systems eventually must be compared against natural habitats. Although the results of the controlled, standardized laboratory tests give important basic and practical information (as do those from terrestrial metabolism chambers), there is no reason to believe that they represent quantitatively the behavior of the animals in Nature ... 

The accuracy of an analysis can be determined by several procedures. One common method is to analyze a known sample, such as a standard solution or a quality control check standard solution that may be available commercially, or a laboratory-prepared standard solution made from a neat compound, and to compare the test results with the true values (values expected theoretically). Such samples must be subjected to all analytical steps, including sample extraction, digestion, or concentration, similar to regular samples. Alternatively, accuracy may be estimated from the recovery of a known standard solution spiked or added into the sample in which a known amount of the same substance that is to be tested is added to an aliquot of the sample, usually as a solution, prior to the analysis. The concentration of the analyte in the spiked solution of the sample is then measured. The percent spike recovery is then calculated. A correction for the bias in the analytical procedure can then be made, based on the percent spike recovery. However, in most routine analysis such bias correction is not required. Percent spike recovery may then be calculated as follows ... 

We are starting with the case where we have a control sample that covers the whole analytical process inclnding all sample preparation steps. The matrix of the control sample is similar to that of the routine samples. Then the standard deviation of the analysis of this sample (under between-batch conditions) can be used directly as an estimate for the reproducibility within the laboratory. The standard deviation can be taken directly from a control chart for this control sample (see chapterl3). In the table two examples are shown for different concentration levels. 

Environmental Protection Agency. Toxic substances control Good laboratory practice standards Final rule. Fed Reg 48 53921-53944, 1983 Environmental Protection Agency. Pesticides program Good laboratory practice standards Final rule. Fed Reg 48 53945-53969, 1983. 

Environmental Protection Agency. Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Good laboratory practice standards, proposed rule. Fed Reg 52 48920-48933, 1987 Environmental Protection Agency. Toxic Substances Control. Act (TSCA) Good laboratory practice standards, proposed rule. Fed Reg 52 489933-48946, 1987. 

Quality control standards have been developed for the new petroleum weed killers and laboratory techniques have been worked out tor testing and establishing the suitability of a given petroleum fraction for a specific herbicidal use. Although attempts to correlate herbicidal action with physical and chemical tests have not been entirely successful, the use of additional specific t ts to determine the chemical composition of the fraction has served as an indicator of toxicity in the specific composition under study. 

The cGMPs require manufacturers to have adequately equipped manufacturing facilities, adequately trained personnel, precisely controlled manufacturing processes, appropriate laboratory controls, complete and accurate records and reports, appropriate finished product examination, and so on. Current GMPs are not best practices rather, they establish threshold or minimum standards which must be satisfied in order for a pharmaceutical manufacturing operation to be compliant. 

Laboratory controls do not include the establishment of scientifically sound and appropriate specifications/standards/sampling plans/test procedures. 

In the United States GMP regulations [7] issues related to laboratory controls are covered in Subpart I, which consists of regulations 211.160,211.165,211.166,211.167, 211.170, 211.173, and 211.176. The contents of Subpart I is presented in Table 24. Regulation 211.160 states the requirements for the establishment of laboratory controls such as specifications, standards, sampling plans, and test procedures. Furthermore, it covers the requirements stated for the calibration of instruments, apparatus, gauges, and recording devices. Regulation 211.165 states the require-... 

In our laboratory, control values that fall within 2 standard deviations of the mean are considered acceptable and require no further action. Any control values that are either greater than 2 standard deviations or trends require review by a laboratory director. The laboratory director decides whether the analysis of the complete batch or of specific samples needs to be repeated and initiates troubleshooting. 

Laboratory controls should include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures to ensure that raw materials and containers conform to established standards of quality and purity. Specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, including any minor changes, should be updated by the appropriate organizational unit and reviewed and approved by the QC unit. Laboratory controls should be followed and documented at the time of performance. Deviations from written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms should be documented and justified. 

Routine or field laboratories involved in the ANP are controlled in each Member State by at least one National Reference Laboratory (NRL) designated by the National Government (51, 52). National Laboratories are in turn responsible for the standards maintained in any other laboratories in their own country that are involved in the National Sampling Plan program. National Reference laboratories coordinate standards and methods of analysis for each group of residues, and may undertake work on all or limited classes of the veterinary drug areas listed in Directive 86/469/EEC. 

Every analytical laboratory, governmental, private, or university, has a standard set of procedures that provide both general and specific information to laboratory members. These fall into certain categories, including the laboratory s standard operating procedures (SOPs), quality assurance/quality control manuals (QA/QC manuals), procedural manuals, analytical method files, and laboratory information management systems... 

Final Rule for Good Laboratory Practice Standards under the Toxic Substances Control Act. 40 CFR Part 792. Federal Register, 48 pp 53922-53944, November 29, 1983. 

Federal Insecticide, Etmgicide and Rodenticide Act (FIFRA) and Toxic Substances Control Act (TSCA) Good Laboratory Practice Standards Proposed Rules, Fed. Reg., 52 48920, December 28, 1987. 

Another tool that enables us to evaluate analytical accuracy of organic analyses is surrogate standards. These are compounds that do not naturally occur in the environment and that are similar in chemical nature and behavior to target analytes. In organic compound analysis, known amounts of surrogate standards are added to each sample prior to extraction. The comparison of surrogate standard recoveries to laboratory control limits permits the laboratory to monitor the efficacy of extraction and to measure the accuracy of analysis for each individual sample. 

Analysis of surrogate standards and laboratory control samples to measure analytical accuracy... 

Laboratory QC data are classified as batch QC data and individual sample QC data. For all types of analysis, batch QC data originate from laboratory blanks, laboratory control samples, matrix spikes, and laboratory duplicates. Individual sample QC data in organic compound analysis are obtained from surrogate and internal standard recoveries. Matrix interference detection techniques (serial dilution tests, postdigestion spike additions, and MSA tests) are the source for individual sample QC checks in trace element analysis. (Chapter 4.4.4.5 addresses the trace element matrix interference detection techniques and the associated acceptance criteria.)... 

Similar to LCS recoveries, surrogate standard recoveries should be monitored by the laboratory and plotted as control charts. The EPA recommends the use of in-house laboratory control limits for surrogate standards recoveries for all organic compound analyses (EPA, 1996a). The exception is the CLP SOW, which specifies these limits for soil and water analysis. Unless affected by matrix interferences, surrogate standard recoveries normally have relatively narrow control limits, 65-135 percent for most organic compound analysis. (Many laboratories, however, default to arbitrary limits of 50-150 percent for GC analyses, instead of using statistical control limits.)... 

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